Home › Urolithiasis

Urolithiasis

Full Text Guidelines

Summary of Changes

Scientific Publications & Appendices

Pocket Guidelines

1.INTRODUCTION

1.1.Aims and scope

The European Association of Urology (EAU) Urolithiasis Guidelines Panel has prepared these guidelines to help urologists assess evidence-based management of stones/calculi in the urinary tract and incorporate recommendations into clinical practice. This document covers most aspects of the disease, which is still a cause of significant morbidity despite technological and scientific advances. The Panel is aware of the geographical variations in healthcare provision. Management of bladder stones has previously not been addressed in these guidelines; however, as of the 2019 edition, bladder stones are dealt with in a new, separate, guideline authored by the same guideline group.

It must be emphasised that clinical guidelines present the best evidence available to the experts but following guideline recommendations will not necessarily result in the best outcome. Guidelines can never replace clinical expertise when making treatment decisions for individual patients, but rather help to focus decisions - also taking personal values and preferences/individual circumstances of patients into account.

Guidelines are not mandates and do not purport to be a legal standard of care.

1.2.Panel composition

The EAU Urolithiasis Guidelines Panel consists of an international group of clinicians with particular expertise in this area. All experts involved in the production of this document have submitted potential conflict of interest statements, which can be viewed on the EAU, website Uroweb: http://uroweb.org/guideline/urolithiasis/.

1.3.Available publications

A quick reference document (Pocket guidelines) is available, both in print and as an app for iOS and Android devices. These are abridged versions, which may require consultation together with the full text versions. Also a number of scientific publications are available [1-3]. All documents can be accessed through the EAU website: http://uroweb.org/guideline/urolithiasis/.

1.4.Publication history and summary of changes

1.4.1.Publication history

The EAU Urolithiasis Guidelines were first published in 2000. This 2019 document presents a limited update of the 2018 version.

1.4.2.Summary of changes

The literature for the entire document has been assessed and updated, wherever relevant (see Methods section below).

For 2019, conclusions and recommendations have been rephrased and added to throughout the current document, including the sections on high-risk stone formers, anti-coagulation and paediatric urolithiasis. Updated summaries of evidence and recommendations include the following:

3.4.1.1 Summary of evidence and guidelines for the management of renal colic

Recommendation	Strength rating
Offer opiates (hydromorphine, pentazocine or tramadol) as a second choice.	Weak

3.4.5.1 Summary of evidence and guidelines for SWL

Summary of evidence	LE
Proper acoustic coupling between the cushion of the treatment head and the patient’s skin is important.	2
Careful imaging control of localisation of stone contributes to outcome of treatment.	2a
Careful control of pain during treatment is necessary to limit pain-induced movements and excessive respiratory excursions.	1a
Antibiotic prophylaxis is recommended in the case of internal stent placement, infected stones or bacteriuria.	1a

3.4.8.4 Stone composition

Recommendations	Strength rating
Consider the stone composition before deciding on the method of removal, based on patient history, former stone analysis of the patient or Hounsfield unit (HU) on unenhanced computed tomography (CT).	Strong

3.4.11.1 Summary of evidence and guidelines for laparoscopy and open surgery

Recommendations	Strength rating
Offer laparoscopic or open surgical stone removal in rare cases in which shock wave lithotripsy (SWL), retrograde or antegrade ureteroscopy and percutaneous nephrolithotomy fail, or are unlikely to be successful.	Strong

.3.4.14.4.1 Summary of evidence and guidelines for the management of stones in patients with transplanted kidneys

Summary of evidence	LE
Shock wave lithotripsy for small calyceal stones is an option with minimal risk of complication, but localisation of the stone can be challenging and SFRs are poor.	4

3.4.15.8 Summary of evidence and guidelines for the management of stones in children

Summary of evidence	LE
In children, the indications for SWL, URS and PNL are similar to those in adults.	1b

Recommendations	Strength rating
Offer children with single ureteral stones less than 10 mm shock wave lithotripsy (SWL) if localisation is possible as first line option.	Strong
Ureteroscopy is a feasible alternative for ureteral stones not amenable to SWL.	Strong
Offer children with renal stones with a diameter of up to 20 mm (~300 mm2) shock wave lithotripsy.	Strong
Offer children with renal pelvic or calyceal stones with a diameter > 20 mm (~300 mm2) percutaneous nephrolithotomy.	Strong
Retrograde renal surgery is a feasible alternative for renal stones smaller than 20 mm in all locations.	Weak

3.GUIDELINES

3.1.Prevalence, aetiology, risk of recurrence

3.1.1.Introduction

Stone incidence depends on geographical, climatic, ethnic, dietary and genetic factors. The recurrence risk is basically determined by the disease or disorder causing the stone formation. Accordingly, the prevalence rates for urinary stones vary from 1% to 20% [8]. In countries with a high standard of life such as Sweden, Canada or the USA, renal stone prevalence is notably high (> 10%). For some areas an increase of more than 37% over the last 20 years has been reported [9-11]. There is emerging evidence linking nephrolithiasis to the risk of chronic kidney disease [12].

Stones can be stratified into those caused by: infection, or non-infectious causes, genetic defects [13]; or adverse drug effects (drug stones) (Table 3.1). See also section 3.2.

Table 3.1: Stones classified by aetiology*

Non-infection stones

Calcium oxalate

Calcium phosphate

Uric acid

Infection stones

Magnesium ammonium phosphate

Carbonate apatite

Ammonium urate

Genetic causes

Cystine

Xanthine

2,8-Dihydroxyadenine

Drug stones

*See Section 4.4.2

3.1.2.Stone composition

Stone composition is the basis for further diagnostic and management decisions. Stones are often formed from a mixture of substances. Table 3.2 lists the most clinically relevant substances and their mineral components.

Table 3.2: Stone composition

Chemical name	Mineral name	Chemical formula
Calcium oxalate monohydrate	Whewellite	CaC2O4.H2O
Calcium oxalate dihydrate	Wheddelite	CaC2O4.2H2O
Basic calcium phosphate	Apatite	Ca10(PO4)6.(OH)2
Calcium hydroxyl phosphate	Carbonite apatite	Ca5(PO3)3(OH)
b-tricalcium phosphate	Whitlockite	Ca3(PO4)2
Carbonate apatite phosphate	Dahllite	Ca5(PO4)3OH
Calcium hydrogen phosphate	Brushite	CaHPO4.2H2O
Calcium carbonate	Aragonite	CaCO3
Octacalcium phosphate		Ca8H2(PO4)6.5H2O
Uric acid	Uricite	C5H4N4O3
Uric acid dehydrate	Uricite	C5H4O3-2H20
Ammonium urate		NH4C5H3N4O3
Sodium acid urate monohydrate		NaC5H3N4O3.H2O
Magnesium ammonium phosphate	Struvite	MgNH4PO4.6H2O
Magnesium acid phosphate trihydrate	Newberyite	MgHPO4.3H2O
Magnesium ammonium phosphate monohydrate	Dittmarite	MgNH4(PO4).H2O
Cystine		[SCH2CH(NH2)COOH]2
Xanthine
2,8-Dihydroxyadenine
Proteins
Cholesterol
Calcite
Potassium urate
Trimagnesium phosphate
Melamine
Matrix
Drug stones	• Active compounds crystallising in urine • Substances impairing urine composition (Section 4.11)
Foreign body calculi

3.1.3.Risk groups for stone formation

The risk status of stone formers is of particular interest because it defines the probability of recurrence or regrowth, and is imperative for pharmacological treatment.

About 50% of recurrent stone formers have just one lifetime recurrence [10,14]. Highly recurrent disease is observed in slightly more than 10% of patients. Stone type and disease severity determine low- or high risk of recurrence (Table 3.3) [15,16].

Table 3.3: High-risk stone formers [15-31]

General factors

Early onset of urolithiasis (especially children and teenagers)

Familial stone formation

Brushite-containing stones (CaHPO4.2H2O)

Uric acid and urate-containing stones

Infection stones

Solitary kidney (the kidney itself does not particularly increase the risk of stone formation, but prevention of stone recurrence is of more importance)

Diseases associated with stone formation

Hyperparathyroidism

Metabolic syndrome

Nephrocalcinosis

Polycystic kidney disease (PKD)

Gastrointestinal diseases (i.e., jejuno-ileal bypass, intestinal resection, Crohn’s disease, malabsorptive conditions, enteric hyperoxaluria after urinary diversion) and bariatric surgery

Increased levels of vitamin D

Sarcoidosis

Spinal cord injury, neurogenic bladder

Genetically determined stone formation

Cystinuria (type A, B and AB)

Primary hyperoxaluria (PH)

Renal tubular acidosis (RTA) type I

2,8-Dihydroxyadeninuria

Xanthinuria

Lesch-Nyhan syndrome

Cystic fibrosis

Drug-induced stone formation (see Table 4.11)

Anatomical abnormalities associated with stone formation

Medullary sponge kidney (tubular ectasia)

Ureteropelvic junction (UPJ) obstruction

Calyceal diverticulum, calyceal cyst

Ureteral stricture

Vesico-uretero-renal reflux

Horseshoe kidney

Ureterocele

Environmental factors

High ambient temperatures

Chronic lead and cadmium exposure

3.2.Classification of stones

Urinary stones can be classified according to size, location, X-ray characteristics, aetiology of formation, composition, and risk of recurrence [10,32-34].

3.2.1.Stone size

Stone size is usually given in one or two dimensions, and stratified into those measuring up to 5, 5-10, 10-20, and > 20 mm in largest diameter.

3.2.2.Stone location

Stones can be classified according to anatomical position: upper, middle or lower calyx; renal pelvis; upper, middle or distal ureter; and urinary bladder. Treatment of bladder stones is not discussed in these guidelines.

3.2.3.X-ray characteristics

Stones can be classified according to plain X-ray appearance [kidney-ureter-bladder (KUB) radiography] (Table 3.4), which varies according to mineral composition [34]. Non-contrast-enhanced computed tomography (NCCT) can be used to classify stones according to density, inner structure and composition, which can affect treatment decisions (Section 3.3) [32,34].

Table 3.4: X-ray characteristics

Radiopaque	Poor radiopacity	Radiolucent
Calcium oxalate dehydrate	Magnesium ammonium phosphate	Uric acid
Calcium oxalate monohydrate	Apatite	Ammonium urate
Calcium phosphates	Cystine	Xanthine
		2,8-Dihydroxyadenine
		Drug-stones (Section 4.11)

Stratification of stones according to aetiology, composition and risk of recurrence is addressed in Section 3.1.

3.3.Diagnostic evaluation

3.3.1.Diagnostic imaging

The most appropriate imaging modality will be determined by the clinical situation, which will differ depending on if a ureteral or a renal stone is suspected.

Standard evaluation includes a detailed medical history and physical examination. Patients with ureteral stones usually present with loin pain, vomiting, and sometimes fever, but may also be asymptomatic [35]. Immediate evaluation is indicated in patients with solitary kidney, fever or when there is doubt regarding a diagnosis of renal colic. Ultrasound (US) should be used as the primary diagnostic imaging tool, although pain relief, or any other emergency measures, should not be delayed by imaging assessments. Ultrasound is safe (no risk of radiation), reproducible and inexpensive. It can identify stones located in the calices, pelvis, and pyeloureteric and vesico-ureteral junctions (US with filled bladder), as well as in patients with upper urinary tract (UUT) dilatation. Ultrasound has a sensitivity of 45% and specificity of 94% for ureteral stones and a sensitivity of 45% and specificity of 88% for renal stones [36,37].

The sensitivity and specificity of KUB is 44-77% [38]. Kidney-ureter-bladder radiography should not be performed if NCCT is considered [39]. However, KUB is helpful in differentiating between radiolucent and radiopaque stones and should be used for comparison during follow-up.

3.3.1.1.Evaluation of patients with acute flank pain/suspected ureteral stones

Non-contrast-enhanced computed tomography (CT) has become the standard for diagnosing acute flank pain, and has replaced intravenous urography (IVU). Non-contrast-enhanced CT can determine stone diameter and density. When stones are absent, the cause of abdominal pain should be identified. In evaluating patients with suspected acute urolithiasis, NCCT is significantly more accurate than IVU [40].

Non-contrast-enhanced CT can detect uric acid and xanthine stones, which are radiolucent on plain films, but not indinavir stones [41]. Non-contrast-enhanced CT can determine stone density, inner structure of the stone, skin-to-stone distance and surrounding anatomy; all of which affect selection of treatment modality [34,42-44]. The advantage of non-contrast imaging must be balanced against loss of information on renal function and urinary collecting system anatomy, as well as higher radiation dose [45-48].

Radiation risk can be reduced by low-dose CT, which may, however, be difficult to introduce in standard clinical practice [49-51]. In patients with a body mass index (BMI) < 30, low-dose CT has been shown to have a sensitivity of 86% for detecting ureteral stones < 3 mm and 100% for calculi > 3 mm [52]. A MA of prospective studies [51] has shown that low-dose CT diagnosed urolithiasis with a pooled sensitivity of 93.1% (95% CI: 91.5-94.4), and a specificity of 96.6% (95% CI: 95.1-97.7%). Dual-energy CT can differentiate uric acid containing stones from calcium-containing stones [53].

3.3.1.2.Radiological evaluation of patients with renal stones

Intravenous urography can provide information about renal function, the anatomy of the collecting system and the level of an obstruction, while CT allows for rapid 3D data acquisition including information on stone size and density, skin-to-stone distance and surrounding anatomy, but at the cost of increased radiation exposure. Low-dose and ultra-low-dose protocols seem to yield comparable results as standard-dose protocols with the exception of detection of very small stones or stones in obese patients [51,52,54].

A small randomised study showed that in supine percutaneous antegrade ureteroscopy (PNL),
pre-operative planning using CT, compared to IVU, resulted in easier access and shorter operating times [55].

In case stone removal is planned and the renal collecting system needs to be assessed, a contrast study should be performed [56].

3.3.1.3.Summary of evidence and guidelines for diagnostic imaging

Summary of evidence	LE
Non-contrast-enhanced CT is used to confirm stone diagnosis in patients with acute flank pain, as it is superior to IVU.	1a
Enhanced CT enables 3D reconstruction of the collecting system, as well as measurement of stone density and skin-to-stone distance.	2a

Recommendations	Strength rating
With fever or solitary kidney, and when diagnosis is doubtful, immediate imaging is indicated.	Strong
Following initial ultrasound assessment, use non-contrast-enhanced computed tomography to confirm stone diagnosis in patients with acute flank pain.	Strong
Perform a contrast study if stone removal is planned and the anatomy of the renal collecting system needs to be assessed.	Strong

3.3.2.Diagnostics - metabolism-related

Each emergency patient with urolithiasis needs a succinct biochemical work-up of urine and blood besides imaging. At this point, no distinction is made between high- and low-risk patients for stone formation.

3.3.2.1.Basic laboratory analysis - non-emergency urolithiasis patients

Biochemical work-up is similar for all stone patients. However, if no intervention is planned, examination of sodium, potassium, C-reactive protein (CRP), and blood coagulation time can be omitted.

Only patients at high risk for stone recurrence should undergo a more specific analytical programme [16]. Stone-specific metabolic evaluation is described in Chapter 4.

The easiest method for diagnosing stones is by analysis of a passed stone using a validated method as listed below (see 3.3.2.3). Once the mineral composition is known, a potential metabolic disorder can be identified.

3.3.2.2.Analysis of stone composition

Stone analysis should be performed in all first-time stone formers.

In clinical practice, repeat stone analysis is needed in the case of:

recurrence under pharmacological prevention;
early recurrence after interventional therapy with complete stone clearance;
late recurrence after a prolonged stone-free period [57-59].

Patients should be instructed to filter their urine to retrieve a concrement for analysis. Stone passage and restoration of normal renal function should be confirmed.

The preferred analytical procedures are infrared spectroscopy (IRS) or X-ray diffraction (XRD) [60-62]. Equivalent results can be obtained by polarisation microscopy. Chemical analysis (wet chemistry) is generally deemed to be obsolete [60,63].

3.3.2.3.Guidelines for laboratory examinations and stone analysis [16,22,57,64]

Recommendations: basic laboratory analysis - emergency urolithiasis patients	Strength rating
Urine
Dipstick test of spot urine sample: • red cells; • white cells; • nitrite; • approximate urine pH; • urine microscopy and/or culture.	Strong
Blood
Serum blood sample: • creatinine; • uric acid; • (ionised) calcium; • sodium; • potassium; • blood cell count; • C-reactive protein.	Strong
Perform a coagulation test (partial thromboplastin time and international normalised ratio) if intervention is likely or planned.	Strong
Perform stone analysis in first-time formers using a valid procedure (X-ray diffraction or infrared spectroscopy).	Strong
Repeat stone analysis in patients presenting with: • recurrent stones despite drug therapy; • early recurrence after complete stone clearance; • late recurrence after a long stone-free period because stone composition may change.	Strong

3.3.3.Diagnosis in special groups and conditions

3.3.3.1.Diagnostic imaging during pregnancy

In pregnant women radiation exposure may cause non-stohastic (teratogenesis) or stohastic (carcinogenesis, mutagenesis) effects. Teratogenic effects are cumulative with increasing dose, and require a threshold dose (< 50 mGy are considered as safe) and depend on the gestation age (minimum risk prior to 8th week and after the 23rd week). Carcinogenesis (dose even < 10 mGy present a risk) and mutagenesis (500-1000 mGy doses are required, far in excess of the doses in common radiographic studies) get worse with increasing dose but they do not require a dose threshold and are not dependent on the gestational age [65].

There is no imaging modality that should be routinely repeated in pregnant women. Scientific societies and organisations agree on the safety of the diagnostic evaluation when US [66], X-ray imaging [67,68], and MRI [69,70] are used as and when indicated [71-77]. A radiographic procedure should not be withheld from a pregnant woman if the procedure is clearly indicated and doing so will affect her medical care.

It is generally recommended that an investigation resulting in an absorbed dose to the foetus of greater than 0.5 mGy requires justification.

Ultrasound (when necessary using changes in renal resistive index and transvaginal/transabdominal US with a full bladder) has become the primary radiological diagnostic tool when evaluating pregnant patients suspected of renal colic. However, normal physiological changes in pregnancy can mimic ureteral obstruction [73-75].

Magnetic resonance imaging can be used, as a second-line procedure, to define the level of urinary tract obstruction, and to visualise stones as a filling defect [72,77]. As 3 Tesla (T) MRI has not been evaluated in pregnancy, the use of 1.5T is currently recommended. The use of gadolinium is not routinely recommended in pregnancy to avoid toxic effects to the embryo.

For the detection of urolithiasis during pregnancy, low-dose CT is associated with a higher positive predictive value (95.8%), compared to MRI (80%) and US (77%). As per White et al. low-dose CT offers improved diagnostic accuracy that can avoid negative interventions such as ureteroscopy [78]. Although low-dose CT protocols reduce the radiation exposure, judicious use is currently recommended in pregnant women as a last-line option [73].

3.3.3.1.1.Summary of evidence and guidelines for diagnostic imaging during pregnancy

Summary of evidence	LE
Only low-level data exist for imaging in pregnant women supporting US and MRI.	3

Recommendations	Strength rating
Use ultrasound as the preferred method of imaging in pregnant women.	Strong
In pregnant women, use magnetic resonance imaging as a second-line imaging modality.	Strong
In pregnant women, use low-dose computed tomography as a last-line option.	Strong

3.3.3.2.Diagnostic imaging in children

Children with urinary stones have a high risk of recurrence; therefore, standard diagnostic procedures for high-risk patients apply, including a valid stone analysis (Section 3.1.3 and Chapter 4). The most common non-metabolic disorders facilitating stone formation are vesico-ureteral reflux (VUR), UPJ obstruction, neurogenic bladder, and other voiding difficulties [79].

When selecting diagnostic procedures to identify urolithiasis in children, it should be remembered that these patients might be uncooperative, require anaesthesia, and may be sensitive to ionising radiation [80-82]. Again, the principle of ALARA (As Low As Reasonably Achievable) should be observed.

Ultrasound
Ultrasound is the primary imaging technique [80] in children. Its advantages are absence of radiation and no need for anaesthesia. Imaging should include both the fluid-filled bladder with adjoining portion of the ureters, as well as the upper ureter [83-87]. Colour Doppler US shows differences in the ureteral jet [84] and resistive index of the arciform arteries of both kidneys, which are indicative of the grade of obstruction [85]. Nevertheless, US fails to identify stones in > 40% of children [86-89] and provides limited information on renal function.

Plain films (KUB radiography)
Kidney-ureter-bladder radiography can help to identify stones and their radiopacity, and facilitate follow-up.

Intravenous urography (IVU)
The radiation dose for IVU is comparable to that for voiding cystourethrography (0.33 mSV) [90]. However, the need for contrast medium injection is a major drawback.

Helical computed tomography (CT)
Recent low-dose CT protocols have been shown to significantly reduce radiation exposure [48,91]. In children, only 5% of stones escape detection by NCCT [84,91,92]. Sedation or anaesthesia is rarely needed with modern high-speed CT equipment.

Magnetic resonance urography (MRU)
Magnetic resonance urography cannot be used to detect urinary stones. However, it might provide detailed anatomical information about the urinary collecting system, the location of an obstruction or stenosis in the ureter, and renal parenchymal morphology [93].

3.3.3.2.1.Summary of evidence and guidelines for diagnostic imaging in children

Summary of evidence	LE
Ultrasound is the first-line imaging modality in children when a stone is suspected; it should include the kidney, fluid-filled bladder and the ureter next to the kidney and the (filled) bladder.	2b
A kidney-ureter-bladder radiography (or low-dose NCCT) is an alternative investigation if US will not provide the required information.	2b

Recommendations	Strength rating
In all children, complete a metabolic evaluation based on stone analysis.	Strong
Collect stone material for analysis to classify the stone type.	Strong
Perform ultrasound as first-line imaging modality in children when a stone is suspected; it should include the kidney, fluid-filled bladder and the ureter.	Strong
Perform a kidney-ureter-bladder radiography (or low-dose non-contrast-enhanced computed tomography) if ultrasound will not provide the required information.	Strong

3.4.Disease Management

3.4.1.Renal colic

Pain relief
Non-steroidal anti-inflammatory drugs (NSAIDs) (including metamizoledipyrone), and paracetamol are effective in patients with acute stone colic [94-96], and have better analgesic efficacy than opioids [97]. The addition of antispasmodics to NSAIDs does not result in better pain control. Data on other types of non-opioid, non-NSAID medication is scarce [98]. Patients receiving NSAIDs are less likely to require further analgesia in the short term. It should be taken into consideration that the use of diclofenac and ibuprofen increased major coronary events [99,100]. Diclofenac is contraindicated in patients with congestive heart failure (New York Heart Association class II-IV), ischaemic heart disease and peripheral arterial- and cerebrovascular disease. Patients with significant risk factors for cardiovascular events should be treated with diclofenac only after careful consideration. As risks increase with dose and duration, the lowest effective dose should be used for the shortest duration [99,100].

Opioids, particularly pethidine, are associated with a high rate of vomiting compared to NSAIDs, and carry a greater likelihood of further analgesia being needed [96,101] (see below). If an opioid is used, it is recommended that it is not pethidine.

Prevention of recurrent renal colic
>Facilitation of passage of ureteral stones is discussed in Section 3.4.9.

For patients with ureteral stones that are expected to pass spontaneously, NSAID tablets or suppositories (e.g., diclofenac sodium, 100-150 mg/day, 3-10 days) may help reduce inflammation and the risk of recurrent pain [102,103]. Although diclofenac can affect renal function in patients with already reduced function, it has no functional effect in patients with normal renal function [104].

The SR and MA by Hollingsworth et al. [105] addressed pain reduction as a secondary outcome and concluded that medical expulsive therapy (MET) seems efficacious in reducing pain episodes of patients with ureteral stones.

If analgesia cannot be achieved medically, drainage, using stenting, percutaneous nephrostomy or stone removal, is indicated [106].

3.4.1.1.Summary of evidence and guidelines for the management of renal colic

Summary of evidence	LE
Non-steroidal anti-inflammatory drugs are very effective in treating renal colic and are superior to opioids.	1b
For symptomatic ureteral stones, stone removal as first-line treatment is a feasible option in selected patients.	1b

Recommendations	Strength rating
Offer a non-steroidal anti-inflammatory as the first drug of choice; e.g. metamizol*** (dipyrone); alternatively paracetamol or, depending on cardiovascular risk factors, diclofenac, indomethacin or ibuprofen*.	Strong
Offer opiates (hydromorphine, pentazocine or tramadol) as a second choice.	Weak
Offer renal decompression or ureteroscopic stone removal in case of analgesic refractory colic pain.	Strong

*Affects glomerular filtration rate (GFR) in patients with reduced renal function.

**Recommended to counteract recurrent pain after ureteral colic.

*** Maximum single oral dose recommended 1000 mg, total daily dose up to 5000 mg, not recommended in
the last three months of pregnancy. For more information see: European Medicines Agency. EMA/853069/2018. 14 December 2018.

3.4.2.Management of sepsis and/or anuria in obstructed kidney

The obstructed kidney with all signs of urinary tract infection (UTI) and/or anuria is a urological emergency. Urgent decompression is often necessary to prevent further complications in infected hydronephrosis secondary to stone-induced, unilateral or bilateral, renal obstruction.

Decompression
Currently, there are two options for urgent decompression of obstructed collecting systems:

placement of an indwelling ureteral stent;
percutaneous placement of a nephrostomy tube.

There is little evidence to support the superiority of percutaneous nephrostomy over retrograde stenting for primary treatment of infected hydronephrosis. There is no good quality evidence to suggest that ureteral stenting has more complications than percutaneous nephrostomy [107,108].

Only one RCT [109] compared different modalities of decompression of acute infected hydronephrosis. The complications of percutaneous nephrostomy insertion have been reported consistently, but those of ureteral stent insertion are less well described [107]. Definitive stone removal should be delayed until the infection is cleared following a complete course of antimicrobial therapy. A small RCT showed the feasibility of immediate ureteroscopic stone removal combined with appropriate antibiotic regimen; however, at the cost of longer hospital stay and higher analgesic requirements [110].

Further measures
Following urgent decompression of the obstructed and infected urinary collecting system, both urine- and blood samples should be sent for culture-antibiogram sensitivity testing and antibiotics should be initiated immediately thereafter or continued, if initiated prior to testing. The regimen should be re-evaluated in the light of the culture-antibiogram test. Although clinically well accepted, the impact of a second antibiogram test on treatment outcome has not yet been evaluated. Intensive care might become necessary [111].

3.4.2.1.Summary of evidence and guidelines for the management of sepsis and anuria

Summary of evidence	LE
For decompression of the renal collecting system, ureteral stents and percutaneous nephrostomy catheters are equally effective.	1b

Recommendations	Strength rating
Urgently decompress the collecting system in case of sepsis with obstructing stones, using percutaneous drainage or ureteral stenting.	Strong
Delay definitive treatment of the stone until sepsis is resolved.	Strong
Collect (again) urine for antibiogram test following decompression.	Strong
Start antibiotics immediately (+ intensive care, if necessary).	Strong
Re-evaluate antibiotic regimen following antibiogram findings.	Strong

3.4.3.Medical expulsive therapy

Medical expulsive therapy should only be used in informed patients if active stone removal is not indicated. Treatment should be discontinued if complications develop (infection, refractory pain, deterioration of renal function). Several drug classes are used for MET [112-115]. When using α-blockers for MET, possible side effects include retrograde ejaculation and hypotension [103].

Patients treated with α-blockers, calcium-channel inhibitors (nifedipine) and phosphodiesterase type 5 (PDE-5) inhibitors (tadalafil) are more likely to pass stones with fewer colic episodes than those not receiving such therapy [103,116,117]. Based on studies with a limited number of patients [115,117-119], no recommendation for the use of PDE-5 Inhibitors or corticosteroids in combination with α-blockers in MET can be made.

Tamsulosin showed an overall superiority to nifedipine for distal ureteral calculi [120]. A class effect of α-blockers has been demonstrated in MAs [119,121]. However, there is contradictory evidence between these studies and several well-designed, multicentre, placebo-controlled, double-blinded randomised studies showing limited, or no, benefit using α-blockers, besides some advantage for distal ureteral stones > 5 mm) [122-124]. A published MA, including 55 trials with a data search cut-off of July 1st 2015, also including the publications addressed above, assessed stone passage as primary outcome [105]. Based on the well-designed sensitivity analyses of this MA, α-blockers promote spontaneous stone expulsion of large stones located in any part of the ureter. There are small trials of uncertain quality suggesting tadalafil alone or in combination with tamsulosin may be beneficial for ureteric stone passage [117].

The primary outcome of most trials assessing MET was stone passage, or follow up, up to four weeks. No data are currently available to support other time-intervals.

The Panel concludes that MET seems efficacious in the treatment of patients with ureteral stones who are amenable to conservative management. The greatest benefit might be among those with > 5 mm distal stones [125].

3.4.3.1.Summary of evidence and guideline for MET

Summary of evidence	LE
Medical explusive therapy seems to be efficacious treating patients with ureteral stones who are amenable to conservative management. The greatest benefit might be among those with > 5 mm (distal) stones.	1a
Insufficient data exist to support the use of PDE-5 Inhibitors or corticosteroids in combination with α-blockers as an accelerating adjunct.	2a
α-blockers increase stone expulsion rates in distal ureteral stones > 5 mm.	1a
A class effect of α-blockers has been demonstrated.	1a

Recommendation	Strength rating
Offer α-blockers as medical expulsive therapy as one of the treatment options for (distal) ureteral stones > 5 mm.	Strong

Medical expulsive therapy in special situations is addressed in the relevant chapters.

3.4.4.Chemolysis

Percutaneous irrigation chemolysis
Percutaneous chemolysis is rarely used nowadays, for practical reasons. Percutaneous irrigation chemolysis may be an option for infection- and theoretically also for uric acid stones. For dissolution of struvite stones, Suby’s G solution (10% hemiacidrin; pH 3.5-4) can be used. The method has been described in case series along with literature reviews [126-128].

Oral chemolysis
Stones composed of uric acid, but not sodium or ammonium urate stones, can be dissolved by oral chemolysis. Prior stone analysis may provide information on stone composition. Urinary pH measurement and X-ray characteristics can provide information on the type of stone.

Oral chemolitholysis is based on alkalinisation of urine by application of alkaline citrate or sodium bicarbonate. The pH should be adjusted to 7.0-7.2. Chemolysis is more effective at a higher pH, which might, however, promote calcium phosphate stone formation. Patients will need to adjust the dosage of alkalising medication by self-monitoring the pH of their urine. No RCTs are available for this therapy, which has been in use for decades. Rodman, et al. [129] reviewed the principles and provided guidance to its clinical use, which was supported by Becker, et al. in 2007 [130]. Monitoring of radiolucent stones during therapy is the domain of US; however, repeat-NCCT might be necessary [129,130].

In the case of uric acid obstruction of the collecting system, oral chemolysis in combination with urinary drainage is indicated [131]. A combination of alkalinisation with tamsulosin can increase the frequency of spontaneous passage of distal ureteral uric acid stones as shown in one RCT for stones > 5 mm [131].

3.4.4.1.Summary of evidence and guidelines for chemolysis

Summary of evidence	LE
Irrigation chemolysis has been in limited clinical use to dissolve struvite stones.	3
Uric acid stones can be dissolved based on oral alkalinisation of the urine above 7.0.	3
For obstructing uric acid stones, a combination of oral chemolysis with tamsulosin is more effective than each substance alone, particularly in stones > 8 mm.	1b

Recommendations (oral chemolysis of uric acid stones)	Strength rating
Inform the patient how to monitor urine-pH by dipstick and to modify the dosage of alkalising medication according to urine pH, as changes in urine pH are a direct consequence of such medication.	Strong
Carefully monitor patients during/after oral chemolysis of uric acid stones.	Strong
Combine oral chemolysis with tamsulosin in case of (larger) ureteral stones (if active intervention is not indicated).	Weak

3.4.5.Extracorporeal shock wave lithotripsy (SWL)

The success of SWL depends on the efficacy of the lithotripter and the following factors:

size, location (ureteral, pelvic or calyceal), and composition (hardness) of the stones (Section 3.4.9.3);
patient’s habitus (Section 3.4.10.3);
performance of SWL (best practice, see below).

Each of these factors significantly influences the retreatment rate and final outcome of SWL.

Best clinical practice

Stenting

Routine use of internal stents before SWL does not improve stone free rates (SFRs), nor lowers the number of auxiliary treatments. It may, however, reduce formation of steinstrasse [132-135].

Pacemaker

Patients with a pacemaker can be treated with SWL, provided that appropriate technical precautions are taken. Patients with implanted cardioverter defibrillators must be managed with special care (firing mode temporarily reprogrammed during SWL treatment). However, this might not be necessary with new-generation lithotripters [136].

Shock wave rate

Lowering shock wave frequency from 120 to 60-90 shock waves/min improves SFRs [137-142]. Tissue damage increases with shock wave frequency [143-148].

Number of shock waves, energy setting and repeat treatment sessions

The number of shock waves that can be delivered at each session depends on the type of lithotripter and shock wave power. There is no consensus on the maximum number of shock waves [149].

Starting SWL on a lower energy setting with stepwise power (and SWL sequence) ramping can achieve vasoconstriction during treatment [145], which prevents renal injury [150-152]. Animal studies [153] and a prospective randomised study [154] have shown better SFRs (96% vs. 72%) using stepwise power ramping, but no difference has been found for fragmentation or evidence of complications after SWL, irrespective of whether ramping was used [155].

There are no conclusive data on the intervals required between repeated SWL sessions. However, clinical experience indicates that repeat sessions are feasible (within 1 day for ureteral stones).

Improvement of acoustic coupling

Proper acoustic coupling between the cushion of the treatment head and the patient’s skin is important. Defects (air pockets) in the coupling gel deflect 99% of shock waves [156]. Ultrasound gel is probably the most widely used agent available for use as a lithotripsy coupling agent [157].

Procedural control

Results of treatment are operator dependent, and experienced clinicians obtain better results. During the procedure, careful imaging control of localisation contributes to outcome quality [158].

Pain control

Careful control of pain during treatment is necessary to limit pain-induced movements and excessive respiratory excursions [159-162].

Antibiotic prophylaxis

No standard antibiotic prophylaxis before SWL is recommended. However, prophylaxis is recommended in the case of internal stent placement ahead of anticipated treatments and in the presence of increased bacterial burden (e.g., indwelling catheter, nephrostomy tube, or infectious stones) [64,163,164].

Medical therapy after extracorporeal shock wave lithotripsy

In spite of conflicting results, most RCTs and several MAs support MET after SWL for ureteral or renal stones as adjunct to expedite expulsion and to increase SFRs. Medical expulsion therapy might also reduce analgesic requirements [165-172].

Complications of extracorporeal shock wave lithotripsy

Compared to PNL and ureteroscopy (URS), there are fewer overall complications with SWL [173,174] (Table 3.5).

Table 3.5: Shock wave lithotripsy-related complications [175-189]

Complications			%	Reference
Related to stone fragments	Steinstrasse		4 - 7	[187-189]
	Regrowth of residual fragments		21 - 59	[176,177]
	Renal colic		2 - 4	[178]
Infectious	Bacteriuria in non-infection stones		7.7 - 23	[176,179]
Infectious	Sepsis		1 – 2.7	[176,179]
Tissue effect	Renal	Haematoma, symptomatic	< 1	[180]
	Renal	Haematoma, asymptomatic	4 – 19	[180]
	Cardiovascular	Dysrhythmia	11 – 59	[176,181]
	Cardiovascular	Morbid cardiac events	Case reports	[176,181]
	Gastrointestinal	Bowel perforation	Case reports	[182-184]
	Gastrointestinal	Liver, spleen haematoma	Case reports	[175,184-186]

The relationship between SWL and hypertension or diabetes is unclear. Published data are contradictory; however, no evidence exists supporting the hypothesis that SWL may cause long-term adverse effects [190-195].

3.4.5.1.Summary of evidence and guidelines for SWL

Summary of evidence	LE
Stepwise power ramping prevents renal injury.	1b
Clinical experience has shown that repeat sessions are feasible (within one day for ureteral stones).	4
Optimal shock wave frequency is 1.0 to 1.5 Hz.	1a
Proper acoustic coupling between the cushion of the treatment head and the patient’s skin is important.	2
Careful imaging control of localisation of stone contributes to outcome of treatment.	2a
Careful control of pain during treatment is necessary to limit pain-induced movements and excessive respiratory excursions.	1a
Antibiotic prophylaxis is recommended in the case of internal stent placement, infected stones or bacteriuria.	1a

Recommendations	Strength rating
Ensure correct use of the coupling agent because this is crucial for effective shock wave transportation.	Strong
Maintain careful fluoroscopic and/or ultrasonographic monitoring during shock wave lithotripsy (SWL).	Strong
Use proper analgesia because it improves treatment results by limiting pain-induced movements and excessive respiratory excursions.	Strong
In the case of infected stones or bacteriuria, prescribe antibiotics prior to SWL.	Strong

3.4.6.Ureteroscopy (URS) (retrograde and antegrade, RIRS)

The current standard for rigid ureterorenoscopes is tip diameters of < 8 F. Rigid URS can be used for the whole ureter [190]. However, technical improvements, as well as the availability of digital scopes, also favour the use of flexible ureteroscopes in the ureter [196].

Percutaneous antegrade removal of ureteral stones is a consideration in selected cases, i.e. large (> 15mm), impacted proximal ureteral calculi in a dilated renal collecting system [197-199], or when the ureter is not amenable to retrograde manipulation [200-204].

Ureteroscopy for renal stones (RIRS)

Technical improvements including endoscope miniaturisation, improved deflection mechanism, enhanced optical quality and tools, and introduction of disposables have led to an increased use of URS for both renal and ureteral stones. Major technological progress has been achieved for RIRS. A recent SR addressing renal stones > 2 cm showed a cumulative SFR of 91% with 1.45 procedures/patient; 4.5% of the complications were > Clavien 3 [196,205,206]. Digital scopes demonstrate shorter operation times due to the improvement in image quality [205].

Stones that cannot be extracted directly must be disintegrated. If it is difficult to access stones within the lower renal pole that need disintegration; it may help to displace them into a more accessible calyx [207].

Best clinical practice in ureteroscopy

Access to the upper urinary tract

Most interventions are performed under general anaesthesia, although local or spinal anaesthesia is possible. Intravenous sedation is suitable for female patients with distal ureteral stones [208].

Antegrade URS is an option for large, impacted, proximal ureteral calculi [197-200].

Safety aspects

Fluoroscopic equipment must be available in the odds ratio (OR). We recommend placement of a safety wire, even though some groups have demonstrated that URS can be performed without it [209-211]. Balloon and plastic dilators should be available, if necessary.

Prior rigid URS can be helpful for optical dilatation followed by flexible URS, if necessary. If ureteral access is not possible, insertion of a JJ stent followed by URS after seven to fourteen days offers an alternative [212]. Bilateral URS during the same session is feasible resulting in equivalent-to-lower SFRs, but slightly higher overall complication rates (mostly minor, Clavien I and II) [213,214].

Ureteral access sheaths

Hydrophilic-coated ureteral access sheaths, which are available in different calibres (inner diameter from 9 French (F) upwards), can be inserted via a guide wire, with the tip placed in the proximal ureter.

Ureteral access sheaths allow easy, multiple, access to the UUT and therefore significantly facilitate URS. The use of ureteral access sheaths improves vision by establishing a continuous outflow, decrease intrarenal pressure, and potentially reduce operating time [215,216].

The insertion of ureteral access sheaths may lead to ureteral damage, whereas the risk is lowest in pre-stented systems [217]. No data on long-term side effects are available [217,218]. Whilst larger cohort series showed no difference in SFRs and ureteral damage, they did show lower post-operative infectious complications [219].

Use of ureteral access sheaths depends on the surgeon’s preference.

Stone extraction

The aim of URS is complete stone removal. “Dust and go” strategies should be limited to the treatment of large (renal) stones [220]. Stones can be extracted by endoscopic forceps or baskets. Only baskets made of nitinol can be used for flexible URS [221].

Intracorporeal lithotripsy

The most effective lithotripsy system is the holmium:yttrium-aluminium-garnet (Ho:YAG) laser, which is currently the optimum standard for URS and flexible nephroscopy (Section 3.4.6), because it is effective in all stone types [222,223]. Pneumatic and US systems can be used with high disintegration efficacy in rigid URS [224,225].

However, stone migration into the kidney is a common problem, which can be prevented by placement of special anti-migration tools proximal of the stone [226]. Medical expulsion therapy following Ho:YAG laser lithotripsy increases SFRs and reduces colic episodes [227].

Stenting before and after URS

Routine stenting is not necessary before URS. However, pre-stenting facilitates ureteroscopic management of stones, improves the SFR, and reduces intra-operative complications [228,229].

Randomised prospective trials have found that routine stenting after uncomplicated URS (complete stone removal) is not necessary; stenting might be associated with higher post-operative morbidity and costs [230-233]. A ureteral catheter with a shorter indwelling time (one day) may also be used, with similar results [234].

Stents should be inserted in patients who are at increased risk of complications (e.g., ureteral trauma, residual fragments, bleeding, perforation, UTIs, or pregnancy), and in all doubtful cases, to avoid stressful emergencies. The ideal duration of stenting is not known. Most urologists favour 1-2 weeks after URS. Alpha-blockers reduce the morbidity of ureteral stents and increase tolerability [235,236].

Medical expulsive therapy after ureteroscopy

Medical expulsion therapy following Ho:YAG laser lithotripsy accelerates the spontaneous passage of fragments and reduces episodes of colic [227].

Complications of ureteroscopy

The overall complication rate after URS is 9-25% [190,237,238]. Most complications are minor and do not require intervention. Ureteral avulsion and strictures are rare (< 1%). Previous perforations are the most important risk factor for complications.

3.4.6.1.Summary of evidence and guidelines for retrograde URS, RIRS and antegrade ureteroscopy

Summary of evidence	LE
In uncomplicated URS, a stent need not be inserted.	1a
In URS (in particular for renal stones), pre-stenting has been shown to improve outcome.	1b
An α-blocker can reduce stent-related symptoms and colic episodes.	1a
Medical expulsion therapy following Ho:YAG laser lithotripsy accelerates the spontaneous passage of fragments and reduces episodes of colic.	1b
The most effective lithotripsy system for flexible ureteroscopy is the Ho:YAG laser.	2a
Pneumatic and US systems can be used with high disintegration efficacy in rigid URS.	2a
Medical expulsion therapy following Ho:YAG laser lithotripsy increases SFRs and reduces colic episodes.	1b
Percutaneous antegrade removal of proximal ureter stones or laparoscopic ureterolithotomy are feasible alternatives to retrograde ureteroscopy, in selected cases.	1a

Recommendations	Strength rating
Use holmium: yttrium-aluminium-garnet (Ho:YAG) laser lithotripsy for (flexible) ureteroscopy (URS).	Strong
Perform stone extraction only under direct endoscopic visualisation of the stone.	Strong
Do not insert a stent in uncomplicated cases.	Strong
Pre-stenting facilitates URS and improves outcomes of URS (in particular for renal stones).	Strong
Offer medical expulsive therapy for patients suffering from stent-related symptoms and after Ho:YAG laser lithotripsy to facilitate the passage of fragments.	Strong
Use percutaneous antegrade removal of ureteral stones as an alternative when shock wave lithotripsy (SWL) is not indicated or has failed, and when the upper urinary tract is not amenable to retrograde URS.	Strong
Use flexible URS in case percutaneous nephrolithotomy or SWL are not an option (even for stones > 2 cm). However, in that case there is a higher risk that a follow-up procedure and placement of a ureteral stent may be needed.	Strong

3.4.7.Percutaneous nephrolithotomy

Percutaneous nephrolithotripsy remains the standard procedure for large renal calculi. Different rigid and flexible endoscopes are available and the selection is mainly based on the surgeon’s own preference. Standard access tracts are 24-30 F. Smaller access sheaths, < 18 F, were initially introduced for paediatric use, but are now increasingly utilised in the adult population [239].

Contraindications

Patients receiving anti-coagulant therapy must be monitored carefully pre- and post-operatively. Anti-coagulant therapy must be discontinued before PNL [240].

Other important contraindications include:

untreated UTI;
tumour in the presumptive access tract area;
potential malignant kidney tumour;
pregnancy (Section 3.4.14.1).

Best clinical practice

Intracorporeal lithotripsy

Several methods for intracorporeal lithotripsy during PNL are available. Ultrasonic and pneumatic systems are most commonly used for rigid nephroscopy, whilst laser is increasingly used for miniaturised instruments [241]. Flexible endoscopes also require laser lithotripsy to maintain tip deflection, with the Ho:YAG laser having become the standard.

Pre-operative imaging

Pre-procedural imaging evaluations are summarised in Section 3.3.1. In particular, US or CT of the kidney and the surrounding structures can provide information regarding interpositioned organs within the planned percutaneous path (e.g., spleen, liver, large bowel, pleura, and lung) [242].

Positioning of the patient

Both prone and supine positions are equally safe, although the supine position confers some advantages, it depends on appropriate equipment being available to position the patient correctly, for example, X-ray devices and an operating table. Most studies cannot demonstrate an advantage of supine PNL in terms of OR time. Prone position offers more options for puncture and is therefore preferred for upper pole or multiple accesses [243-245]. On the other hand, supine position allows simultaneous retrograde access to the collecting system, using flexible ureteroscope [246].

Puncture

Although fluoroscopy is the most common intra-operative imaging method, the (additional) use of US reduces radiation exposure [242,247].

Pre-operative CT or intra-operative US allows identification of the tissue between the skin and kidney and lowers the incidence of visceral injury. The calyceal puncture may be done under direct visualisation using simultaneous flexible URS [247-251].

Dilatation

Dilatation of the percutaneous access tract can be achieved using a metallic telescope, single (serial) dilators, or a balloon dilatator. Although there are papers demonstrating that single step dilation is equally effective as other methods, the difference in outcomes is most likely related to surgeon experience rather than to the technology used.

Choice of instruments

The Urolithiasis Panel performed a SR assessing the outcomes of PNL using smaller tract sizes (< 22 F, mini-PNL) for removing renal calculi [239]. Stone-free rates were comparable in miniaturised and standard PNL procedures. Procedures performed with small instruments tend to be associated with significantly lower blood loss, but the duration of procedure tend to be significantly longer. There were no significant differences in any other complications. However, the quality of the evidence was poor with only two RCTs and the majority of the remaining studies were single-arm case series only. Furthermore, the tract sizes used, and types of stones treated, were heterogeneous; therefore, the risk of bias and confounding were high.

Nephrostomy and stents

The decision on whether, or not, to place a nephrostomy tube at the conclusion of the PNL procedure depends on several factors, including:

presence of residual stones;
likelihood of a second-look procedure;
significant intra-operative blood loss;
urine extravasation;
ureteral obstruction;
potential persistent bacteriuria due to infected stones;
solitary kidney;
bleeding diathesis;
planned percutaneous chemolitholysis.

Small-bore nephrostomies seem to have advantages in terms of post-operative pain [252-254]. Tubeless PNL is performed without a nephrostomy tube. When neither a nephrostomy tube nor a ureteral stent is introduced, the procedure is known as totally tubeless PNL [255]. In uncomplicated cases, the latter procedure results in a shorter hospital stay, with no disadvantages reported [256-258].

Complications of percutaneous nephrolithotomy

A systematic review of almost 12,000 patients shows the incidence of complications associated with PNL; fever 10.8%, transfusion 7%, thoracic complication 1.5%, sepsis 0.5%, organ injury 0.4%, embolisation 0.4%, urinoma 0.2%, and death 0.05% [259].

Peri-operative fever can occur, even with a sterile pre-operative urinary culture and peri-operative antibiotic prophylaxis, because the renal stones themselves may be a source of infection. Intra-operative renal stone culture may therefore help to select post-operative antibiotics [260,261]. Intra-operative irrigation pressure < 30 mmHg and unobstructed post-operative urinary drainage may be important factors in preventing post-operative sepsis [262]. Bleeding after PNL may be treated by briefly clamping of the nephrostomy tube. Superselective embolic occlusion of the arterial branch may become necessary in the case of severe bleeding.

3.4.7.1.Summary of evidence and guidelines for endourology techniques for renal stone removal

Summary of evidence	LE
Imaging of the kidney with US or CT can provide information regarding interpositioned organs within the planned percutaneous path (e.g., spleen, liver, large bowel, pleura, and lung).	1a
Both prone and supine positions are equally safe, but neither has a proven advantage in operating time or SFR.	1a
Percutaneous nephrolithotomy performed with small instruments tends to be associated with significantly lower blood loss, but the duration of procedure tended to be significantly longer. There are no significant differences in SFR or any other complications.	1a
In uncomplicated cases, a totally tubeless PNL results in a shorter hospital stay, with no increase in complication rate.	1a

Recommendations	Strength rating
Perform pre-procedural imaging, including contrast medium where possible or retrograde study when starting the procedure, to assess stone comprehensiveness and anatomy of the collecting system to ensure safe access to the renal stone.	Strong
In uncomplicated cases, perform a tubeless (without nephrostomy tube) or totally tubeless (without nephrostomy tube and ureteral stent) percutaneous nephrolithotomy procedure.	Strong

3.4.8.General recommendations and precautions for stone removal

3.4.8.1.Antibiotic therapy

Urinary tract infections should always be treated if stone removal is planned. In patients with clinically significant infection and obstruction, drainage should be performed for several days before starting stone removal. A urine culture or urinary microscopy should be performed before treatment [263].

Perioperative antibiotic prophylaxis

For prevention of infection following URS and percutaneous stone removal, no clear-cut evidence exists [264]. In a review of a large database of patients undergoing PNL, it was found that in patients with negative baseline urine culture, antibiotic prophylaxis significantly reduced the rate of post-operative fever and other complications [265]. Single dose administration was found to be sufficient [266].

Recommendations	Strength rating
Obtain a urine culture or perform urinary microscopy before any treatment is planned.	Strong
Exclude or treat urinary tract infections prior to stone removal.	Strong
Offer peri-operative antibiotic prophylaxis to all patients undergoing endourological treatment.	Strong

3.4.8.2.Antithrombotic therapy and stone treatment

Patients with a bleeding diathesis, or receiving antithrombotic therapy, should be referred to an internist for appropriate therapeutic measures before deciding on stone management [267-271]. In patients with an uncorrected bleeding diathesis, the following are at elevated risk of haemorrhage or perinephric haematoma (PNH) (high-risk procedures):

SWL (hazard ratio of PNH up to 4.2 during anti-coagulant/anti-platelet medication [272]);
PNL;
percutaneous nephrostomy;
laroscopic surgery;
open surgery [267,273,274].

Shock wave lithotripsy is feasible and safe after correction of the underlying coagulopathy [275-279]. In the case of an uncorrected bleeding disorder or continued antithrombotic therapy, URS, in contrast to SWL and PNL, might offer an alternative approach since it is associated with less morbidity [280-282]. Despite appropriate cessation of anti-platelet agents, following standardised protocols, prolonged haematuria in tube drainage after PNL has been reported [283]. Only data on flexible URS are available which support the superiority of URS in the treatment of proximal ureteral stones [284,285].

Table 3.6: Risk stratification for bleeding [269-271,286]

Low-risk bleeding procedures

Cystoscopy

Flexible cystoscopy

Ureteral catheterisation

Extraction of ureteral stent

Ureteroscopy

High-risk bleeding procedures

Shock wave lithotripsy

Percutaneous nephrostomy

Percutaneous nephrolithotripsy

Table 3.7: Suggested strategy for antithrombotic therapy in stone removal [269-271]

(In collaboration with a cardiologist/internist weigh the risks and benefits of discontinuation of therapy, vs. delaying elective surgical procedures).

	Bleeding risk of planned procedure	Risk of thromboembolism
	Bleeding risk of planned procedure	Low risk	Intermediate risk	High risk
Warfarin Dabigatran Rivaroxaban Apixaban	Low-risk procedure	May be continued	Bridging therapy	Bridging therapy
Warfarin Dabigatran Rivaroxaban Apixaban	High-risk procedure	May be temporarily discontinued at appropriate interval. Bridging therapy is strongly recommended.	Bridging therapy	Bridging therapy
Aspirin	Low-risk procedure	Continue	Continue	Elective surgery: postpone. Non deferrable surgery: continue
Aspirin	High-risk procedure	Discontinue	Elective surgery: postpone. Non-deferrable surgery: continue, if is possible.	Elective surgery: postpone. Non-deferrable surgery: continue.
Thienopyridine agents (P2Y12 receptor inhibitors)	Low-risk procedure	Discontinue five days before intervention. Resume within 24-72 hours with a loading dose.	Continue	Elective surgery: postpone. Non-deferrable surgery: continue.
Thienopyridine agents (P2Y12 receptor inhibitors)	High-risk procedure	Discontinue five days before intervention and resume within 24-72 hours with a loading dose.	Elective surgery: postpone. Non-deferrable surgery: discontinue five days before procedure and resume within 24-72 hours with a loading dose. Bridging therapy -glycoprotein IIb/IIIa inhibitors if aspirin is discontinued.	Elective surgery: postpone. Non-deferrable surgery: discontinue five days before procedure and resume within 24-72 hours, with a loading dose. Bridging therapy -glycoprotein IIb/IIIa inhibitors.

3.4.8.2.1.Summary of evidence and guidelines for antithrombotic therapy and stone treatment

Summary of evidence	LE
Active surveillance is indicated in patients at high risk for thrombotic complications in the presence of an asymptomatic calyceal stone.	4
The temporary discontinuation, or bridging of antithrombotic therapy in high-risk patients, should be discussed with the internist.	3
Retrograde (flexible) URS stone removal is associated with less morbidity in patients when antithrombotic therapy cannot be discontinued.	2a

Recommendations	Strength rating
Offer active surveillance to patients at high risk of thrombotic complications in the presence of an asymptomatic calyceal stone.	Weak
Decide on temporary discontinuation, or bridging of antithrombotic therapy in high-risk patients, in consultation with the internist.	Strong
Retrograde (flexible) URS is the preferred intervention if stone removal is essential and antithrombotic therapy cannot be discontinued, since it is associated with less morbidity.	Strong

3.4.8.3.Obesity

A high BMI can pose a higher anaesthetic risk, and a lower success rate after SWL [287].

3.4.8.4.Stone composition

Stones composed of brushite, calcium oxalate monohydrate, or cystine are particularly hard, as well as homogeneous stones with a high density on NCCT [42,288]. Percutaneous nephrolithotomy or RIRS and URS are alternatives for removal of large SWL-resistant stones.

3.4.8.4.1.Guidelines for stone composition

Recommendations	Strength rating
Consider the stone composition before deciding on the method of removal, based on patient history, former stone analysis of the patient or Hounsfield unit on unenhanced computed tomography.	Strong
Attempt to dissolve radiolucent stones (see section 3.4.4.)	Strong

3.4.8.5.Contraindications of procedures

Contraindications of extracorporeal SWL

There are several contraindications to the use of extracorporeal SWL, including:

pregnancy, due to the potential effects on the foetus [289];
bleeding diatheses, which should be compensated for at least 24 hours before and 48 hours after treatment [290];
uncontrolled UTIs;
severe skeletal malformations and severe obesity, which prevent targeting of the stone;
arterial aneurysm in the vicinity of the stone [291];
anatomical obstruction distal to the stone.

Contraindications of URS

Apart from general problems, for example with general anaesthesia or untreated UTIs, URS can be performed in all patients without any specific contraindications.

Contraindications of PNL

Patients receiving anti-coagulant therapy must be monitored carefully pre- and post-operatively. Anti-coagulant therapy must be discontinued before PNL [282]. Other important contraindications include:

untreated UTI;
tumour in the presumptive access tract area;
potential malignant kidney tumour;
pregnancy (Section 3.4.14.1).

3.4.9.Specific stone management of ureteral stones

3.4.9.1.Conservative treatment/observation

There are only limited data regarding spontaneous stone passage according to stone size [292]. It is estimated that 95% of stones up to 4 mm pass within 40 days [190].

Based on an analysis of available evidence, an exact cut-off size for stones that are likely to pass spontaneously cannot be provided; < 10 mm may be considered a best estimate [190]. Therefore, the Panel decided not to include stone size but rather recommend “small”, suggesting < 6 mm. The Panel is aware of the fact that spontaneous stone expulsion decreases with increasing stone size and that there are differences between individual patients.

3.4.9.2.Pharmacological treatment, medical explusive therapy

Medical expulsive therapy should only be used in informed patients if active stone removal is not indicated. Treatment should be discontinued if complications develop (infection, refractory pain, deterioration of renal function). In case of known uric acid stones in the distal ureter, a combination of alkalinisation with tamsulosin can increase the frequency of spontaneous passage. For details see Sections 3.4.3 and 3.4.4.

3.4.9.3.Indications for active removal of ureteral stones

Indications for active removal of ureteral stones are [190,292,293]:

stones with a low likelihood of spontaneous passage;
persistent pain despite adequate analgesic medication;
persistent obstruction;
renal insufficiency (renal failure, bilateral obstruction, or single kidney).

For general recommendations and precautions see Section 3.4.8

3.4.9.4.Selection of procedure for active removal of ureteral stones

Overall SFRs after URS or SWL for ureteral stones are comparable. However, larger stones achieve earlier stone-free status with URS. Although URS is effective for ureteral calculi, it has greater potential for complications. However, in the current endourological era, the complication rate and morbidity of URS have been significantly reduced [294]. It has been demonstrated that URS is a safe option in obese patients (BMI > 30 kg/m2) with comparable SFRs and complication rates. However, in morbidly obese patients (BMI > 35 kg/m2) the overall complication rates double [295].

The Panel performed an SR to assess the benefits and harms of URS compared to SWL [296]. Compared with SWL, URS was associated with a significantly greater SFR up to four weeks, but the difference was not significant at three months in the included studies. Ureteroscopy was associated with fewer retreatments and need for secondary procedures, but with a higher need for adjunctive procedures, greater complication rates and longer hospital stay. Counterbalancing for URS’s higher SFRs, SWL is associated with least morbidity. Clavien-Dindo grade complications were, if reported, less frequent in patients treated with SWL.

Obesity can cause a lower success rate after SWL and PNL and may influence the choice of treatment.

Bleeding disorder

Ureteroscopy can be performed in patients with bleeding disorders, with a moderate increase in complications (see also Section 3.4.8.2) [282].

3.4.9.4.1.Summary of evidence and guidelines for selection of procedure for active removal of ureteral stones

Summary of evidence	LE
Observation is feasible in informed patients who develop no complications (infection, refractory pain, deterioration of renal function).	1a
Medical expulsive therapy seems to be efficacious treating patients with ureteral stones who are amenable to conservative management. The greatest benefit might be among those with > 5 mm (distal) stones.	1a
Compared with SWL, URS was associated with significantly greater SFRs up to four weeks, but the difference was not significant at three months in the included studies.	1a
Ureteroscopy was associated with fewer retreatments and need for secondary procedures, but with a higher need for adjunctive procedures, greater complication rates and longer hospital stay.	1a
In the case of severe obesity, URS is a more promising therapeutic option than SWL.	2b

Recommendations	Strength rating
In patients with newly diagnosed small* ureteral stones, if active removal is not indicated (Section 3.4.9.3), observe patient initially with periodic evaluation.	Strong
Offer α-blockers as medical expulsive therapy as one of the treatment options for (distal) ureteral stones > 5 mm.	Strong
Inform patients that ureteroscopy (URS) has a better chance of achieving stone-free status with a single procedure.	Strong
Inform patients that URS has higher complication rates when compared to shock wave lithotripsy.	Strong
In cases of severe obesity use URS as first-line therapy for ureteral (and renal) stones.	Strong

*See stratification data [190].

Figure 3.4.1: Treatment algorithm for ureteral stones (if active stone removal is indicated)

SWL = shock wave lithotripsy; URS = Ureteroscopy.

3.4.10.Specific stone management of renal stones

The natural history of small, non-obstructing asymptomatic calculi is not well defined, and the risk of progression is unclear. There is still no consensus on the follow-up duration, timing and type of intervention. Treatment options are chemolysis or active stone removal.

3.4.10.1.Conservative treatment (observation)

Observation of renal stones, especially in calices, depends on their natural history (Section 3.4.10.3). The recommendations provided are not supported by high-level literature. There is a prospective trial supporting annual observation for asymptomatic inferior calyceal stones, < 10 mm. In case stone growth is detected, the follow-up interval should be lowered. Intervention is advised for growing stones > 5 mm [297].

3.4.10.2.Pharmacological treatment of renal stones

Dissolution of stones through pharmacological treatment is an option for uric acid stones only, but information on the composition of the stone will need to guide the type of treatment selected. See sections 3.4.4. and 3.4.8.4.

3.4.10.3.Indications for active stone removal of renal stones [298]

Indications for the removal of renal stones, include:

stone growth;
stones in high-risk patients for stone formation;
obstruction caused by stones;
infection;
symptomatic stones (e.g., pain or haematuria);
stones > 15 mm;
stones < 15 mm if observation is not the option of choice;
patient preference;
comorbidity;
social situation of the patient (e.g., profession or travelling);
choice of treatment.

The risk of a symptomatic episode or need for intervention of patients with asymptomatic renal stones seems to be ~10-25% per year, with a cumulative five-year event probability of 48.5% [297,299,300]. A prospective RCT with > 2 year clinical follow-up reported no significant difference between SWL and observation when comparing asymptomatic calyceal stones < 15 mm in terms of SFR, symptoms, requirement for additional treatment, quality of life (QoL), renal function, or hospital admission [301]. Although some have recommended prophylaxis for these stones to prevent renal colic, haematuria, infection, or stone growth, conflicting data have been reported [300,302,303]. In a follow-up period of almost five years after SWL, two series have demonstrated that up to 25% of patients with small residual fragments needed treatment [177,304]. Although the question of whether calyceal stones should be treated is still unanswered, stone growth, de novo obstruction, associated infection, and acute and/or chronic pain are indications for treatment [298,305,306].

3.4.10.4.Selection of procedure for active removal of renal stones

For general recommendations and precautions see Section 3.4.8.

3.4.10.4.1.Stones in renal pelvis or upper/middle calices

Shock wave lithotripsy, PNL and RIRS are available treatment modalities for renal calculi. While PNL efficacy is hardly affected by stone size, the SFRs after SWL or URS are inversely proportional to stone size [307-310]. Shock wave lithotripsy achieves good SFRs for stones up to 20 mm, except for those at the lower pole [309,311,312]. Endourology is considered an alternative because of the reduced need of repeated procedures and consequently a shorter time until stone-free status is achieved. Stones > 20 mm should be treated primarily by PNL, because SWL often requires multiple treatments, and is associated with an increased risk of ureteral obstruction (colic or steinstrasse) with a need for adjunctive procedures (Figure 3.4.2) [173]. Retrograde renal surgery cannot be recommended as first-line treatment for stones > 20 mm in uncomplicated cases as SFRs decrease, and staged procedures will be required [313-315]. However, it may be a first-line option in patients where PNL is not an option or contraindicated.

3.4.10.4.2.Stones in the lower renal pole

The stone clearance rate after SWL seems to be lower for stones in the inferior calyx than for other intra-renal locations. Although the disintegration efficacy of SWL is not limited compared to other locations, the fragments often remain in the calyx and cause recurrent stone formation. The reported SFR of SWL for lower pole calculi is 25-95%. The preferential use of endoscopic procedures is supported by some current reports, even for stones smaller than 1 cm [173,307,308,310,311,315-323].

The following can impair successful stone treatment by SWL [318,324-328]:

steep infundibular-pelvic angle;
long calyx;
long skin-to-stone distance;
narrow infundibulum;
Shock wave-resistant stones (calcium oxalate monohydrate, brushite, or cystine).

Further anatomical parameters cannot yet be established. Supportive measures such as inversion, vibration or hydration may facilitate stone clearance [329].

If there are negative predictors for SWL, PNL and RIRS might be reasonable alternatives, even for smaller calculi [316]. Retrograde renal surgery seems to have comparable efficacy to SWL [173,308,311,330]. Recent clinical experience has suggested a higher SFR of RIRS compared to SWL, but at the expense of greater invasiveness. Depending on operator skills, stones up to 3 cm can be treated by RIRS [206,331-333]. However, staged procedures are frequently required.

In complex stone cases, open or laparoscopic approaches are possible alternatives (see appropriate chapters).

3.4.10.5.Summary of evidence and guidelines for the management of renal stones

Summary of evidence	LE
It is still debatable whether renal stones should be treated, or whether annual follow-up is sufficient for asymptomatic calyceal stones that have remained stable for six months.	4
Although the question of whether calyceal stones should be treated is still unanswered, stone growth, de novo obstruction, associated infection, and acute and/or chronic pain are indications for treatment.	3
Percutaneous nephrolithotomy is indicated in renal stones > 2 cm as primary option.	1a

Recommendations	Strength rating
Follow-up periodically in cases where renal stones are not treated (initially after six months then yearly, evaluating symptoms and stone status [either by ultrasound, kidney-ureter bladder radiography or computed tomography]).	Strong
Offer active treatment for renal stones in case of stone growth, de novo obstruction, associated infection, and acute and/or chronic pain.	Weak
Assess comorbidity and patient preference when making treatment decisions.	Weak
Offer shock wave lithotripsy (SWL) and endourology (percutaneous nephrolithotomy [PNL], retrograde renal surgery [RIRS]) as treatment options for stones < 2 cm within the renal pelvis and upper or middle calices.	Strong
Perform PNL as first-line treatment of larger stones > 2 cm.	Strong
In case PNL is not an option, treat larger stones (> 2 cm) with flexible ureteroscopy or SWL. However, in such instances there is a higher risk that a follow-up procedure and placement of a ureteral stent may be needed.	Strong
For the lower pole, perform PNL or RIRS, even for stones > 1 cm, as the efficacy of SWL is limited (depending on favourable and unfavourable factors for SWL).	Strong

Figure 3.4.2: Treatment algorithm for renal stones (if/when active treatment is indicated)

*The term ‘Endourology’ encompasses all PNL and URS interventions.

PNL = percutaneous nephrolithotomy; RIRS = retrograde renal surgery; SWL = shock wave lithotripsy; URS = ureteroscopy.

3.4.11.Laparoscopy and open surgery

Advances in SWL and endourological surgery (URS and PNL) have significantly decreased the indications for open or laparoscopic stone surgery [334-339]. There is a consensus that most complex stones, including partial and complete staghorn stones, should be approached primarily with PNL. Additionally, a combined approach with PNL and RIRS may also be an appropriate alternative. However, if percutaneous approaches are not likely to be successful, or if multiple endourological approaches have been performed unsuccessfully; open or laparoscopic surgery may be a valid treatment option [340-346].

Few studies have reported laparoscopic stone removal. These procedures are usually reserved for special cases. When expertise is available, laparoscopic ureterolithotomy can be performed for large proximal ureteral stones as an alternative to URS or SWL [347,348]. These more invasive procedures have yielded high SFRs and lower auxiliary procedure rates [197-199,349]. A recent systematic review showed no difference in the post-operative phase for stented or unstented laparoscopic ureterolithotomy [349]. Open surgery should be considered as the last treatment option, after all other possibilities have been explored.

3.4.11.1.Summary of evidence and guideline for laparoscopy and open surgery

Recommendation	Strength rating
Offer laparoscopic or open surgical stone removal in rare cases in which shock wave lithotripsy, retrograde or antegrade ureteroscopy and percutaneous nephrolithotomy fail, or are unlikely to be successful.	Strong

3.4.12.Steinstrasse

Steinstrasse is an accumulation of stone fragments or stone gravel in the ureter and may interfere with the passage of urine [350]. Steinstrasse occurs in 4-7% cases of SWL [187], and the major factor in the development of steinstrasse formation is stone size [351].

A major problem of steinstrasse is ureteral obstruction, which may be silent in up to 23% of cases. A MA including eight RCTs (n = 876) suggests a benefit of stenting before SWL in terms of steinstrasse formation, but does not result in a benefit on SFRs or less auxiliary treatments [133].

When steinstrasse is asymptomatic, conservative treatment is an initial option. Medical expulsion therapy increases stone expulsion and reduces the need for endoscopic intervention [352,353]. In the event of UTI or fever, the urinary system should be decompressed, preferably by percutaneous nephrostomy [136,139].

3.4.12.1.Summary of evidence and guidelines for steinstrasse

Summary of evidence	LE
Medical expulsion therapy increases the stone expulsion rate of steinstrasse [352].	1b
Ureteroscopy is effective for the treatment of steinstrasse [354].	3
Only low-level evidence is available, supporting SWL or URS for the treatment of steinstrasse.	4

Recommendations	Strength rating
Treat steinstrasse associated with urinary tract infection/fever preferably with percutaneous nephrostomy.	Weak
Treat steinstrasse when large stone fragments are present with shock wave lithotripsy or ureteroscopy (in absence of signs of urinary tract infection).	Weak

3.4.13.Management of patients with residual stones

Following initial treatment with SWL, URS or PNL residual fragments may remain and require additional intervention [304,355,356]. Most of the studies indicate that initial imaging is performed on the first day or the first week after treatment. However, false positive results from dust or residual fragments that will pass spontaneously without causing any stone-related event might lead to over-treatment. As a consequence, imaging at four weeks seems most appropriate [357-359]. Compared to US, KUB and IVU, NCCT scan has a higher sensitivity to detect small residual fragments after definitive treatment of ureteral or kidney stones [360,361]. However, more than half of the patients with a residual fragment on NCCT images may not experience a stone-related event [362].

It is clear that NCCT has the highest sensitivity to detect residual fragments; however, this must be balanced against the increased detection of clinically insignificant fragments and the exposure to ionising radiation when compared with KUB and US. In the absence of high level supporting evidence, the timing of follow-up imaging studies and need for secondary intervention is left to the discretion of the treating physician.

Recurrence risk in patients with residual fragments after treatment of infection stones is higher than for other stones [363]. For all stone compositions, 21-59% of patients with residual stones required treatment within five years. Fragments > 5 mm are more likely than smaller ones to require intervention [177,364,365]. There is evidence that fragments > 2 mm are more likely to grow, although this is not associated with increased re-intervention rates at one year follow up [355].

3.4.13.1.Summary of evidence and guideline for management of patients with residual stones

Summary of evidence	LE
To detect residual fragments after SWL, URS or PNL, deferred imaging is more appropriate than immediate imaging post intervention.	3

Recommendation	Strength rating
Perform imaging after shock wave lithotripsy, ureteroscopy or percutaneous antegrade ureteroscopy to determine presence of residual fragments.	Strong

3.4.14.Management of specific patient groups

3.4.14.1.Management of urinary stones and related problems during pregnancy

Clinical management of a pregnant urolithiasis patient is complex and demands close collaboration between patient, radiologist, obstetrician and urologist. For diagnostic imaging see Section 3.3.1.

If spontaneous passage does not occur, or if complications develop (e.g., intractable symptoms, severe hydronephrosis or induction of premature labour), placement of a ureteral stent or a percutaneous nephrostomy tube is necessary as it is more effective than conservative treatment for symptom relief [366,367].

Unfortunately, these temporising therapies are often associated with poor tolerance, and they require multiple exchanges during pregnancy, due to the potential for rapid encrustation [368].

Ureteroscopy has become a reasonable alternative in these situations [359,369]. When compared to temporary ureteral JJ stenting until after delivery, ureteroscopy resulted in fewer needs for stent exchange, less irritative LUTS and better patient satisfaction [370].

Non-urgent ureteroscopy in pregnant women should be best performed during the second trimester, by an experienced urologist. Counselling of the patient should include access to neonatal and obstetric services [73].

Although feasible, percutaneous removal of renal stones during pregnancy remain an individual decision and should be performed only in experienced centres [371]. Pregnancy remains an absolute contraindication for SWL.

3.4.14.1.1.Summary of evidence and guideline for the management of urinary stones and related problems during pregnancy

Summary of evidence	LE
Stent insertion seems to be more effective than conservative treatment in the management of symptomatic moderate to severe hydronephrosis during pregnancy.	1b
Ureteroscopy is a reasonable alternative to avoid long-term stenting/drainage.	1a
There is a higher tendency for stent encrustation during pregnancy.	3

Recommendation	Strength rating
Treat all uncomplicated cases of urolithiasis in pregnancy conservatively (except when there are clinical indications for intervention).	Strong

3.4.14.2.Management of stones in patients with urinary diversion

Aetiology

Patients with urinary diversion are at high risk for stone formation in the renal collecting system and ureter or in the conduit or continent reservoir [372-374]. Metabolic factors (hypercalciuria, hyperoxaluria and hypocitraturia), infection with urease-producing bacteria, foreign bodies, mucus secretion, and urinary stasis are responsible for stone formation [375] (Section 3.1.3). One study has shown that the risk for recurrent upper tract stones in patients with urinary diversion subjected to PNL was 63% at five years [376].

Management

Smaller upper-tract stones can be treated effectively with SWL [204,377]. In the majority of cases, endourological techniques are necessary to achieve stone-free status [201]. In individuals with long, tortuous conduits or with invisible ureter orifices, a retrograde endoscopic approach might be difficult or impossible.

3.4.14.2.1.Summary of evidence and guideline for the management of stones in patients with urinary diversion

Summary of evidence	LE
The choice of access depends on the feasibility of orifice identification in the conduit or bowel reservoir. Whenever a retrograde approach is impossible, percutaneous access with antegrade ureteroscopy is the alternative.	4

Recommendation	Strength rating
Perform percutaneous lithotomy to remove large renal stones in patients with urinary diversion, as well as for ureteral stones that cannot be accessed via a retrograde approach, or that are not amenable to shock wave lithotripsy.	Strong

For stones in the conduit, a trans-stomal approach can be used to remove all stone material (along with the foreign body) using standard techniques, including intracorporeal lithotripsy and flexible endoscopes. Trans-stomal manipulations in continent urinary diversion must be performed carefully to avoid disturbance of the continence mechanism [378].

Before considering any percutaneous approach in these cases, CT should be undertaken to assess the presence of an overlying bowel, which could make this approach unsafe [379], and if present, an open surgical approach should be considered.

Prevention

Recurrence risk is high in these patients [376]. Metabolic evaluation and close follow-up are necessary to obtain the risk parameters for effective long-term prevention. Preventive measures include medical management of metabolic abnormalities, appropriate therapy of urinary infections, and hyperdiuresis or regular irrigation of continent reservoirs [380].

3.4.14.3.Management of stones in patients with neurogenic bladder

Aetiology, clinical presentation and diagnosis

Patients with neurogenic bladder develop urinary calculi because of additional risk factors such as bacteriuria, hydronephrosis, VUR, renal scarring, lower urinary tract reconstruction, and thoracic spinal defect [381]. The most common causes are urinary stasis and infection (Section 3.1.3). Indwelling catheters and surgical interposition of bowel segments for treatment of bladder dysfunction both facilitate UTI. Although calculi can form at any level of the urinary tract, they occur more frequently in the bladder; especially if bladder augmentation has been performed [382,383].

Diagnosis of stones may be difficult and delayed in the absence of clinical symptoms due to sensory impairment and vesico-urethral dysfunction. Difficulties in self-catheterisation should lead to suspicion of bladder calculi. Imaging studies are needed (US, CT) to confirm the clinical diagnosis prior to surgical intervention.

Management

Management of calculi in patients with neurogenic bladder is similar to that described in Section 3.3.3. In myelomeningocele patients, latex allergy is common; therefore, appropriate measures need to be taken regardless of the treatment [384]. Any surgery in these patients must be performed under general anaesthesia because of the impossibility of using spinal anaesthesia. Bone deformities often complicate positioning on the operating table [385]. The risk of stone formation after augmentation cystoplasty in immobile patients with sensory impairment can be significantly reduced by irrigation protocols [380].

For efficient long-term stone prevention in patients with neurogenic bladder, correction of the metabolic disorder, appropriate infection control, and restoration of normal storing/voiding function of the bladder are needed.

3.4.14.3.1.Summary of evidence and guideline for the management of stones in patients with neurogenic bladder

Summary of evidence	LE
Patients undergoing urinary diversion and/or suffering from neurogenic bladder dysfunction are at risk for recurrent stone formation.	3

Recommendation	Strength rating
Take appropriate measures regardless of the treatment provided since in myelomeningocele patients latex allergy is common.	Strong

3.4.14.4.Management of stones in patients with transplanted kidneys

Stones in transplanted kidneys can either be transplanted or present de novo allograft stones. Usually they are detected by routine US examination, followed by NCCT in cases of unclear diagnosis [386].

Aetiology

Transplant patients depend on their solitary kidney for renal function. Impairment causing urinary stasis/obstruction therefore requires immediate intervention or drainage of the transplanted kidney. Risk factors for de novo stone formation in these patients are multifold:

Immunosuppression increases the infection risk, resulting in recurrent UTIs.
Hyper filtration, excessively alkaline urine, renal tubular acidosis (RTA), and increased serum calcium caused by persistent tertiary hyperparathyroidism [387] are biochemical risk factors.

Stones in kidney allografts have an incidence of 1% [388].

Management

Selecting the appropriate technique for stone removal in a transplanted kidney is difficult, although management principles are similar to those applied in other single renal units [389-391]. Additional factors such as transplant function, coagulative status, and anatomical obstacles due to the iliacal position of the organ, directly influence the surgical strategy.

For large or ureteral stones, careful percutaneous access and subsequent antegrade endoscopy are more favourable. The introduction of small flexible ureteroscopes and the holmium laser has made URS a valid treatment option for transplant calculi. However, one must be aware of potential injury to adjacent organs [391-393]. Retrograde access to transplanted kidneys is difficult due to the anterior location of the ureteral anastomosis, and ureteral tortuosity [394-396].

3.4.14.4.1.Summary of evidence and guideline for the management of stones in patients with transplanted kidneys

Summary of evidence	LE
Conservative treatment for small asymptomatic stones is only possible under close surveillance and in absolutely compliant patients.	3
Shock wave lithotripsy for small calyceal stones is an option with minimal risk of complication, but localisation of the stone can be challenging and SFRs are poor.	4

Recommendation	Strength rating
Offer patients with transplanted kidneys, any of the contemporary management options, including shock wave lithotripsy, flexible ureteroenoscopy and percutaneous nephrolithotomy.	Weak

3.4.14.5.Special problems in stone removal

Table 3.8: Special problems in stone removal

Calyceal diverticulum stones	SWL, PNL [397] (if possible) or RIRS [397,398]. Can also be removed using laparoscopic retroperitoneal surgery [399-402]. Patients may become asymptomatic due to stone disintegration (SWL), whilst well-disintegrated stone material remains in the original position due to narrow calyceal neck.
Horseshoe kidneys	Can be treated in line with the options described above [403]. Passage of fragments after SWL might be poor. Acceptable SFRs can be achieved with flexible ureteroscopy.
Stones in pelvic kidneys	SWL, RIRS, PNL or laparoscopic surgery. In obese patients, the options are RIRS, PNL or open surgery.
Stones formed in a continent reservoir	Each stone must be considered and treated individually.
Patients with obstruction of the ureteropelvic junction	When outflow abnormality requires correction, stones can be removed by PNL together with percutaneous endopyelotomy or open/laparoscopic reconstructive surgery. URS together with endopyelotomy with Ho:YAG laser. Incision with an Acucise® balloon catheter might be considered, provided the stones can be prevented from falling into the pelvi-ureteral incision [404-407]. Open surgery with correction of the ureteropelvic junction obstruction (pyeloplasty) and stone removal is a feasible option [408].

3.4.15.Management of stones in children

The true incidence of nephrolithiasis in children remains unclear due to the global lack of large epidemiological studies. Data derived from nation-wide epidemiological studies [409], studies performed in different counties worldwide [410-412], and large-scale databases [413,414] indicate that the incidence and prevalence of paediatric urinary stone disease has increased over the last decades. Although boys are most commonly affected in the first decade of life [415] the greatest increase in incidence has been seen in older female adolescences [410,411,416].

Stone composition is similar in children as in adults, with predominance of calcium oxalate stones [417]. Compared to historical data, metabolic abnormalities responsible for stone formation are less commonly identified in children nowadays [418-420]. Hypocitraturia, low urine volume and hypercalciuria predominate [82,418-420]. Age may affect the predominant metabolic abnormality with hypercalciuria and hypocitraturia being the most common disorder present in children < 10 and > 10 years old, respectively [420]. Genetic or systemic diseases (e.g. cystinuria or nephrocalcinosis) contributing to stone formation are rare in children accounting for less than 17% of the identifying causes [418,421]. The role of diet remains unclear in children, although there is some evidence that children are drinking less water and taking greater daily amounts of sodium than is recommended [422-424].

For diagnostic procedures see Section 3.3.3.2, for acute decompression see Section 3.4.2. and for metabolic evaluation see Chapter 4.

3.4.15.1.Clinical presentation

Children with urinary stones can be asymptomatic or present with non-specific symptoms that necessitate a high index of suspicion for proper diagnosis [425]. Symptoms are age-dependent with infants presenting with crying, irritability and vomiting in 40% of cases [426] while in older children flank pain, micro or gross-haematuria and recurrent UTIs are more common [427,428].

3.4.15.2.Conservative management

There is a lack of evidence on conservative management of paediatric stones with evidence for ureteric calculi coming from the placebo arms of medical expulsive trials, while evidence for renal stones comes from small cohort studies, either on primary stones [429,430] or residual fragments remained after SWL, RIRS or PNL [431]. Expectant management for single, asymptomatic lower-pole renal stones could be the initial approach with increased odds of stone passage, especially in patients with non-struvite, non-cystine stones < 7 mm, with no anatomic abnormalities [429]. Intervention may be needed for stones located elsewhere independently of their size [429-431].

3.4.15.3.Medical expulsive therapy in children

There are limited studies on MET as off-label expulsive therapy for children with stones which show conflicting outcomes. A recent meta-analysis (MA) of five trials showed that adrenergic a-antagonists (tamsulosin 0.2-0.4 mg/day and doxazosin 0.03/mg/kg/day) are effective for MET increasing SFR compared to control (OR = 2.7, p = 0.001) without significantly increasing the treatment-emergent adverse events (OR = 2.01, p = 0.17) [432]. Similarly, an updated systematic review of six placebo-controlled studies showed that a-blockers might increase SFR of distal ureteric stones (RR: 1.34, 95% CI: 1.16 to 1.54; low-quality evidence) [433]. Due to study limitations and very serious imprecision, no conclusion could be drawn regarding the effect of MET on hospital stay, pain episodes or secondary procedures for residual fragments after definitive stone treatment [433].

3.4.15.4.Extracorporeal shock wave lithotripsy

Shock wave lithotripsy is still the first-line treatment for most ureteral stones in children. However, it is less likely to be successful for stones > 10 mm in diameter, impacted stones, calcium oxalate monohydrate or cystine stones, or for stones in children with unfavourable anatomy and in whom localisation is difficult [434].

Studies on extracorporeal SWL in children suggest an overall SFR of 70-90%, retreatment rate of 4-50% and need for auxiliary procedures in 4-12.5% of cases [435-439]. A MA of 14 studies reporting on 1,842 paediatric patients treated with SWL found significantly higher SFR for stones < 10 mm than for stones > 10 mm and higher retreatment rates as the stone size increased [434]. For best clinical practice see Section 3.4.5. A recent MA on slow SWL vs. rapid SWL for renal stones revealed very low-quality evidence about the effects of SWL on SFRs, serious adverse events or complications of treatment and secondary procedures for residual fragments [433]. Shock wave lithotripsy is well tolerated by children with complication rates rising up to 15% in modern series, mostly in the form of ureteral obstruction secondary to steinstrasse formation [440]. However, good treatment outcomes are more likely to require the administration of general anaesthesia to children. With improvements in modern (second and third generation) lithotripters, successful treatment using intravenous sedation, patient-controlled analgesia or no medication at all has been increasingly performed in a select population of older, co-operative children [441].

Based on the results of a recent MA which compared SWL to dissolution therapy for intrarenal stones, and SWL to ureteroscopy with holmium laser or pneumatic lithotripsy for renal and distal ureteric stones, no firm conclusions can be drawn about the effects of SWL on SFR, serious adverse events or complications of treatment and secondary procedures for residual fragments [433].

When SWL was compared to mini-percutaneous nephrolithotripsy for lower pole renal stones 1-2 cm in size SWL resulted in lower SFRs (RR: 0.88, 95% CI: 0.80 to 0.97; moderate quality evidence) and higher rates of secondary procedures (RR: 2.50, 95% CI: 1.01 to 6.20; low-quality evidence); however, SWL showed less severe adverse events (RR: 0.13, 95% CI: 0.02 to 0.98; low quality evidence) [442].

3.4.15.5.Endourological procedures

Rigid/semi-rigid ureteroscopy

In recent years ureteroscopy is increasingly used in children with ureteral stones [443]. Ureteroscopy proved to be effective with SFR of 81-98% [444-446], retreatment rates of 6.3%-10% [444,447] and complication rates of 1.9-23% [444-446,448]. Similar to adults, routine stenting is not necessary before URS. However, pre-stenting may facilitate URS, increase SFR and decrease complication rates [449]. Stenting after URS is a strong predictor of retreatment requiring anaesthesia in children [450].

Flexible ureteroscopy/retrograde intrarenal surgery

Retrograde intra-renal surgery (FURS) with flexible ureteroscopes has become an efficacious treatment modality for paediatric renal stones. Recent studies report SFRs of 76-100%, retreatment rates of 0-19% and complication rates of 0-28% [451-456]. Younger age, cystine composition [457], large stone diameter [456] and lack of pre-stenting predispose to FURS failure in children [449].

Although high level of evidence is lacking to support strong recommendation [433], FURS may
be a particularly effective treatment option for lower calyx stones in the presence of unfavourable factors
for SWL [446,453,458].

For large and complex kidney stones RIRS has a significantly lower SFR compared to PNL (71% vs. 95%), but is associated with less radiation exposure, lower complication rates and a shorter hospital stay [459].

Similarly, retrospectively data indicate that RIRS may achieve lower SFRs compared to mini- or micro- percutaneous surgery in favour of shorter operative time, shorter fluoroscopy time and less hospitalisation time [460,461]. A recently published MA confirmed the aforementioned results [462].

Percutaneous nephrolithotomy

Indications for PNL in children are similar to those in adults, and include renal stones > 2 cm, or smaller stones resistant to SWL and ureteroscopic treatment. Reported SFRs with paediatric PNL are 71.4-95% after a single session [459-461,463-465] with an overall complication rate of 20% [466]. High degree of hydronephrosis, increased number of tracts and operative time [467] and large tract size [465,468-470] are associated with increased blood loss. Child age [469] and stone burden [465] predispose to the use of larger instruments during PNL in children. Miniaturisation of equipment increases the opportunity to perform tubeless PNL in appropriately selected children, which can reduce the length of hospital stay and post-operative pain [471,472].

Concerns have been raised regarding possible adverse effects of PNL on the renal parenchyma of the developing child. However, focal damage is only reported in 5% of cases [473]. Using pre- and post-PCNL DMSA scans, Cicekbilek et al. demonstrated that PNL tracts between 12-24 Charrière in size did not cause significant harm to paediatric kidneys [463].

3.4.15.6.Open and laparoscopic/robot-assisted stone surgery

With the advances in ESWL, PNL and RIRS, very few cases of paediatric urolithiasis require open surgery. Data extracted from the National Inpatient Sample (NIS) databases for 2001-2014 showed that in the USA incisional procedures (mainly nephrolithotomy, pyelolithotomy and ureterotomy) were performed in 2.6% of the hospitalised patients (52% aged 15-17 years) who required surgical intervention for urinary stones [474]. Laparoscopy for the management of paediatric renal and ureteric stones is a safe and effective procedure when specific indications are followed. Stone free rates of 100% were reported when laparoscopic pyelolithotomy was applied for a ≥1cm single stone located in an extrarenal pelvis [475] or when laparoscopic ureterolithotomy was applied to impacted ureteric stones ≥1.5 cm or to ureteric stones that were refractory to SWL or URS [476]. There are extremely limited data available on efficacy and complications of robot-assisted laparoscopic management of paediatric urolithiasis [477].

3.4.15.7.Special considerations on recurrence prevention

All paediatric stone formers need metabolic evaluation and recurrence prevention with respect to the detected stone type. Children are in the high-risk group for stone recurrence (See Chapter 4).

3.4.15.8.Summary of evidence and guidelines for the management of stones in children

Summary of evidence	LE
In children, the indications for SWL, URS and PNL are similar to those in adults.	1b

Recommendations	Strength rating
Offer children with single ureteral stones less than 10 mm shock wave lithotripsy (SWL) if localisation is possible as first line option.	Strong
Ureteroscopy is a feasible alternative for ureteral stones not amenable to SWL.	Strong
Offer children with renal stones with a diameter of up to 20 mm (~300 mm2) SWL.	Strong
Offer children with renal pelvic or calyceal stones with a diameter > 20 mm (~300 mm2) percutaneous nephrolithotomy.	Strong
Retrograde renal surgery is a feasible alternative for renal stones smaller than 20 mm in all locations.	Weak

4.FOLLOW UP: METABOLIC EVALUATION AND RECURRENCE PREVENTION

4.1.General metabolic considerations for patient work-up

4.1.1.Evaluation of patient risk

After stone passage, every patient should be assigned to a low- or high-risk group for stone formation (Figure 4.1). For correct classification, two items are mandatory:

reliable stone analysis by infrared spectroscopy or X-ray diffraction;
basic analysis (Section 3.3.2).

Only high-risk stone formers require specific metabolic evaluation. Stone type is the deciding factor for further diagnostic tests. The different stone types include:

calcium oxalate;
calcium phosphate;
uric acid;
ammonium urate;
struvite (and infection stones);
cystine;
xanthine;
2,8-Dihydroxyadenine;
drug stones;
stones of unknown composition.

Figure 4.1: Assignment of patients to low- or high-risk groups for stone formation

4.1.2.Urine sampling

Specific metabolic evaluation requires collection of two consecutive 24-hour urine samples [478,479]. The collecting bottles should be prepared with 5% thymol in isopropanol or stored at < 8°C during collection to prevent the risk of spontaneous crystallisation in the urine [480,481]. Pre-analytical errors can be minimised by carrying out urinalysis immediately after collection. Alternatively, boric acid (10 g powder per urine container) can also be used. The collecting method should be chosen in close cooperation with the particular laboratory. Urine pH should be assessed during collection of freshly voided urine four times daily using sensitive pH-dipsticks or a pH-meter [22,480].

Spot urine samples are an alternative method of sampling, particularly when 24-hour’s urine collection is difficult, for example, in non-toilet trained children [482]. Spot urine studies normally link the excretion rates to creatinine [482], but these are of limited use because the results may vary with collection time and patients’ sex, body weight and age.

4.1.3.Timing of specific metabolic work-up

For the initial specific metabolic work-up, the patient should stay on a self-determined diet under normal daily conditions and should ideally be stone free for at least twenty days [483]. Follow-up studies are necessary in patients taking medication for recurrence prevention [484]. The first follow-up 24-hour urine measurement is suggested eight to twelve weeks after starting pharmacological prevention of stone recurrence. This enables drug dosage to be adjusted if urinary risk factors have not normalised, with further 24-hour urine measurements, if necessary. Once urinary parameters have been normalised, it is sufficient to perform 24-hour urine evaluation every twelve months. The Panel realise that on this issue there is only very limited published evidence, and aim to set up a SR on the ideal timing of the 24-hour urine collection.

4.1.4.Reference ranges of laboratory values

Tables 4.1 - 4.4 provide the internationally accepted reference ranges for the different laboratory values in serum and urine.

Table 4.1: Normal laboratory values for blood parameters in adults [484,485]

Blood parameter	Reference range
Creatinine	20-100 μmol/L
Sodium	135-145 mmol/L
Potassium	3.5-5.5 mmol/L
Calcium	2.0-2.5 mmol/L (total calcium)
	1.12-1.32 mmol/L (ionised calcium)
Uric acid	119-380 μmol/L
Chloride	98-112 mmol/L
Phosphate	0.81-1.29 mmol/L
Blood gas analysis	pH	7.35-7.45
	pO2	80-90 mmHg
	pCO2	35-45 mmHg
	HCO3	22-26 mmol/L
	BE	± 2 mmol/L

BE = base excess (loss of buffer base to neutralise acid); HCO = bicarbonate; PCO = partial pressure of carbon >dioxide; PO = partial pressure of oxygen.

4.1.5.Risk indices and additional diagnostic tools

Several risk indices have been developed to describe the crystallisation risk for calcium oxalate or calcium phosphate in urine [486-489]. However, clinical validation of these risk indices for recurrence prediction or therapy improvement is ongoing.

Table 4.2: Normal laboratory values for urinary parameters in adults

Urinary Parameters	Reference ranges and limits for medical attention
pH	Constantly > 5.8 (suspicious of renal tubular acidosis)
	Constantly > 7.0 (suspicious of infection)
	Constantly < 5.8 (suspicious of acidic arrest)
Specific weight	> 1.010
Creatinine	7-13 mmol/day females
Creatinine	13-18 mmol/day males
Calcium	> 5.0 mmol/day (see Fig. 4.2)
Calcium	> 8.0 mmol/day (see Fig. 4.2)
Oxalate	> 0.5 mmol/day (suspicious of enteric hyperoxaluria)
Oxalate	> 1.0 mmol/day (suspicious of primary hyperoxaluria)
Uric acid	> 4.0 mmol/day (females), 5 mmol/day (males)
Citrate	< 2.5 mmol/day
Magnesium	< 3.0 mmol/day
Inorganic phosphate	> 35 mmol/day
Ammonium	> 50 mmol/day
Cystine	> 0.8 mmol/day

Table 4.3: Normal values for spot urine samples: creatinine ratios (solute/creatinine) in adults [490]

Parameter/Patient age	Ratio of solute to creatinine	Units
Calcium	mol/mol	mg/mg
< 12 months	< 2.0	0.81
1-3 years	< 1.5	0.53
1-5 years	< 1.1	0.39
5-7 years	< 0.8	0.28
> 7 years	< 0.6	0.21
Oxalate	mol/mol	mg/mg
0-6 months	< 325-360	288-260
7-24 months	< 132-174	110-139
2-5 years	< 98-101	80
5-14 years	< 70-82	60-65
> 16 years	< 40	32
Citrate	mol/mol	g/g
0-5 years	> 0.25	0.42
> 5 years	> 0.15	0.25
Magnesium	mol/mol	g/g
	> 0.63	> 0.13
Uric acid
> 2 years	< 0.56 mg/dL (33 imol/L) per GFR (ratio x plasma creatinine)

Table 4.4: Solute excretion in 24-hour urine samples in children [490,491]*

Calcium/24 hour	Citrate/24 hour		Cystine/24 hour		Oxalate/24 hour		Urate/24 hour
All age groups	Boys	Girls	< 10 years	> 10 years	All age groups	< 1 year	1-5 years	> 5 years
< 0.1 mmol/kg/ 24 h	> 1.9 mmol/ 1.73 m2/24 h	> 1.6 mmol/ 1.73 m2/24 h	< 55 μmol/ 1.73 m2/ 24 h	< 200 μmol/ 1.73 m2/ 24 h	< 0.5 mmol/ 1.73 m2/ 24 h	< 70 μmol/kg/ 24 h	< 65 mμmol/kg/ 24 h	< 55 μmol/kg/ 24 h
< 4 mg/kg/24 h	> 365 mg/ 1.73 m2/24 h	> 310 mg/ 1.73 m2/24 h	< 13 mg/ 1.73 m2/24 h	< 48 mg/ 1.73 m2/24 h	< 45 mg / 1.73 m2/24 h	< 13 mg/ kg/24 h	< 11 mg/ kg/24 h	< 9.3 mg/kg/24 h

*24 h urine parameters are diet and gender dependent and may vary geographically.

4.2.General considerations for recurrence prevention

All stone formers, independent of their individual risk, should follow the preventive measures in Table 4.5. The main focus is normalisation of dietary habits and lifestyle risks. Stone formers at high risk need specific prophylaxis for recurrence, which is usually pharmacological treatment based on stone analysis.

Table 4.5: General preventive measures

Fluid intake (drinking advice)	Fluid amount: 2.5-3.0 L/day
	Circadian drinking
	Neutral pH beverages
	Diuresis: 2.0-2.5 L/day
	Specific weight of urine: < 1010 g/day
Nutritional advice for a balanced diet	Balanced diet*
	Rich in vegetables and fibre
	Normal calcium content: 1-1.2 g/day
	Limited NaCl content: 4-5 g/day
	Limited animal protein content: 0.8-1.0 g/kg/day
Lifestyle advice to normalise general risk factors	BMI: retain a normal BMI level
	Adequate physical activity
	Balancing of excessive fluid loss

Caution: Protein requirements are age dependent; therefore, protein restriction in childhood should be handled carefully.

* Avoid excessive consumption of vitamin supplements.

4.2.1.Fluid intake

An inverse relationship between high fluid intake and stone formation has been repeatedly demonstrated [492-494]. The effect of fruit juices is mainly determined by the presence of citrate or bicarbonate [495]. If hydrogen ions are present, the net result is neutralisation. However, if potassium is present, both pH and citrate are increased [496,497]. One large fair-quality RCT randomly assigned men with more than one past renal stone of any type and soft drink consumption of at least 160 mL/day to reduced soft drink intake or no treatment. Although the intervention significantly reduced the risk for symptomatic recurrent stones (RR: 0.83; CI: 0.71- 0.98), the level of evidence for this outcome is low because results were from only one trial [494,498].

4.2.2.Diet

A common sense approach to diet should be taken, that is, a mixed, balanced diet with contributions from all food groups, without any excesses [494,499,500]. Fruits, vegetables and fibre: fruit and vegetable intake should be encouraged because of the beneficial effects of fibre, although the role of the latter in preventing stone recurrences is debatable [501-504]. The alkaline content of a vegetarian diet also increases urinary pH.

Oxalate: excessive intake of oxalate-rich products should be limited or avoided to prevent high oxalate load [495], particularly in patients who have high oxalate excretion.

Vitamin C: although vitamin C is a precursor of oxalate, its role as a risk factor in calcium oxalate stone formation remains controversial [505]. However, it seems wise to advise calcium oxalate stone formers to avoid excessive intake.

Animal protein: animal protein should not be consumed in excess [506,507] and limited to 0.8-1.0 g/kg body weight. Excessive consumption of animal protein has several effects that favour stone formation, including hypocitraturia, low urine pH, hyperoxaluria and hyperuricosuria.

Calcium intake: calcium should not be restricted, unless there are strong reasons for doing so, due to the inverse relationship between dietary calcium and stone formation [502,508]. The daily requirement for calcium is 1,000 to 1,200 mg [22]. Calcium supplements are not recommended except in enteric hyperoxaluria, when additional calcium should be taken with meals to bind intestinal oxalate [494,507,509]. Older adults who do not have a history of renal stones but who take calcium supplements should ensure adequate fluid intake since it may prevent increases in urine calcium concentration, and thereby reduce or eliminate any increased risk of renal stones formation associated with calcium supplement use [510].

Sodium: daily sodium (NaCl) intake should not exceed 3-5 g [22]. High intake adversely affects urine composition:

calcium excretion is increased by reduced tubular reabsorption;
urinary citrate is reduced due to loss of bicarbonate;
increased risk of sodium urate crystal formation.

Calcium stone formation can be reduced by restricting sodium and animal protein [506,507]. A positive correlation between sodium consumption and risk of first-time stone formation has been confirmed only in women [508,511]. There have been no prospective clinical trials on the role of sodium restriction as an independent variable in reducing the risk of stone formation.

Urate: intake of purine-rich food should be restricted in patients with hyperuricosuric calcium oxalate [512,513] and uric acid stones. Intake should not exceed 500 mg/day [22].

4.2.3.Lifestyle

Lifestyle factors may influence the risk of stone formation, for example, obesity [514] and arterial
hypertension [515,516].

4.2.4.Summary of evidence and guideline for recurrence prevention

Summary of evidence	LE
Increasing fluid intake reduces the risk of stone recurrence.	1a

Recommendation	Strength rating
Advise patients that a generous fluid intake is to be maintained, allowing for a 24-hour urine volume > 2.5 L.	Strong

4.3.Stone-specific metabolic evaluation and pharmacological recurrence prevention

4.3.1.Introduction

Pharmacological treatment is necessary in patients at high risk for recurrent stone formation. The ideal drug should halt stone formation, have no side effects, and be easy to administer. Each of these aspects is important to achieve good compliance. Table 4.6 highlights the most important characteristics of commonly used medication.

Table 4.6: Pharmacological substances used for stone prevention - characteristics, specifics and dosage

Agent	Rationale	Dose	Specifics and side effects	Stone type	Ref
Alkaline citrates	Alkalinisation Hypocitraturia Inhibition of calcium oxalate crystallisation	5-12 g/d (14-36 mmol/d) Children: 0.1-0.15 g/kg/d	Daily dose for alkalinisation depends on urine pH	Calcium oxalate Uric acid Cystine	[57,494,517-524]
Allopurinol	Hyperuricosuria Hyperuricaemia	100-300 mg/d Children: 1-3 mg/kg/d	100 mg in isolated hyperuricosuria Renal insufficiency demands dose correction	Calcium oxalate Uric acid Ammonium urate 2,8-Dihydroxyadenine	[525-529]
Calcium	Enteric hyperoxaluria	1000 mg/d	Intake 30 min before meals	Calcium oxalate	[507-509]
Captopril	Cystinuria Active decrease of urinary cystine levels	75-150 mg	Second-line option due to significant side effects	Cystine	[530,531]
Febuxostat	Hyperuricosuria Hyperuricaemia	80-120 mg/d	Acute gout contraindicated, pregnancy, xanthine stone formation	Calcium oxalate Uric acid	[532,533]
L-Methionine	Acidification	600-1500 mg/d	Hypercalciuria, bone demineralisation, systemic acidosis. No long-term therapy	Infection stones Ammonium urate Calcium phosphate	[57,534,535]
Magnesium	Isolated hypomagnesiuria Enteric hyperoxaluria	200-400 mg/d Children: 6 mg/kg/d	Renal insufficiency demands dose correction. Diarrhoea, chronic alkali losses, hypocitraturia	Calcium oxalate	[536,537] (Low evidence)
Sodium bicarbonate	Alkalinisation Hypocitraturia	4.5 g/d	-	Calcium oxalate Uric acid, Cystine	[538]
Pyridoxine	Primary hyperoxaluria	Initial dose 5 mg/kg/d Max. 20 mg/kg/d	Polyneuropathia	Calcium oxalate	[539]
Thiazide (Hydrochlorothiazide)	Hypercalciuria	25-50 mg/d Children: 0.5-1 mg/kg/d	Risk for agent-induced hypotonic blood pressure, diabetes, hyperuricaemia, hypokalaemia, followed by intracellular acidosis and hypocitraturia	Calcium oxalate Calcium phosphate	[57,536,540-548]
Tiopronin	Cystinuria Active decrease of urinary cystine levels	Initial dose 250 mg/d	Max. 2000 mg/d Risk for tachyphylaxis and proteinuria	Cystine	[549-552]

4.4.Calcium oxalate stones

The criteria for identification of calcium oxalate stone formers with high recurrence risk are listed in Chapter 3.1.2.

4.4.1.Diagnosis

Blood analysis requires measurement of creatinine, sodium, potassium, chloride, ionised calcium (or total calcium + albumin), uric acid, and parathyroid hormone (PTH) (and vitamin D) in the case of increased calcium levels. Urinalysis requires measurement of urine volume, urine pH profile, specific weight, calcium, oxalate, uric acid, citrate, sodium and magnesium.

4.4.2.Interpretation of results and aetiology

The diagnostic and therapeutic algorithm for calcium oxalate stones is shown in Figure 4.2 [57,494,518-520,525-527,532,536-538,540-547,553-557].

The most common metabolic abnormalities associated with calcium stone formation are hypercalciuria, which affects 30-60% of adult stone formers, and hyperoxaluria (26-67%), followed by hyperuricosuria (15-46%), hypomagnesiuria (7-23%), and hypocitraturia (5-29%). However, ranges tend to differ based on ethnicity [553].

Elevated levels of ionised calcium in serum (or total calcium and albumin) require assessment of intact PTH to confirm or exclude suspected hyperparathyroidism (HPT).
“Acidic arrest” (urine pH constantly < 5.8) may promote co-crystallisation of uric acid and calcium oxalate.
Similarly, increased uric acid excretion (> 4 mmol/day in adults or > 12 mg/kg/day in children) can act as a promoter.
Urine pH levels constantly > 5.8 in the day profile indicate RTA, provided UTI has been excluded. An ammonium chloride loading test confirms RTA and identifies RTA subtype (Section 4.6.5).
Hypercalciuria may be associated with normocalcemia (idiopathic hypercalciuria, or granulomatous diseases) or hypercalcaemia (hyperparathyroidism, granulomatous diseases, vitamin D excess, or malignancy).
Hypocitraturia (male < 1.7 mmol/d, female < 1.9 mmol/d) may be idiopathic or secondary to metabolic acidosis or hypokalaemia.
Oxalate excretion > 0.5 mmol/day in adults (> 0.37 mmol/1.73 m2/day in children) confirms hyperoxaluria.
primary hyperoxaluria (oxalate excretion mostly > 1 mmol/day), appears in three genetically determined forms;

secondary hyperoxaluria (oxalate excretion > 0.5 mmol/day, usually < 1 mmol/day), occurs due to intestinal hyperabsorption of oxalate or extreme dietary oxalate intake;

mild hyperoxaluria (oxalate excretion 0.45-0.85 mmol/day), commonly found in idiopathic calcium oxalate stone formers.
Hypermagnesiuria (< 3.0 mmol/day) may be related to poor dietary intake or to reduced intestinal absorption (chronic diarrhoea).

Figure 4.2: Diagnostic and therapeutic algorithm for calcium oxalate stones

1 Be aware of excess calcium excretion.
2 tid = three times/day (24h).
3 No magnesium therapy for patients with renal insufficiency.
4 There is no evidence that combination therapy (thiazide + citrate) or (thiazide + allopurinol) is superior to thiazide therapy alone [511,518].
5 Febuxostat 80 mg/d.

4.4.3.Specific treatment

General preventive measures are recommended for fluid intake and diet. Hyperoxaluric stone formers should consume foods with low oxalate content, whereas hyperuricosuric stone formers benefit from daily dietary reduction of purine. Figure 4.2 summarises the diagnostic algorithm and the pharmacological treatment of calcium oxalate stones [57,494,497,518-520,525-527,532,536-538,540-547,553-557]. There is only low level evidence on the efficacy of preventing stone recurrence through pretreatment stone composition examination and biochemistry measures, or on-treatment biochemistry measures [494].

4.4.4.Summary of evidence and guidelines for pharmacological treatments for patients with specific abnormalities in urine composition (based on 24-hour urine samples)

Summary of evidence	LE
Thiazide + potassium citrate can reduce stone formation.	1a
Oxalate restriction is beneficial if hyperoxaluria is present.	2b
Potassium citrate can reduce stone formation in enteric hyperoxaluria.	3-4
Calcium supplement can reduce stone formation in enteric hyperoxaluria.	2
Diet reduced in fat and oxalate can be beneficial in reducing stone formation.	3
Potassium citrate and sodium bicarbonate can be used to if hypocitraturia is present.	1b
Allopurinol is first-line treatment of hyperuricosuria.	1a
Febuxostat is second-line treatment of hyperuricosuria.	1b
Avoid excessive intake of animal protein in hyperuricosuria.	1b
Restricted intake of salt is beneficial if there is high urinary sodium excretion.	1b

Recommendations	Strength rating
Prescribe thiazide + potassium citrate in case of hypercalcuria.	Strong
Advise oxalate restriction if hyperoxaluria is present.	Weak
Offer potassium citrate in enteric hyperoxaluria.	Weak
Offer calcium supplement in enteric hyperoxaluria.	Weak
Advise reduced dietary fat and oxalate in enteric hyperoxaluria.	Weak
Prescribe potassium citrate and sodium bicarbonate in case of hypocitraturia.	Strong
Prescribe allopurinol in case of hyperuricosuria.	Strong
Offer febuxostat as second-line treatment of hypericosuria.	Strong
Advise avoiding excessive intake of animal protein in hypericosuria.	Strong
Advise restricted intake of salt if there is high urinary sodium excretion.	Strong

4.5.Calcium phosphate stones

Some calcium phosphate stone formers are at high risk of recurrence. Further information on identifying high-risk patients is provided in Section 3.1.2.

Calcium phosphate mainly appears in two completely different minerals: carbonate apatite and brushite. Carbonate apatite crystallisation occurs at a pH > 6.8 and may be associated with infection.

Brushite crystallises at an optimum pH of 6.5-6.8, at high urinary concentrations of calcium (> 8 mmol/day) and phosphate (> 35 mmol/day). Its occurrence is not related to UTI. Possible causes of calcium phosphate stones include HPT, RTA and UTI; each of which requires different therapy.

4.5.1.Diagnosis

Diagnosis requires blood analysis for: creatinine, sodium, potassium, chloride, ionised calcium (or total calcium + albumin), and PTH (in the case of increased calcium levels). Urinalysis includes measurement of: volume, urine pH profile, specific weight, calcium, phosphate and citrate.

4.5.2.Interpretation of results and aetiology

General preventative measures are recommended for fluid intake and diet. The diagnostic and therapeutic algorithm for calcium phosphate stones is shown in Figure 4.3.

Figure 4.3: Diagnostic and therapeutic algorithm for calcium phosphate stones

HPT = hyperparathyroidism; RTA = renal tubular acidosis; UTI = urinary tract infection.

4.5.3.Pharmacological therapy [57,494,540,541,545,557]

Hyperparathyroidism and RTA are common causes of calcium phosphate stone formation. Although most patients with primary HPT require surgery, RTA can be corrected pharmacologically. If primary HPT and RTA have been excluded, pharmacotherapy for calcium phosphate calculi depends on effective reduction of urinary calcium levels using thiazides. If urine pH remains constantly > 6.2, urinary acidification with L-methionine may be beneficial; however, it is not commonly used and needs monitoring for systemic acidosis development. For infection-associated calcium phosphate stones, it is important to consider the guidance given for infection stones.

4.5.4.Summary of evidence and guidelines for the management of calcium phosphate stones

Summary of evidence	LE
Thiazide is beneficial in case of hypercalciuria.	1a
Acidification of urine can be beneficial in case of high urine pH.	3-4

Recommendations	Strength rating
Prescribe thiazide in case of hypercalciuria.	Strong
Advise patients to acidify their urine in case of high urine pH.	Weak

4.6.Disorders and diseases related to calcium stones

4.6.1.Hyperparathyroidism [558-560]

Primary HPT is responsible for an estimated 5% of all calcium stone formation. Renal stones occur in approximately 20% of patients with primary HPT. Elevated levels of parathyroid hormone (PTH) significantly increase calcium turnover, leading to hypercalcaemia and hypercalciuria. Serum calcium may be mildly elevated and serum PTH may be within the upper normal limits, therefore, repeated measurements may be needed; preferably with the patient fasting. Stones of HPT patients may contain both calcium oxalate and calcium phosphate.

If HPT is suspected, neck exploration should be performed to confirm the diagnosis. Primary HPT can only be cured by surgery.

4.6.2.Granulomatous diseases [561]

Granulomatous diseases, such as sarcoidosis, may be complicated by hypercalcaemia and hypercalciuria secondary to increased calcitriol production. The latter is independent of PTH control, leading to increased calcium absorption in the gastrointestinal tract and suppression of PTH. Treatment focuses on the activity of the granulomatous diseases and may require steroids, hydroxychloroquine or ketoconazole. Treatment should be reserved for a specialist.

4.6.3.Primary hyperoxaluria [539]

Patients with primary hyperoxaluria (PH) should be referred to specialised centres, as successful management requires an experienced interdisciplinary team. The main therapeutic aim is to reduce endogenous oxalate production, which is increased in patients with PH. In approximately one-third of patients with PH type I, pyridoxine therapy normalises or significantly reduces urinary oxalate excretion. The goal of adequate urine dilution is achieved by adjusting fluid intake to 3.5-4.0 L/day in adults (children 1.5 L/m2 body surface area) and following a circadian drinking regimen.

Therapeutic options for preventing calcium oxalate crystallisation include hyperdiuresis, alkaline citrates and magnesium. However, in end-stage renal failure, PH requires simultaneous liver-kidney transplantation.

Treatment regimens are:

pyridoxine in PH type I: 5-20 mg/kg/day according to urinary oxalate excretion and patient tolerance;
alkaline citrate: 9-12 g/day in adults, 0.1-0.15 meq/kg/day in children;
magnesium: 200-400 mg/day (no magnesium in the case of renal insufficiency).

4.6.3.1.Summary of evidence and guideline for the management of primary hyperoxaluria

Summary of evidence	LE
Pyridoxine can reduce the urinary oxalate excretion in primary hyperoxaluria.	3

Recommendation	Strength rating
Prescribe pyridoxine for primary hyperoxaluria.	Strong

4.6.4.Enteric hyperoxaluria [509,562]

Enteric hyperoxaluria is a particularly problematic condition in patients with intestinal malabsorption of fat. This abnormality is associated with a high risk of stone formation, and is seen after intestinal resection and malabsorptive bariatric surgery as well as in Crohn’s disease and pancreas insufficiency. In addition to hyperoxaluria, these patients usually present with hypocitraturia due to loss of alkali. Urine pH is usually low, as are urinary calcium and urine volume. All these abnormalities contribute to high levels of supersaturation with calcium oxalate, crystalluria, and stone formation. Specific preventive measures are:

restricted intake of oxalate-rich foods;
restricted fat intake;
calcium supplementation at meal times to enable calcium oxalate complex formation in the
intestine [509,562];
sufficient fluid intake to balance intestinal loss of water caused by diarrhoea;
alkaline citrates to raise urinary pH and citrate.

4.6.4.1.Summary of evidence and guidelines for the management of enteric hyperoxaluria

Summary of evidence	LE
Potassium citrate can be beneficial to replace citrate loss and raise urine pH.	3
Calcium supplements with meals can enable calcium oxalate complex formation in the intestine.	2
Reduction in dietary fat and oxalate can be beneficial in intestinal malabsorption.	3

Recommendations	Strength rating
Prescribe potassium citrate.	Weak
Advise patients to take calcium supplements with meals.	Strong
Advise patients to follow a diet with a low fat and oxalate content.	Weak

4.6.5.Renal tubular acidosis [563,564]

Renal tubular acidosis is caused by severe impairment of proton or bicarbonate handling along the nephron. Kidney stone formation most probably occurs in patients with distal RTA type I. Figure 4.4 outlines the diagnosis of RTA. Table 4.7 shows acquired and inherited causes of RTA [542-544].

Figure 4.4: Diagnosis of renal tubular acidosis

BGA = blood gas analysis; RTA = renal tubular acidosis.

** An alternative ammonium chloride loading test using NH4Cl load with 0.05 g/kg body weight over three days might provide similar results and may be better tolerated by the patient. A second alternative in these cases could be the furosemide acidification test.

Renal tubular acidosis can be acquired or inherited. Reasons for acquired RTA can be obstructive uropathy, recurrent pyelonephritis, acute tubular necrosis, renal transplantation, analgesic nephropathy, sarcoidosis, idiopathic hypercalciuria, and primary parathyroidism; it may also be drug-induced (e.g. zonisamide). Table 4.7 shows the inherited causes of RTA.

Table 4.7: Inherited causes of renal tubular acidosis

Type - inheritance	Gene/gene product/function	Phenotype
Autosomal dominant	SLC4A1/AE1/Cl-bicarbonate exchanger	Hypercalciuria, hypokalaemia, osteomalacia
Autosomal recessive with hearing loss	ATP6V1B1/B1 subunit of vacuolar H-ATPase/proton secretion	Hypercalciuria, hypokalaemia, rickets
Autosomal recessive	ATP6V0A4/A4 subunit of vacuolar H-ATPase/proton secretion	Hypercalciuria, hypokalaemia, rickets

The main therapeutic aim of RTA treatment is restoring a normal acid-base equilibrium. Despite the alkaline pH of urine in RTA, alkalinisation using alkaline citrates or sodium bicarbonate is key to normalising the metabolic changes (intracellular acidosis) responsible for stone formation (Table 4.8). The alkali load reduces tubular reabsorption of citrate, which in turn normalises citrate excretion and simultaneously reduces calcium turnover. Therapeutic success can be monitored by venous blood gas analysis (base excess: ± 2.0 mmol/L) in complete RTA. If excessive calcium excretion (> 8 mmol/day) persists after re-establishing acid-base equilibrium, thiazides may lower urinary calcium excretion.

Table 4.8: Pharmacological treatment of renal tubular acidosis

Biochemical risk factor

Rationale for pharmacological therapy

Medication

Hypercalciuria

Calcium excretion > 8 mmol/day

Hydrochlorothiazide,

- in adults: 25 mg/day initially, up to 50 mg/day

- in children: 0.5-1 mg/kg/day

Alternatives in adults:

Chlorthalidone 25 mg/d

Indapamide 2.5 mg/d

Inadequate urine pH

Intracellular acidosis in nephron

Alkaline citrate, 9-12 g/day divided in three doses

Sodium bicarbonate, 1.5 g, three

times daily

4.6.5.1.Summary of evidence and guidelines for the management of tubular acidosis

Summary of evidence	LE
Potassium citrate can be beneficial in distal renal tubular acidosis to correct the intracellular acidosis.	2b
Thiazide and potassium citrate are beneficial for hypercalciuria.	1a

Recommendations	Strength rating
Prescribe potassium citrate for distal renal tubular acidosis.	Weak
Prescribe thiazide and potassium citrate for hypercalciuria.	Strong

4.6.6.Nephrocalcinosis [490]

Nephrocalcinosis (NC) refers to increased crystal deposition within the renal cortex or medulla, and occurs alone or in combination with renal stones. There are various metabolic causes. The main risk factors are: HPT, PH, RTA, vitamin D metabolic disorders, idiopathic hypercalciuria and hypocitraturia, and genetic disorders, including Dent’s disease, Bartter’s syndrome and medullary sponge kidney. The many causes of NC means there is no single standard therapy. Therapeutic attention must focus on the underlying metabolic or genetic disease, while minimising the biochemical risk factors.

4.6.6.1.Diagnosis

Diagnosis requires the following blood analysis: PTH (in the case of increased calcium levels), vitamin D and metabolites, vitamin A, sodium, potassium, magnesium, chloride, and blood gas analysis. Urinalysis should investigate urine pH profile (minimum four times daily), daily urine volume, specific weight of urine, and levels of calcium, oxalate, phosphate, uric acid, magnesium and citrate.

4.7.Uric acid and ammonium urate stones

All uric acid and ammonium urate stone formers are considered to be at high risk of recurrence [22]. Uric acid nephrolithiasis is responsible for approximately 10% of renal stones [565] and associated with hyperuricosuria or low urinary pH. Hyperuricosuria may be a result of dietary excess, endogenous overproduction (enzyme defects), myeloproliferative disorders, tumour lysis syndrome, drugs, gout or catabolism [566]. Low urinary pH may be caused by decreased urinary ammonium excretion (insulin resistance or gout), increased endogenous acid production (insulin resistance, metabolic syndrome, or exercise-induced lactic acidosis), increased acid intake (high animal protein intake), or increased base loss (diarrhoea) [566].

Ammonium urate stones are extremely rare, comprising < 1% of all types of urinary stones. They are associated with UTI, malabsorption (inflammatory bowel disease and ileostomy diversion or laxative abuse), potassium deficiency, hypokalaemia and malnutrition. Suggestions on uric acid and ammonium urate nephrolithiasis are based on level 3 and 4 evidence.

4.7.1.Diagnosis

Figure 4.5 shows the diagnostic and therapeutic algorithm for uric acid and ammonium urate stones. Blood analysis requires measurement of creatinine, potassium and uric acid levels. Urinalysis requires measurement of urine volume, urine pH profile, specific weight of urine, and uric acid level. Urine culture is needed in the case of ammonium urate stones.

4.7.2.Interpretation of results

Uric acid and ammonium urate stones form under completely different biochemical conditions. Acidic arrest (urine pH constantly < 5.8) promotes uric acid crystallisation.

Hyperuricosuria is defined as uric acid excretion > 4 mmol/day in adults or > 0.12 mmol/kg/day in children. Hyperuricaemia may be present, but there is only weak evidence for its association with stone formation.

Hyperuricosuric calcium oxalate stone formation can be distinguished from uric acid stone formation by urinary pH, which is usually > 5.5 in calcium oxalate stone formation and < 5.5 in uric acid stone formation and occasional absence of hyperuricosuria in patients with pure uric acid stones [567,568]. Ammonium urate crystals form in urine at pH > 6.5, high uric acid concentration when ammonium is present serves as a cation [569-571].

4.7.3.Specific treatment

General preventive measures are recommended for fluid intake and diet. Hyperuricosuric stone formers benefit from purine reduction in their daily diet. Figure 4.5 describes pharmacological treatment [22,482,565-577]. For uric acid stones, allopurinol may change the stone composition distribution in patients with gout to a pattern similar to that in stone formers without gout [578].

Figure 4.5: Diagnostic and therapeutic algorithm for uric acid- and ammonium urate stones

1 d: day.
2 tid: three times a day.
3 A higher pH may lead to calcium phosphate stone formation.
4 In patients with high uric acid excretion, allopurinol may be helpful.

4.7.4.Summary of evidence and guidelines for the management of uric acid- and ammonium urate stones

Summary of evidence	LE
Potassium citrate can be beneficial to alkalinise the urine in urate stone formers.	3
Allopurinol can be beneficial in hyperuricosuric urate stone formers.	1b

Recommendations	Strength rating
Prescribe potassium citrate to alkalinise the urine in urate stone formers.	Strong
Prescribe allopurinol in hyperuricosuric urate stone formers.	Strong

4.8.Struvite and infection stones

All infection-stone formers are deemed at high risk of recurrence. Struvite stones represent 2-15% of the stones sent for analysis. Stones that contain struvite may originate de novo or grow on pre-existing stones, which are infected with urea-splitting bacteria [579]. There are several factors predisposing patients to struvite stone formation (Table 4.9) [580].

4.8.1.Diagnosis

Blood analysis requires measurement of creatinine, and urinalysis requires repeat urine pH measurements and urine culture.

Interpretation

Infection stones contain the following minerals: struvite and/or carbonate apatite and/or ammonium urate. Urine culture typically provides evidence for urease-producing bacteria, which increase ammonia ions and develop alkaline urine (Table 4.10). Carbonate apatite starts to crystallise at a urine pH level of 6.8. Struvite only precipitates at pH > 7.2 [581,582]. Proteus mirabilis accounts for more than half of all urease-positive
UTIs [583,584].

4.8.2.Specific treatment

General preventive measures are recommended for fluid intake and diet. Specific measures include complete surgical stone removal [580], short- or long-term antibiotic treatment [585], urinary acidification using methionine [534] or ammonium chloride [586], and advice to restrict intake of urease [587,588]. For severe infections, acetohydroxamic acid may be an option [587,588] (Figure 4.6); however, it is not licensed/available in all European countries.

Eradication of infection after complete stone removal is desirable. The evidence regarding the duration of post-operative antibiotic administration is inconclusive.

4.8.3.Summary of evidence and guidelines for the management of infection stones

Summary of evidence	LE
Removing the stone material as completely as possible with surgery can reduce ongoing infection.	3-4
Antibiotics are beneficial after complete stone removal.	3
Ammonium chloride, 1 g, two or three times daily, can ensure urinary acidification to prevent recurrent infection.	3
Methionine, 200-500 mg, one to three times daily, can be used as an alternative to ammonium chloride, to ensure urinary acidification	3
Urease inhibitors in case of severe infection are occasionally used (if licensed).	1b

Recommendations	Strength rating
Surgically remove the stone material as completely as possible.	Strong
Prescribe antibiotics in case of persistent bacteriuria.	Strong
Prescribe ammonium chloride, 1 g, two or three times daily to ensure urinary acidification.	Weak
Prescribe methionine, 200-500 mg, one to three times daily, as an alternative, to ensure urinary acidification.	Weak

Table 4.9: Factors predisposing to struvite stone formation

Neurogenic bladder

Spinal cord injury/paralysis

Continent urinary diversion

Ileal conduit

Foreign body

Stone disease

Indwelling urinary catheter

Urethral stricture

Benign prostatic hyperplasia

Bladder diverticulum

Cystocele

Calyceal diverticulum

UPJ obstruction

Table 4.10: Most important species of urease-producing bacteria

Obligate urease-producing bacteria (> 98%)

Proteus spp.

Providencia rettgeri

Morganella morganii

Corynebacterium urealyticum

Ureaplasma urealyticum

Facultative urease-producing bacteria

Enterobacter gergoviae

Klebsiella spp.

Providencia stuartii

Serratia marcescens

Staphylococcus spp.

CAUTION: 0-5% of Escherichia coli, Enterococcus spp. and Pseudomonas aeruginosa strains may produce urease.

Figure 4.6: Diagnostic and therapeutic algorithm for infection stones

1 Discussed with uric acid stones.
2 Acetohydroxamic acid.
* When nationally available.
bid = twice a day; tid = three times a day.

4.9.Cystine stones

Cystine stones account for 1-2% of all urinary stones in adults and 6-8% of the stones reported in paediatric studies [32,589]. All cystine stone formers are deemed at high risk of recurrence.

4.9.1.Diagnosis

Blood analysis includes measurement of creatinine, and urinalysis includes measurement of urine volume, pH profile, specific weight, and cystine.

Interpretation

Cystine is poorly soluble in urine and crystallises spontaneously within the physiological urinary pH range.
Cystine solubility depends strongly on urine pH: at pH 6.0, the limit of solubility is 1.33 mmol/L.
Routine analysis of cystine is not suitable for therapeutic monitoring.
Regardless of phenotype or genotype of the cystinuric patient, the clinical manifestations are the
same [590].
There is no role for genotyping patients in the routine management of cystinuria [591,592].
Reductive therapy targets the disulphide binding in the cysteine molecule. For therapy monitoring, it is essential to differentiate between cystine, cysteine and drug-cysteine complexes. Only high-performance liquid chromatography (HPLC)-based analysis differentiates between the different complexes formed by therapy.
Diagnosis is established by stone analysis. The typical hexagonal crystals are detectable in only 20-25% of urine specimens from patients with cystinuria [593].
The cyanide nitroprusside colorimetric qualitative test detects the presence of cystine at a threshold concentration of 75 mg/L, with a sensitivity of 72% and specificity of 95%. False-positive results in patients with Fanconi’s syndrome, homocystinuria, or those taking various drugs, including infection stones [594].
Quantitative 24-hour urinary cystine excretion confirms the diagnosis in the absence of stone analysis.
Levels above 30 mg/day are considered abnormal [595,596].

4.9.2.Specific treatment

General preventative measures for fluid intake and diet are recommended. A diet low in methionine may theoretically reduce urinary excretion of cystine; however, patients are unlikely to comply sufficiently with such a diet. A restricted intake of sodium is more easily achieved and is more effective in reducing urinary cystine. Patients are usually advised to avoid sodium consumption > 2 g/day [597]. A high level of diuresis is of fundamental importance, aiming for a 24-hour urine volume of > 3 L [598]. A considerable fluid intake evenly distributed throughout the day is necessary.

4.9.2.1.Pharmacological treatment of cystine stones

The main therapeutic option for avoiding cystine crystallisation is to maintain urine pH > 7.5, to improve cysteine solubility and ensure appropriate hydration with a minimum of 3.5 L/day in adults, or 1.5 L/m2 body surface area in children.

Free cystine concentration can be decreased by reductive substances, which act by splitting the disulphide binding of cysteine.

Tiopronin is currently the best choice for cystine reduction. However, side effects often lead to treatment termination, for example, when nephrotic syndrome develops, or poor compliance, especially with long-term use. After carefully considering the risk of early tachyphylaxis, putting into place a dose-escape phenomenon for long-term use, and recurrence risk, tiopronin is recommended at cystine levels > 3.0 mmol/day or in the case of recurring stone formation, notwithstanding other preventive measures.

Figure 4.7: Metabolic management of cystine stones

4.9.3.Summary of evidence and guidelines for the management of cystine stones

Summary of evidence	LE
Increasing fluid intake so that 24-hour urine volume exceeds 3 L is used to dilute the cystine.	3
Potassium citrate 3-10 mmol two or three times daily can be used to achieve pH > 7.5.	3
Tiopronin, 250-2,000 mg/day can be used to reduce stone formation in patients with cysteine excretion, > 3 mmol/day, or when other measures are insufficient.	3

Recommendations	Strength rating
Therapeutic measures
Urine dilution Advise patients to increase their fluid intake so that 24-hour urine volume exceeds 3 L.	Strong
Alkalinisation For patients with cystine excretion < 3 mmol/day, prescribe potassium citrate 3-10 mmol two or three times daily, to achieve pH > 7.5.	Strong
Complex formation with cystine For patients with cystine excretion, > 3 mmol/day, or when other measures are insufficient: prescribe in addition to other measures tiopronin, 250-2,000 mg/day.	Strong

4.10.2,8-Dihydroxyandenine stones and xanthine stones [22]

All 2,8-Dihydroxyadenine and xanthine stone formers are considered to be at high risk of recurrence. Both stone types are rare. Diagnosis and specific prevention are similar to those for uric acid stones.

4.10.1.2,8-Dihydroxyadenine stones

A genetically determined defect of adenine phosphoribosyl transferase causes high urinary excretion of poorly soluble 2,8-Dihydroxyadenine. High-dose allopurinol or febuxostat are important options, but should be given with regular monitoring.

4.10.2.Xanthine stones

Patients who form xanthine stones usually show decreased levels of serum uric acid. There is no available pharmacological intervention.

4.10.3.Fluid intake and diet

Recommendations for general preventive measures apply. Pharmacological intervention is difficult; therefore, high fluid intake ensures optimal specific weight levels of urine < 1.010. A purine-reduced diet decreases the risk of spontaneous crystallisation in urine.

4.11.Drug stones [57]

Drug stones are induced by pharmacological treatment [599] (Table 4.10). Two types exist:

stones formed by crystallised compounds of the drug;
stones formed due to unfavourable changes in urine composition under drug therapy.

Table 4.11: Compounds that cause drug stones

Active compounds crystallising in urine

Substances impairing urine composition

Allopurinol/oxypurinol

Amoxicillin/ampicillin

Ceftriaxone

Quinolones

Ephedrine

Indinavir

Magnesium trisilicate

Sulphonamides

Triamterene

Zonisamide

Acetazolamide

Allopurinol

Aluminium magnesium hydroxide

Ascorbic acid

Calcium

Furosemide

Laxatives

Methoxyflurane

Vitamin D

Topiramate

4.12.Matrix Stones

Pure matrix stones are extremely rare with less than 70 cases described in the literature. They are more prevalent in females. The main risk factors are recurrent UTIs, especially due to Proteous mirabilis or Escherichia coli, previous surgery for stone disease, chronic renal failure and haemodialysis. Complete endourological removal, frequently via the percutaneous approach, is critical. Given the rarity of matrix calculi a specific prophylactic regimen to minimise recurrence cannot be recommended. Eliminating infections and prophylactic use of antibiotics are most commonly proposed [600].

4.13.Unknown stone composition [16]

An accurate medical history is the first step towards identifying risk factors as summarised below (see Chapter 4.13.1).

Diagnostic imaging begins with US examination of both kidneys to establish whether the patient is stone free. Stone detection by US should be followed by KUB and unenhanced multislice CT in adults to differentiate between calcium-containing and non-calcium stones.

Blood analysis demonstrates severe metabolic and organic disorders, such as renal insufficiency, HPT or other hypercalcaemic states and hyperuricaemia. In children, hyperoxalaemia should additionally be screened for.

Urinalysis is performed routinely with a dipstick test as described above. Urine culture is required if there are signs of infection. Constant urine pH < 5.8 in the daily profile indicates acidic arrest, which may promote uric acid crystallisation. Persistent urine pH > 5.8 in the daily profile indicates RTA, if UTI is excluded.

Microscopy of urinary sediment can help to discover rare stone types, because crystals of 2,8-Dihydroxyadenine, cystine and xanthine are pathognomonic for the corresponding disease. In cases in which the presence of cystine is doubtful, a cyanide nitroprusside colorimetric qualitative test can be used to detect the presence of cystine in urine, with a sensitivity of 72% and specificity of 95%. False-positive results are possible in patients with Fanconi’s syndrome or homocystinuria, or in those taking various drugs, including ampicillin or sulfa-containing medication [594,601].

Following this programme, the most probable stone type can be assumed and specific patient evaluation can follow. However, if any expulsed stone material is available, it should be analysed by diagnostic confirmation or correction.

4.13.1.Guidelines for investigations for the assessment of patients with stones of unknown composition

Investigation	Rationale for investigation [16,22,57,64]	Strength rating
Take a medical history	• Stone history (former stone events, family history) • Dietary habits • Medication chart	Strong
Perform diagnostic imaging	• Ultrasound in the case of a suspected stone • Unenhanced helical computed tomography • Determination of Hounsfield units provides information about the possible stone composition	Strong
Perform a blood analysis	• Creatinine • Calcium (ionised calcium or total calcium + albumin) • Uric acid	Strong
Perform a urinalysis	• Urine pH profile (measurement after each voiding, minimum four times daily) • Dipstick test: leukocytes, erythrocytes, nitrite, protein, urine pH, specific weight • Urine cultures • Microscopy of urinary sediment (morning urine) • Cyanide nitroprusside test (cystine exclusion) Further examinations depend on the results of the investigations listed above.	Strong

5.REFERENCES

1.Skolarikos, A., et al. Metabolic evaluation and recurrence prevention for urinary stone patients: EAU guidelines. Eur Urol, 2015. 67: 750.

https://www.ncbi.nlm.nih.gov/pubmed/25454613

2.Turk, C., et al. EAU Guidelines on Diagnosis and Conservative Management of Urolithiasis. Eur Urol, 2016. 69: 468.

https://www.ncbi.nlm.nih.gov/pubmed/26318710

3.Turk, C., et al. EAU Guidelines on Interventional Treatment for Urolithiasis. Eur Urol, 2016. 69: 475.

https://www.ncbi.nlm.nih.gov/pubmed/26344917

4.Guyatt, G.H., et al. What is “quality of evidence” and why is it important to clinicians? Bmj, 2008. 336: 995.

https://www.ncbi.nlm.nih.gov/pubmed/18456631

5.Guyatt, G.H., et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ, 2008. 336: 924.

https://www.ncbi.nlm.nih.gov/pubmed/18436948

6.Phillips, B., et al. Oxford Centre for Evidence-based Medicine Levels of Evidence. Updated by Jeremy Howick March 2009.

https://www.cebm.net/2009/06/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/

7.Guyatt, G.H., et al. Going from evidence to recommendations. Bmj, 2008. 336: 1049.

https://www.ncbi.nlm.nih.gov/pubmed/18467413

8.Trinchieri A, et al., Epidemiology, In: Stone Disease, edited by Segura J, Conort P, Khoury S, Paris, France, ICUD, Distributed by Editions 21, 2003,

9.Stamatelou, K.K., et al. Time trends in reported prevalence of kidney stones in the United States: 1976-1994. Kidney Int, 2003. 63: 1817.

https://www.ncbi.nlm.nih.gov/pubmed/12675858

10.Hesse, A., et al. Study on the prevalence and incidence of urolithiasis in Germany comparing the years 1979 vs. 2000. Eur Urol, 2003. 44: 709.

https://www.ncbi.nlm.nih.gov/pubmed/14644124

11.Sanchez-Martin, F.M., et al. [Incidence and prevalence of published studies about urolithiasis in Spain. A review]. Actas Urol Esp, 2007. 31: 511.

https://www.ncbi.nlm.nih.gov/pubmed/17711170

12.Zhe, M., et al. Nephrolithiasis as a risk factor of chronic kidney disease: a meta-analysis of cohort studies with 4,770,691 participants. Urolithiasis, 2017. 45: 441.

https://www.ncbi.nlm.nih.gov/pubmed/27837248

13.Yasui, T., et al. 2082 Association of the loci 5q35.3, 7q14.3, and 13.q14.1 with urolithiasis: A case-control study in the Japanese population, involving genome-wide association study. J Urol, 2013. 189: e854.

https://www.jurology.com/article/S0022-5347(13)02777-8/abstract

14.Strohmaier, W.L. Course of calcium stone disease without treatment. What can we expect? Eur Urol, 2000. 37: 339.

https://www.ncbi.nlm.nih.gov/pubmed/10720863

15.Keoghane, S., et al. The natural history of untreated renal tract calculi. BJU Int, 2010. 105: 1627.

https://www.ncbi.nlm.nih.gov/pubmed/20438563

16.Straub, M., et al. Diagnosis and metaphylaxis of stone disease. Consensus concept of the National Working Committee on Stone Disease for the upcoming German Urolithiasis Guideline. World J Urol, 2005. 23: 309.

https://www.ncbi.nlm.nih.gov/pubmed/16315051

17.Pawar, A.S., et al. Incidence and characteristics of kidney stones in patients with horseshoe kidney: A systematic review and meta-analysis. Urol Ann, 2018. 10: 87.

https://www.ncbi.nlm.nih.gov/pubmed/29416282

18.Dissayabutra, T., et al. Urinary stone risk factors in the descendants of patients with kidney stone disease. Pediatr Nephrol, 2018. 33: 1173.

https://www.ncbi.nlm.nih.gov/pubmed/29594505

19.Hu, H., et al. Association between Circulating Vitamin D Level and Urolithiasis: A Systematic Review and Meta-Analysis. Nutrients, 2017. 9.

https://www.ncbi.nlm.nih.gov/pubmed/28335477

20.Geraghty, R.M., et al. Worldwide Impact of Warmer Seasons on the Incidence of Renal Colic and Kidney Stone Disease: Evidence from a Systematic Review of Literature. J Endourol, 2017. 31: 729.

https://www.ncbi.nlm.nih.gov/pubmed/28338351

21.Guo, Z.L., et al. Association between cadmium exposure and urolithiasis risk: A systematic review and meta-analysis. Medicine (Baltimore), 2018. 97: e9460.

https://www.ncbi.nlm.nih.gov/pubmed/29505519

22.Hesse, A.T., et al. Urinary Stones, Diagnosis, Treatment and Prevention of Recurrence. 3rd edition. 2009, Basel.

https://www.karger.com/Article/Pdf/232951

23.Basiri, A., et al. Familial relations and recurrence pattern in nephrolithiasis: new words about old subjects. Urol J, 2010. 7: 81.

https://www.ncbi.nlm.nih.gov/pubmed/20535692

24.Goldfarb, D.S., et al. A twin study of genetic and dietary influences on nephrolithiasis: a report from the Vietnam Era Twin (VET) Registry. Kidney Int, 2005. 67: 1053.

https://www.ncbi.nlm.nih.gov/pubmed/15698445

25.Asplin, J.R., et al. Hyperoxaluria in kidney stone formers treated with modern bariatric surgery.
J Urol, 2007. 177: 565.

https://www.ncbi.nlm.nih.gov/pubmed/17222634

26.Gonzalez, R.D., et al. Kidney stone risk following modern bariatric surgery. Curr Urol Rep, 2014.
15: 401.

https://www.ncbi.nlm.nih.gov/pubmed/24658828

27.Rendina, D., et al. Metabolic syndrome and nephrolithiasis: a systematic review and meta-analysis of the scientific evidence. J Nephrol, 2014. 27: 371.

https://www.ncbi.nlm.nih.gov/pubmed/24696310

28.Dell’Orto, V.G., et al. Metabolic disturbances and renal stone promotion on treatment with topiramate: a systematic review. Br J Clin Pharmacol, 2014. 77: 958.

https://www.ncbi.nlm.nih.gov/pubmed/24219102

29.Mufti, U.B., et al. Nephrolithiasis in autosomal dominant polycystic kidney disease. J Endourol, 2010. 24: 1557.

https://www.ncbi.nlm.nih.gov/pubmed/20818989

30.Chen, Y., et al. Current trend and risk factors for kidney stones in persons with spinal cord injury: a longitudinal study. Spinal Cord, 2000. 38: 346.

https://www.ncbi.nlm.nih.gov/pubmed/10889563

31.Hara, A., et al. Incidence of nephrolithiasis in relation to environmental exposure to lead and cadmium in a population study. Environ Res, 2016. 145: 1.

https://www.ncbi.nlm.nih.gov/pubmed/26613344

32.Leusmann, D.B., et al. Results of 5,035 stone analyses: a contribution to epidemiology of urinary stone disease. Scand J Urol Nephrol, 1990. 24: 205.

https://www.ncbi.nlm.nih.gov/pubmed/2237297

33.Leusmann, D.B. Whewellite, weddellite and company: where do all the strange names originate? BJU Int, 2000. 86: 411.

https://www.ncbi.nlm.nih.gov/pubmed/10971263

34.Kim, S.C., et al. Cystine calculi: correlation of CT-visible structure, CT number, and stone morphology with fragmentation by shock wave lithotripsy. Urol Res, 2007. 35: 319.

https://www.ncbi.nlm.nih.gov/pubmed/17965956

35.Wimpissinger, F., et al. The silence of the stones: asymptomatic ureteral calculi. J Urol, 2007.
178: 1341.

https://www.ncbi.nlm.nih.gov/pubmed/17706721

36.Ray, A.A., et al. Limitations to ultrasound in the detection and measurement of urinary tract calculi. Urology, 2010. 76: 295.

https://www.ncbi.nlm.nih.gov/pubmed/20206970

37.Smith-Bindman, R., et al. Ultrasonography versus computed tomography for suspected nephrolithiasis. N Engl J Med, 2014. 371: 1100.

https://www.ncbi.nlm.nih.gov/pubmed/25229916

38.Heidenreich, A., et al. Modern approach of diagnosis and management of acute flank pain: review of all imaging modalities. Eur Urol, 2002. 41: 351.

https://www.ncbi.nlm.nih.gov/pubmed/12074804

39.Kennish, S.J., et al. Is the KUB radiograph redundant for investigating acute ureteric colic in the non-contrast enhanced computed tomography era? Clin Radiol, 2008. 63: 1131.

https://www.ncbi.nlm.nih.gov/pubmed/18774360

40.Worster, A., et al. The accuracy of noncontrast helical computed tomography versus intravenous pyelography in the diagnosis of suspected acute urolithiasis: a meta-analysis. Ann Emerg Med, 2002. 40: 280.

https://www.ncbi.nlm.nih.gov/pubmed/12192351

41.Wu, D.S., et al. Indinavir urolithiasis. Curr Opin Urol, 2000. 10: 557.

https://www.ncbi.nlm.nih.gov/pubmed/11148725

42.El-Nahas, A.R., et al. A prospective multivariate analysis of factors predicting stone disintegration by extracorporeal shock wave lithotripsy: the value of high-resolution noncontrast computed tomography. Eur Urol, 2007. 51: 1688.

https://www.ncbi.nlm.nih.gov/pubmed/17161522

43.Patel, T., et al. Skin to stone distance is an independent predictor of stone-free status following shockwave lithotripsy. J Endourol, 2009. 23: 1383.

https://www.ncbi.nlm.nih.gov/pubmed/19694526

44.Zarse, C.A., et al. CT visible internal stone structure, but not Hounsfield unit value, of calcium oxalate monohydrate (COM) calculi predicts lithotripsy fragility in vitro. Urol Res, 2007. 35: 201.

https://www.ncbi.nlm.nih.gov/pubmed/17565491

45.Kluner, C., et al. Does ultra-low-dose CT with a radiation dose equivalent to that of KUB suffice to detect renal and ureteral calculi? J Comput Assist Tomogr, 2006. 30: 44.

https://www.ncbi.nlm.nih.gov/pubmed/16365571

46.Caoili, E.M., et al. Urinary tract abnormalities: initial experience with multi-detector row CT urography. Radiology, 2002. 222: 353.

https://www.ncbi.nlm.nih.gov/pubmed/11818599

47.Van Der Molen, A.J., et al. CT urography: definition, indications and techniques. A guideline for clinical practice. Eur Radiol, 2008. 18: 4.

https://www.ncbi.nlm.nih.gov/pubmed/17973110

48.Thomson, J.M., et al. Computed tomography versus intravenous urography in diagnosis of acute flank pain from urolithiasis: a randomized study comparing imaging costs and radiation dose. Australas Radiol, 2001. 45: 291.

https://www.ncbi.nlm.nih.gov/pubmed/11531751

49.Smith-Bindman, R., et al. Computed Tomography Radiation Dose in Patients With Suspected Urolithiasis. JAMA Intern Med, 2015. 175: 1413.

https://www.ncbi.nlm.nih.gov/pubmed/26121191

50.Rodger, F., et al. Diagnostic Accuracy of Low and Ultra-Low Dose CT for Identification of Urinary Tract Stones: A Systematic Review. Urol Int, 2018. 100: 375.

https://www.ncbi.nlm.nih.gov/pubmed/29649823

51.Xiang, H., et al. Systematic review and meta-analysis of the diagnostic accuracy of low-dose computed tomography of the kidneys, ureters and bladder for urolithiasis. J Med Imaging Radiat Oncol, 2017. 61: 582.

https://www.ncbi.nlm.nih.gov/pubmed/28139077

52.Poletti, P.A., et al. Low-dose versus standard-dose CT protocol in patients with clinically suspected renal colic. AJR Am J Roentgenol, 2007. 188: 927.

https://www.ncbi.nlm.nih.gov/pubmed/17377025

53.Zheng, X., et al. Dual-energy computed tomography for characterizing urinary calcified calculi and uric acid calculi: A meta-analysis. Eur J Radiol, 2016. 85: 1843.

https://www.ncbi.nlm.nih.gov/pubmed/27666626

54.Niemann, T., et al. Diagnostic performance of low-dose CT for the detection of urolithiasis: a meta-analysis. AJR Am J Roentgenol, 2008. 191: 396.

https://www.ncbi.nlm.nih.gov/pubmed/18647908

55.El-Wahab, O.A., et al. Multislice computed tomography vs. intravenous urography for planning supine percutaneous nephrolithotomy: A randomised clinical trial. Arab J Urol, 2014. 12: 162.

https://www.ncbi.nlm.nih.gov/pubmed/26019942

56.Thiruchelvam, N., et al. Planning percutaneous nephrolithotomy using multidetector computed tomography urography, multiplanar reconstruction and three-dimensional reformatting. BJU Int, 2005. 95: 1280.

https://www.ncbi.nlm.nih.gov/pubmed/15892817

57.Pearle, M.S., et al., Medical management of urolithiasis. 2nd International consultation on Stone Disease, Denstedt J., Khoury S. eds. 2008.

https://www.researchgate.net/publication/260000334_2nd_International_Consultation_on_Stone_Disease

58.Mandel, N., et al. Conversion of calcium oxalate to calcium phosphate with recurrent stone episodes. J Urol, 2003. 169: 2026.

https://www.ncbi.nlm.nih.gov/pubmed/12771710

59.Kourambas, J., et al. Role of stone analysis in metabolic evaluation and medical treatment of nephrolithiasis. J Endourol, 2001. 15: 181.

https://www.ncbi.nlm.nih.gov/pubmed/15843235

60.Hesse, A., et al. Quality control in urinary stone analysis: results of 44 ring trials (1980-2001).
Clin Chem Lab Med, 2005. 43: 298.

https://www.ncbi.nlm.nih.gov/pubmed/15843235

61.Sutor, D.J., et al. Identification standards for human urinary calculus components, using crystallographic methods. Br J Urol, 1968. 40: 22.

https://www.ncbi.nlm.nih.gov/pubmed/5642759

62.Abdel-Halim, R.E., et al. A review of urinary stone analysis techniques. Saudi Med J, 2006. 27: 1462.

https://www.ncbi.nlm.nih.gov/pubmed/17013464

63.Gilad, R., et al. Interpreting the results of chemical stone analysis in the era of modern stone analysis techniques. J Nephrol, 2017. 30: 135.

https://www.ncbi.nlm.nih.gov/pubmed/26956131

64.Bonkat, G., et al., EAU Guidelines on Urological Infections, in EAU Guidelines, Edn. published as the 32nd EAU Annual Meeting, London, 2017, European Association of Urology Guidelines Office: Arnhem, The Netherlands.

65.Somani, B.K., et al. Review on diagnosis and management of urolithiasis in pregnancy: an ESUT practical guide for urologists. World J Urol, 2017. 35: 1637.

https://www.ncbi.nlm.nih.gov/pubmed/28424869

66.Asrat, T., et al. Ultrasonographic detection of ureteral jets in normal pregnancy. Am J Obstet Gynecol, 1998. 178: 1194.

https://www.ncbi.nlm.nih.gov/pubmed/9662301

67.Swartz, M.A., et al. Admission for nephrolithiasis in pregnancy and risk of adverse birth outcomes. Obstet Gynecol, 2007. 109: 1099.

https://www.ncbi.nlm.nih.gov/pubmed/17470589

68.Patel, S.J., et al. Imaging the pregnant patient for nonobstetric conditions: algorithms and radiation dose considerations. Radiographics, 2007. 27: 1705.

https://www.ncbi.nlm.nih.gov/pubmed/18025513

69.Roy, C., et al. Assessment of painful ureterohydronephrosis during pregnancy by MR urography.
Eur Radiol, 1996. 6: 334.

https://www.ncbi.nlm.nih.gov/pubmed/8798002

70.Juan, Y.S., et al. Management of symptomatic urolithiasis during pregnancy. Kaohsiung J Med Sci, 2007. 23: 241.

https://www.ncbi.nlm.nih.gov/pubmed/17525006

71.Masselli, G., et al. Stone disease in pregnancy: imaging-guided therapy. Insights Imaging, 2014.
5: 691.

https://www.ncbi.nlm.nih.gov/pubmed/25249333

72.Safety Guidelines for Magnetic Resonance Imaging Equipment in Clinical Use, MHRA, Editor. 2015, MHRA.

http://www.ismrm.org/smrt/files/con2033065.pdf

73.ACOG Committee Opinion No. 723: Guidelines for Diagnostic Imaging During Pregnancy and Lactation. Obstet Gynecol, 2017. 130: e210.

https://www.acog.org/-/media/Committee-Opinions/Committee-on-Obstetric-Practice/co723.pdf?dmc=1&ts=20171118T0801492910

74.AIUM-ACR-ACOG-SMFM-SRU Practice parameter for the performance of obstetric ultrasound examinations 2013, Examinations, 2013, AIUM.

http://www.aium.org/resources/guidelines/obstetric.pdf

75.F.D.A., Avoid Fetal “Keepsake” Images, Heartbeat Monitors. 2014.

https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm095508.htm

76.Sharp, C., et al., Diagnostic Medical Exposures: Advice on Exposure to Ionising Radiation during Pregnancy. 1998.

https://inis.iaea.org/search/search.aspx?orig_q=RN:31046372

77.Kanal, E., et al. ACR guidance document for safe MR practices: 2007. AJR Am J Roentgenol, 2007. 188: 1447.

https://www.ncbi.nlm.nih.gov/pubmed/17515363

78.White, W.M., et al. Predictive value of current imaging modalities for the detection of urolithiasis during pregnancy: a multicenter, longitudinal study. J Urol, 2013. 189: 931.

https://www.ncbi.nlm.nih.gov/pubmed/23017526

79.Sternberg, K., et al. Pediatric stone disease: an evolving experience. J Urol, 2005. 174: 1711.

https://www.ncbi.nlm.nih.gov/pubmed/16148688

80.Palmer, L.S. Pediatric urologic imaging. Urol Clin North Am, 2006. 33: 409.

https://www.ncbi.nlm.nih.gov/pubmed/16829274

81.Passerotti, C., et al. Ultrasound versus computerized tomography for evaluating urolithiasis. J Urol, 2009. 182: 1829.

https://www.ncbi.nlm.nih.gov/pubmed/19692054

82.Tasian, G.E., et al. Evaluation and medical management of kidney stones in children. J Urol, 2014. 192: 1329.

https://www.ncbi.nlm.nih.gov/pubmed/24960469

83.Riccabona, M., et al. Imaging recommendations in paediatric uroradiology. Minutes of the ESPR uroradiology task force session on childhood obstructive uropathy, high-grade fetal hydronephrosis, childhood haematuria, and urolithiasis in childhood. ESPR Annual Congress, Edinburgh, UK, June 2008. Pediatr Radiol, 2009. 39: 891.

https://www.ncbi.nlm.nih.gov/pubmed/19565235

84.Darge, K., et al. [Modern ultrasound technologies and their application in pediatric urinary tract imaging]. Radiologe, 2005. 45: 1101.

https://www.ncbi.nlm.nih.gov/pubmed/16086170

85.Pepe, P., et al. Functional evaluation of the urinary tract by color-Doppler ultrasonography (CDU) in 100 patients with renal colic. Eur J Radiol, 2005. 53: 131.

https://www.ncbi.nlm.nih.gov/pubmed/15607864

86.Oner, S., et al. Comparison of spiral CT and US in the evaluation of pediatric urolithiasis. JBR-BTR, 2004. 87: 219.

https://www.ncbi.nlm.nih.gov/pubmed/15587558

87.Palmer, J.S., et al. Diagnosis of pediatric urolithiasis: role of ultrasound and computerized tomography. J Urol, 2005. 174: 1413.

https://www.ncbi.nlm.nih.gov/pubmed/16145452

88.Riccabona, M., et al. Conventional imaging in paediatric uroradiology. Eur J Radiol, 2002. 43: 100.

https://www.ncbi.nlm.nih.gov/pubmed/12127207

89.Chateil, J.F., et al. [Practical measurement of radiation dose in pediatric radiology: use of the dose surface product in digital fluoroscopy and for neonatal chest radiographs]. J Radiol, 2004. 85: 619.

https://www.ncbi.nlm.nih.gov/pubmed/15205653

90.Stratton, K.L., et al. Implications of ionizing radiation in the pediatric urology patient. J Urol, 2010. 183: 2137.

https://www.ncbi.nlm.nih.gov/pubmed/20399463

91.Tamm, E.P., et al. Evaluation of the patient with flank pain and possible ureteral calculus. Radiology, 2003. 228: 319.

https://www.ncbi.nlm.nih.gov/pubmed/12819343

92.Cody, D.D., et al. Strategies for formulating appropriate MDCT techniques when imaging the chest, abdomen, and pelvis in pediatric patients. AJR Am J Roentgenol, 2004. 182: 849.

https://www.ncbi.nlm.nih.gov/pubmed/15039151

93.Leppert, A., et al. Impact of magnetic resonance urography on preoperative diagnostic workup in children affected by hydronephrosis: should IVU be replaced? J Pediatr Surg, 2002. 37: 1441.

https://www.ncbi.nlm.nih.gov/pubmed/12378450

94.Engeler, D.S., et al. The ideal analgesic treatment for acute renal colic--theory and practice. Scand J Urol Nephrol, 2008. 42: 137.

https://www.ncbi.nlm.nih.gov/pubmed/17899475

95.Shokeir, A.A., et al. Resistive index in renal colic: the effect of nonsteroidal anti-inflammatory drugs. BJU Int, 1999. 84: 249.

https://www.ncbi.nlm.nih.gov/pubmed/10468715

96.Pathan, S.A., et al. Delivering safe and effective analgesia for management of renal colic in the emergency department: a double-blind, multigroup, randomised controlled trial. Lancet, 2016.
387: 1999.

https://www.ncbi.nlm.nih.gov/pubmed/26993881

97.Pathan, S.A., et al. A Systematic Review and Meta-analysis Comparing the Efficacy of Nonsteroidal Anti-inflammatory Drugs, Opioids, and Paracetamol in the Treatment of Acute Renal Colic. Eur Urol, 2018. 73: 583.

https://www.ncbi.nlm.nih.gov/pubmed/29174580

98.Afshar, K., et al. Nonsteroidal anti-inflammatory drugs (NSAIDs) and non-opioids for acute renal colic. Cochrane Database Syst Rev, 2015: CD006027.

https://www.ncbi.nlm.nih.gov/pubmed/26120804

99.Krum, H., et al. Blood pressure and cardiovascular outcomes in patients taking nonsteroidal antiinflammatory drugs. Cardiovasc Ther, 2012. 30: 342.

https://www.ncbi.nlm.nih.gov/pubmed/21884017

100.Bhala, N., et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet, 2013. 382: 769.

https://www.ncbi.nlm.nih.gov/pubmed/23726390

101.Holdgate, A., et al. Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal colic. Cochrane Database Syst Rev, 2005: CD004137.

https://www.ncbi.nlm.nih.gov/pubmed/15846699

102.Holdgate, A., et al. Systematic review of the relative efficacy of non-steroidal anti-inflammatory drugs and opioids in the treatment of acute renal colic. BMJ, 2004. 328: 1401.

https://www.ncbi.nlm.nih.gov/pubmed/15178585

103.Seitz, C., et al. Medical therapy to facilitate the passage of stones: what is the evidence? Eur Urol, 2009. 56: 455.

https://www.ncbi.nlm.nih.gov/pubmed/19560860

104.Lee, A., et al. Effects of nonsteroidal anti-inflammatory drugs on postoperative renal function in adults with normal renal function. Cochrane Database Syst Rev, 2007: CD002765.

https://www.ncbi.nlm.nih.gov/pubmed/17443518

105.Hollingsworth, J.M., et al. Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis. BMJ, 2016. 355: i6112.

https://www.ncbi.nlm.nih.gov/pubmed/27908918

106.Guercio, S., et al. Randomized prospective trial comparing immediate versus delayed ureteroscopy for patients with ureteral calculi and normal renal function who present to the emergency department. J Endourol, 2011. 25: 1137.

https://www.ncbi.nlm.nih.gov/pubmed/21682597

107.Ramsey, S., et al. Evidence-based drainage of infected hydronephrosis secondary to ureteric calculi. J Endourol, 2010. 24: 185.

https://www.ncbi.nlm.nih.gov/pubmed/20063999

108.Lynch, M.F., et al. Percutaneous nephrostomy and ureteric stent insertion for acute renal deobstruction: Consensus based guidance. Brit J Med Surg Urol, 2008. 1: 120.

https://www.sciencedirect.com/science/article/pii/S1875974208000955

109.Pearle, M.S., et al. Optimal method of urgent decompression of the collecting system for obstruction and infection due to ureteral calculi. J Urol, 1998. 160: 1260.

https://www.ncbi.nlm.nih.gov/pubmed/9751331

110.Wang, C.J., et al. Percutaneous nephrostomy versus ureteroscopic management of sepsis associated with ureteral stone impaction: a randomized controlled trial. Urolithiasis, 2016. 44: 415.

https://www.ncbi.nlm.nih.gov/pubmed/26662171

111.Marien, T., et al. Antimicrobial resistance patterns in cases of obstructive pyelonephritis secondary to stones. Urology, 2015. 85: 64.

https://www.ncbi.nlm.nih.gov/pubmed/25530365

112.Dellabella, M., et al. Randomized trial of the efficacy of tamsulosin, nifedipine and phloroglucinol in medical expulsive therapy for distal ureteral calculi. J Urol, 2005. 174: 167.

https://www.ncbi.nlm.nih.gov/pubmed/15947613

113.Borghi, L., et al. Nifedipine and methylprednisolone in facilitating ureteral stone passage:
a randomized, double-blind, placebo-controlled study. J Urol, 1994. 152: 1095.

https://www.ncbi.nlm.nih.gov/pubmed/8072071

114.Porpiglia, F., et al. Effectiveness of nifedipine and deflazacort in the management of distal ureter stones. Urology, 2000. 56: 579.

https://www.ncbi.nlm.nih.gov/pubmed/11018608

115.Dellabella, M., et al. Medical-expulsive therapy for distal ureterolithiasis: randomized prospective study on role of corticosteroids used in combination with tamsulosin-simplified treatment regimen and health-related quality of life. Urology, 2005. 66: 712.

https://www.ncbi.nlm.nih.gov/pubmed/16230122

116.Campschroer, T., et al. Alpha-blockers as medical expulsive therapy for ureteral stones. Cochrane Database Syst Rev, 2018. 4: CD008509.

https://www.ncbi.nlm.nih.gov/pubmed/24691989

117.Bai, Y., et al. Tadalafil Facilitates the Distal Ureteral Stone Expulsion: A Meta-Analysis. J Endourol, 2017. 31: 557.

https://www.ncbi.nlm.nih.gov/pubmed/28384011

118.Porpiglia, F., et al. Corticosteroids and tamsulosin in the medical expulsive therapy for symptomatic distal ureter stones: single drug or association? Eur Urol, 2006. 50: 339.

https://www.ncbi.nlm.nih.gov/pubmed/16574310

119.Yilmaz, E., et al. The comparison and efficacy of 3 different alpha1-adrenergic blockers for distal ureteral stones. J Urol, 2005. 173: 2010.

https://www.ncbi.nlm.nih.gov/pubmed/15879806

120.Wang, H., et al. Comparative efficacy of tamsulosin versus nifedipine for distal ureteral calculi:
a meta-analysis. Drug Des Devel Ther, 2016. 10: 1257.

https://www.ncbi.nlm.nih.gov/pubmed/27099471

121.Liu, X.J., et al. Role of silodosin as medical expulsive therapy in ureteral calculi: a meta-analysis of randomized controlled trials. Urolithiasis, 2017.

https://www.ncbi.nlm.nih.gov/pubmed/28365782

122.Pickard, R., et al. Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial. Lancet, 2015. 386: 341.

https://www.ncbi.nlm.nih.gov/pubmed/25998582

123.Furyk, J.S., et al. Distal Ureteric Stones and Tamsulosin: A Double-Blind, Placebo-Controlled, Randomized, Multicenter Trial. Ann Emerg Med, 2016. 67: 86.

https://www.ncbi.nlm.nih.gov/pubmed/26194935

124.Sur, R.L., et al. Silodosin to facilitate passage of ureteral stones: a multi-institutional, randomized, double-blinded, placebo-controlled trial. Eur Urol, 2015. 67: 959.

https://www.ncbi.nlm.nih.gov/pubmed/25465978

125.Turk, C., et al. Medical Expulsive Therapy for Ureterolithiasis: The EAU Recommendations in 2016. Eur Urol, 2016.

https://www.ncbi.nlm.nih.gov/pubmed/27506951

126.Kachrilas, S., et al. The current role of percutaneous chemolysis in the management of urolithiasis: review and results. Urolithiasis, 2013. 41: 323.

https://www.ncbi.nlm.nih.gov/pubmed/23743991

127.Bernardo, N.O., et al. Chemolysis of urinary calculi. Urol Clin North Am, 2000. 27: 355.

https://www.ncbi.nlm.nih.gov/pubmed/10778477

128.Tiselius, H.G., et al. Minimally invasive treatment of infection staghorn stones with shock wave lithotripsy and chemolysis. Scand J Urol Nephrol, 1999. 33: 286.

https://www.ncbi.nlm.nih.gov/pubmed/10572989

129.Rodman, J.S., et al. Dissolution of uric acid calculi. J Urol, 1984. 131: 1039.

https://www.ncbi.nlm.nih.gov/pubmed/6726897

130.Becker, G. Uric acid stones. Nephrology, 2007. 12: S21.

https://www.ncbi.nlm.nih.gov/pubmed/17316272

131.El-Gamal, O., et al. Role of combined use of potassium citrate and tamsulosin in the management of uric acid distal ureteral calculi. Urol Res, 2012. 40: 219.

https://www.ncbi.nlm.nih.gov/pubmed/21858663

132.Musa, A.A. Use of double-J stents prior to extracorporeal shock wave lithotripsy is not beneficial: results of a prospective randomized study. Int Urol Nephrol, 2008. 40: 19.

https://www.ncbi.nlm.nih.gov/pubmed/17394095

133.Shen, P., et al. Use of ureteral stent in extracorporeal shock wave lithotripsy for upper urinary calculi: a systematic review and meta-analysis. J Urol, 2011. 186: 1328.

https://www.ncbi.nlm.nih.gov/pubmed/21855945

134.Wang, H., et al. Meta-Analysis of Stenting versus Non-Stenting for the Treatment of Ureteral Stones. PLoS One, 2017. 12: e0167670.

https://www.ncbi.nlm.nih.gov/pubmed/28068364

135.Ghoneim, I.A., et al. Extracorporeal shock wave lithotripsy in impacted upper ureteral stones:
a prospective randomized comparison between stented and non-stented techniques. Urology, 2010. 75: 45.

https://www.ncbi.nlm.nih.gov/pubmed/19811806

136.Platonov, M.A., et al. Pacemakers, implantable cardioverter/defibrillators, and extracorporeal shockwave lithotripsy: evidence-based guidelines for the modern era. J Endourol, 2008. 22: 243.

https://www.ncbi.nlm.nih.gov/pubmed/18294028

137.Li, W.M., et al. Clinical predictors of stone fragmentation using slow-rate shock wave lithotripsy.
Urol Int, 2007. 79: 124.

https://www.ncbi.nlm.nih.gov/pubmed/17851280

138.Yilmaz, E., et al. Optimal frequency in extracorporeal shock wave lithotripsy: prospective randomized study. Urology, 2005. 66: 1160.

https://www.ncbi.nlm.nih.gov/pubmed/16360432

139.Pace, K.T., et al. Shock wave lithotripsy at 60 or 120 shocks per minute: a randomized, double-blind trial. J Urol, 2005. 174: 595.

https://www.ncbi.nlm.nih.gov/pubmed/16006908

140.Madbouly, K., et al. Slow versus fast shock wave lithotripsy rate for urolithiasis: a prospective randomized study. J Urol, 2005. 173: 127.

https://www.ncbi.nlm.nih.gov/pubmed/15592053

141.Semins, M.J., et al. The effect of shock wave rate on the outcome of shock wave lithotripsy: a meta-analysis. J Urol, 2008. 179: 194.

https://www.ncbi.nlm.nih.gov/pubmed/18001796

142.Li, K., et al. Optimal frequency of shock wave lithotripsy in urolithiasis treatment: a systematic review and meta-analysis of randomized controlled trials. J Urol, 2013. 190: 1260.

https://www.ncbi.nlm.nih.gov/pubmed/23538240

143.Nguyen, D.P., et al. Optimization of Extracorporeal Shock Wave Lithotripsy Delivery Rates Achieves Excellent Outcomes for Ureteral Stones: Results of a Prospective Randomized Trial. J Urol, 2015. 194: 418.

https://www.ncbi.nlm.nih.gov/pubmed/25661296

144.Pishchalnikov, Y.A., et al. Why stones break better at slow shockwave rates than at fast rates: in vitro study with a research electrohydraulic lithotripter. J Endourol, 2006. 20: 537.

https://www.ncbi.nlm.nih.gov/pubmed/16903810

145.Connors, B.A., et al. Extracorporeal shock wave lithotripsy at 60 shock waves/min reduces renal injury in a porcine model. BJU Int, 2009. 104: 1004.

https://www.ncbi.nlm.nih.gov/pubmed/19338532

146.Moon, K.B., et al. Optimal shock wave rate for shock wave lithotripsy in urolithiasis treatment:
a prospective randomized study. Korean J Urol, 2012. 53: 790.

https://www.ncbi.nlm.nih.gov/pubmed/23185672

147.Ng, C.F., et al. A prospective, randomized study of the clinical effects of shock wave delivery for unilateral kidney stones: 60 versus 120 shocks per minute. J Urol, 2012. 188: 837.

https://www.ncbi.nlm.nih.gov/pubmed/22819406

148.Kang, D.H., et al. Comparison of High, Intermediate, and Low Frequency Shock Wave Lithotripsy for Urinary Tract Stone Disease: Systematic Review and Network Meta-Analysis. PLoS One, 2016. 11: e0158661.

https://www.ncbi.nlm.nih.gov/pubmed/27387279

149.Lopez-Acon, J.D., et al. Analysis of the Efficacy and Safety of Increasing the Energy Dose Applied Per Session by Increasing the Number of Shock Waves in Extracorporeal Lithotripsy: A Prospective and Comparative Study. J Endourol, 2017. 31: 1289.

https://www.ncbi.nlm.nih.gov/pubmed/29048206

150.Connors, B.A., et al. Effect of initial shock wave voltage on shock wave lithotripsy-induced lesion size during step-wise voltage ramping. BJU Int, 2009. 103: 104.

https://www.ncbi.nlm.nih.gov/pubmed/18680494

151.Handa, R.K., et al. Optimising an escalating shockwave amplitude treatment strategy to protect the kidney from injury during shockwave lithotripsy. BJU Int, 2012. 110: E1041.

https://www.ncbi.nlm.nih.gov/pubmed/22612388

152.Skuginna, V., et al. Does Stepwise Voltage Ramping Protect the Kidney from Injury During Extracorporeal Shockwave Lithotripsy? Results of a Prospective Randomized Trial. Eur Urol, 2016. 69: 267.

https://www.ncbi.nlm.nih.gov/pubmed/26119561

153.Maloney, M.E., et al. Progressive increase of lithotripter output produces better in-vivo stone comminution. J Endourol, 2006. 20: 603.

https://www.ncbi.nlm.nih.gov/pubmed/16999607

154.Demirci, D., et al. Comparison of conventional and step-wise shockwave lithotripsy in management of urinary calculi. J Endourol, 2007. 21: 1407.

https://www.ncbi.nlm.nih.gov/pubmed/18044996

155.Honey, R.J., et al. Shock wave lithotripsy: a randomized, double-blind trial to compare immediate versus delayed voltage escalation. Urology, 2010. 75: 38.

https://www.ncbi.nlm.nih.gov/pubmed/19896176

156.Pishchalnikov, Y.A., et al. Air pockets trapped during routine coupling in dry head lithotripsy can significantly decrease the delivery of shock wave energy. J Urol, 2006. 176: 2706.

https://www.ncbi.nlm.nih.gov/pubmed/17085200

157.Jain, A., et al. Effect of air bubbles in the coupling medium on efficacy of extracorporeal shock wave lithotripsy. Eur Urol, 2007. 51: 1680.

https://www.ncbi.nlm.nih.gov/pubmed/17112655

158.Van Besien, J., et al. Ultrasonography Is Not Inferior to Fluoroscopy to Guide Extracorporeal Shock Waves during Treatment of Renal and Upper Ureteric Calculi: A Randomized Prospective Study. Biomed Res Int, 2017. 2017: 7802672.

https://www.ncbi.nlm.nih.gov/pubmed/28589147

159.Eichel, L., et al. Operator experience and adequate anesthesia improve treatment outcome with third-generation lithotripters. J Endourol, 2001. 15: 671.

https://www.ncbi.nlm.nih.gov/pubmed/11697394

160.Sorensen, C., et al. Comparison of intravenous sedation versus general anesthesia on the efficacy of the Doli 50 lithotriptor. J Urol, 2002. 168: 35.

https://www.ncbi.nlm.nih.gov/pubmed/12050487

161.Cleveland, R.O., et al. Effect of stone motion on in vitro comminution efficiency of Storz Modulith SLX. J Endourol, 2004. 18: 629.

https://www.ncbi.nlm.nih.gov/pubmed/15597649

162.Aboumarzouk, O.M., et al. Analgesia for patients undergoing shockwave lithotripsy for urinary stones - a systematic review and meta-analysis. Int Braz J Urol, 2017. 43: 394.

https://www.ncbi.nlm.nih.gov/pubmed/28338301

163.Honey, R.J., et al. A prospective study examining the incidence of bacteriuria and urinary tract infection after shock wave lithotripsy with targeted antibiotic prophylaxis. J Urol, 2013. 189: 2112.

https://www.ncbi.nlm.nih.gov/pubmed/23276509

164.Lu, Y., et al. Antibiotic prophylaxis for shock wave lithotripsy in patients with sterile urine before treatment may be unnecessary: a systematic review and meta-analysis. J Urol, 2012. 188: 441.

https://www.ncbi.nlm.nih.gov/pubmed/22704118

165.Chen, K., et al. The Efficacy and Safety of Tamsulosin Combined with Extracorporeal Shockwave Lithotripsy for Urolithiasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Endourol, 2015. 29: 1166.

https://www.ncbi.nlm.nih.gov/pubmed/25915454

166.Naja, V., et al. Tamsulosin facilitates earlier clearance of stone fragments and reduces pain after shockwave lithotripsy for renal calculi: results from an open-label randomized study. Urology, 2008. 72: 1006.

https://www.ncbi.nlm.nih.gov/pubmed/18799202

167.Zhu, Y., et al. alpha-Blockers to assist stone clearance after extracorporeal shock wave lithotripsy:
a meta-analysis. BJU Int, 2010. 106: 256.

https://www.ncbi.nlm.nih.gov/pubmed/19889063

168.Zheng, S., et al. Tamsulosin as adjunctive treatment after shockwave lithotripsy in patients with upper urinary tract stones: a systematic review and meta-analysis. Scand J Urol Nephrol, 2010.
44: 425.

https://www.ncbi.nlm.nih.gov/pubmed/21080841

169.Schuler, T.D., et al. Medical expulsive therapy as an adjunct to improve shockwave lithotripsy outcomes: a systematic review and meta-analysis. J Endourol, 2009. 23: 387.

https://www.ncbi.nlm.nih.gov/pubmed/19245302

170.Li, M., et al. Adjunctive medical therapy with alpha-blocker after extracorporeal shock wave lithotripsy of renal and ureteral stones: a meta-analysis. PLoS One, 2015. 10: e0122497.

https://www.ncbi.nlm.nih.gov/pubmed/25860144

171.Skolarikos, A., et al. The Efficacy of Medical Expulsive Therapy (MET) in Improving Stone-free Rate and Stone Expulsion Time, After Extracorporeal Shock Wave Lithotripsy (SWL) for Upper Urinary Stones: A Systematic Review and Meta-analysis. Urology, 2015. 86: 1057.

https://www.ncbi.nlm.nih.gov/pubmed/26383613

172.De Nunzio, C., et al. Tamsulosin or Silodosin Adjuvant Treatment Is Ineffective in Improving Shockwave Lithotripsy Outcome: A Short-Term Follow-Up Randomized, Placebo-Controlled Study. J Endourol, 2016. 30: 817.

https://www.ncbi.nlm.nih.gov/pubmed/27080916

173.Pearle, M.S., et al. Prospective, randomized trial comparing shock wave lithotripsy and ureteroscopy for lower pole caliceal calculi 1 cm or less. J Urol, 2005. 173: 2005.

https://www.ncbi.nlm.nih.gov/pubmed/15879805

174.Lingeman, J.E., et al. Comparison of results and morbidity of percutaneous nephrostolithotomy and extracorporeal shock wave lithotripsy. J Urol, 1987. 138: 485.

https://www.ncbi.nlm.nih.gov/pubmed/3625845

175.Chen, C.S., et al. Subcapsular hematoma of spleen--a complication following extracorporeal shock wave lithotripsy for ureteral calculus. Changgeng Yi Xue Za Zhi, 1992. 15: 215.

https://www.ncbi.nlm.nih.gov/pubmed/1295657

176.Skolarikos, A., et al. Extracorporeal shock wave lithotripsy 25 years later: complications and their prevention. Eur Urol, 2006. 50: 981.

https://www.ncbi.nlm.nih.gov/pubmed/16481097

177.Osman, M.M., et al. 5-year-follow-up of patients with clinically insignificant residual fragments after extracorporeal shockwave lithotripsy. Eur Urol, 2005. 47: 860.

https://www.ncbi.nlm.nih.gov/pubmed/15925084

178.Tan, Y.M., et al. Clinical experience and results of ESWL treatment for 3,093 urinary calculi with the Storz Modulith SL 20 lithotripter at the Singapore general hospital. Scand J Urol Nephrol, 2002. 36: 363.

https://www.ncbi.nlm.nih.gov/pubmed/12487741

179.Muller-Mattheis, V.G., et al. Bacteremia during extracorporeal shock wave lithotripsy of renal calculi. J Urol, 1991. 146: 733.

https://www.ncbi.nlm.nih.gov/pubmed/1875482

180.Dhar, N.B., et al. A multivariate analysis of risk factors associated with subcapsular hematoma formation following electromagnetic shock wave lithotripsy. J Urol, 2004. 172: 2271.

https://www.ncbi.nlm.nih.gov/pubmed/15538247

181.Zanetti, G., et al. Cardiac dysrhythmias induced by extracorporeal shockwave lithotripsy.
J Endourol, 1999. 13: 409.

https://www.ncbi.nlm.nih.gov/pubmed/10479005

182.Rodrigues Netto, N., Jr., et al. Small-bowel perforation after shockwave lithotripsy. J Endourol, 2003. 17: 719.

https://www.ncbi.nlm.nih.gov/pubmed/14642028

183.Holmberg, G., et al. Perforation of the bowel during SWL in prone position. J Endourol, 1997.
11: 313.

https://www.ncbi.nlm.nih.gov/pubmed/9355944

184.Maker, V., et al. Gastrointestinal injury secondary to extracorporeal shock wave lithotripsy: a review of the literature since its inception. J Am Coll Surg, 2004. 198: 128.

https://www.ncbi.nlm.nih.gov/pubmed/14698320

185.Kim, T.B., et al. Life-threatening complication after extracorporeal shock wave lithotripsy for a renal stone: a hepatic subcapsular hematoma. Korean J Urol, 2010. 51: 212.

https://www.ncbi.nlm.nih.gov/pubmed/20414400

186.Ng, C.F., et al. Hepatic haematoma after shockwave lithotripsy for renal stones. Urol Res, 2012.
40: 785.

https://www.ncbi.nlm.nih.gov/pubmed/22782117

187.Ather, M.H., et al. Does ureteral stenting prior to shock wave lithotripsy influence the need for intervention in steinstrasse and related complications? Urol Int, 2009. 83: 222.

https://www.ncbi.nlm.nih.gov/pubmed/19752621

188.Madbouly, K., et al. Risk factors for the formation of a steinstrasse after extracorporeal shock wave lithotripsy: a statistical model. J Urol, 2002. 167: 1239.

https://www.ncbi.nlm.nih.gov/pubmed/11832705

189.Sayed, M.A., et al. Steinstrasse after extracorporeal shockwave lithotripsy: aetiology, prevention and management. BJU Int, 2001. 88: 675.

https://www.ncbi.nlm.nih.gov/pubmed/11890235

190.Preminger, G.M., et al. 2007 Guideline for the management of ureteral calculi. Eur Urol, 2007.
52: 1610.

https://www.ncbi.nlm.nih.gov/pubmed/17993340

191.Lingeman, J.E., et al. Blood pressure changes following extracorporeal shock wave lithotripsy and other forms of treatment for nephrolithiasis. JAMA, 1990. 263: 1789.

https://www.ncbi.nlm.nih.gov/pubmed/2313851

192.Krambeck, A.E., et al. Diabetes mellitus and hypertension associated with shock wave lithotripsy of renal and proximal ureteral stones at 19 years of followup. J Urol, 2006. 175: 1742.

https://www.ncbi.nlm.nih.gov/pubmed/16600747

193.Eassa, W.A., et al. Prospective study of the long-term effects of shock wave lithotripsy on renal function and blood pressure. J Urol, 2008. 179: 964.

https://www.ncbi.nlm.nih.gov/pubmed/18207167

194.Yu, C., et al. A systematic review and meta-analysis of new onset hypertension after extracorporeal shock wave lithotripsy. Int Urol Nephrol, 2014. 46: 719.

https://www.ncbi.nlm.nih.gov/pubmed/24162890

195.Fankhauser, C.D., et al. Long-term Adverse Effects of Extracorporeal Shock-wave Lithotripsy for Nephrolithiasis and Ureterolithiasis: A Systematic Review. Urology, 2015. 85: 991.

https://www.ncbi.nlm.nih.gov/pubmed/25917723

196.Wendt-Nordahl, G., et al. Do new generation flexible ureterorenoscopes offer a higher treatment success than their predecessors? Urol Res, 2011. 39: 185.

https://www.ncbi.nlm.nih.gov/pubmed/21052986

197.Wang, Q., et al. Rigid ureteroscopic lithotripsy versus percutaneous nephrolithotomy for large proximal ureteral stones: A meta-analysis. PLoS One, 2017. 12: e0171478.

https://www.ncbi.nlm.nih.gov/pubmed/28182718

198.Wang, Y., et al. Comparison of the efficacy and safety of URSL, RPLU, and MPCNL for treatment of large upper impacted ureteral stones: a randomized controlled trial. BMC Urol, 2017. 17: 50.

https://www.ncbi.nlm.nih.gov/pubmed/28662708

199.Wu, T., et al. Ureteroscopic Lithotripsy versus Laparoscopic Ureterolithotomy or Percutaneous Nephrolithotomy in the Management of Large Proximal Ureteral Stones: A Systematic Review and Meta-Analysis. Urol Int, 2017. 99: 308.

https://www.ncbi.nlm.nih.gov/pubmed/28586770

200.Sun, X., et al. Treatment of large impacted proximal ureteral stones: randomized comparison of percutaneous antegrade ureterolithotripsy versus retrograde ureterolithotripsy. J Endourol, 2008.
22: 913.

https://www.ncbi.nlm.nih.gov/pubmed/18429682

201.el-Nahas, A.R., et al. Percutaneous treatment of large upper tract stones after urinary diversion. Urology, 2006. 68: 500.

https://www.ncbi.nlm.nih.gov/pubmed/16979745

202.Moufid, K., et al. Large impacted upper ureteral calculi: A comparative study between retrograde ureterolithotripsy and percutaneous antegrade ureterolithotripsy in the modified lateral position. Urol Ann, 2013. 5: 140.

https://www.ncbi.nlm.nih.gov/pubmed/24049373

203.Topaloglu, H., et al. A comparison of antegrade percutaneous and laparoscopic approaches in the treatment of proximal ureteral stones. Biomed Res Int, 2014. 2014: 691946.

https://www.ncbi.nlm.nih.gov/pubmed/25295266

204.El-Assmy, A., et al. Extracorporeal shock wave lithotripsy of upper urinary tract calculi in patients with cystectomy and urinary diversion. Urology, 2005. 66: 510.

https://www.ncbi.nlm.nih.gov/pubmed/16140067

205.Binbay, M., et al. Is there a difference in outcomes between digital and fiberoptic flexible ureterorenoscopy procedures? J Endourol, 2010. 24: 1929.

https://www.ncbi.nlm.nih.gov/pubmed/21043835

206.Geraghty, R., et al. Evidence for Ureterorenoscopy and Laser Fragmentation (URSL) for Large Renal Stones in the Modern Era. Curr Urol Rep, 2015. 16: 54.

https://www.ncbi.nlm.nih.gov/pubmed/26077357

207.Auge, B.K., et al. Ureteroscopic management of lower-pole renal calculi: technique of calculus displacement. J Endourol, 2001. 15: 835.

https://www.ncbi.nlm.nih.gov/pubmed/11724125

208.Cybulski, P.A., et al. Ureteroscopy: anesthetic considerations. Urol Clin North Am, 2004. 31: 43.

https://www.ncbi.nlm.nih.gov/pubmed/15040400

209.Dickstein, R.J., et al. Is a safety wire necessary during routine flexible ureteroscopy? J Endourol, 2010. 24: 1589.

https://www.ncbi.nlm.nih.gov/pubmed/20836719

210.Eandi, J.A., et al. Evaluation of the impact and need for use of a safety guidewire during ureteroscopy. J Endourol, 2008. 22: 1653.

https://www.ncbi.nlm.nih.gov/pubmed/18721045

211.Ulvik, O., et al. Ureteroscopy with and without safety guide wire: should the safety wire still be mandatory? J Endourol, 2013. 27: 1197.

https://www.ncbi.nlm.nih.gov/pubmed/23795760

212.Ambani, S.N., et al. Ureteral stents for impassable ureteroscopy. J Endourol, 2013. 27: 549.

https://www.ncbi.nlm.nih.gov/pubmed/23066997

213.Pace, K.T., et al. Same Session Bilateral Ureteroscopy for Multiple Stones: Results from the CROES URS Global Study. J Urol, 2017. 198: 130.

https://www.ncbi.nlm.nih.gov/pubmed/28163031

214.Ge, H., et al. Bilateral Same-Session Ureteroscopy for Treatment of Ureteral Calculi: A Systematic Review and Meta-Analysis. J Endourol, 2016. 30: 1169.

https://www.ncbi.nlm.nih.gov/pubmed/27626367

215.Stern, J.M., et al. Safety and efficacy of ureteral access sheaths. J Endourol, 2007. 21: 119.

https://www.ncbi.nlm.nih.gov/pubmed/17338606

216.L’Esperance J, O., et al. Effect of ureteral access sheath on stone-free rates in patients undergoing ureteroscopic management of renal calculi. Urology, 2005. 66: 252.

https://www.ncbi.nlm.nih.gov/pubmed/16040093

217.Traxer, O., et al. Prospective evaluation and classification of ureteral wall injuries resulting from insertion of a ureteral access sheath during retrograde intrarenal surgery. J Urol, 2013. 189: 580.

https://www.ncbi.nlm.nih.gov/pubmed/22982421

218.Aboumarzouk, O.M., et al. Flexible ureteroscopy and laser lithotripsy for stones >2 cm: a systematic review and meta-analysis. J Endourol, 2012. 26: 1257.

https://www.ncbi.nlm.nih.gov/pubmed/22642568

219.Traxer, O., et al. Differences in renal stone treatment and outcomes for patients treated either with or without the support of a ureteral access sheath: The Clinical Research Office of the Endourological Society Ureteroscopy Global Study. World J Urol, 2015. 33: 2137.

https://www.ncbi.nlm.nih.gov/pubmed/25971204

220.Santiago, J.E., et al. To Dust or Not To Dust: a Systematic Review of Ureteroscopic Laser Lithotripsy Techniques. Curr Urol Rep, 2017. 18: 32.

https://www.ncbi.nlm.nih.gov/pubmed/28271355

221.Bach, T., et al. Working tools in flexible ureterorenoscopy--influence on flow and deflection: what does matter? J Endourol, 2008. 22: 1639.

https://www.ncbi.nlm.nih.gov/pubmed/18620506

222.Leijte, J.A., et al. Holmium laser lithotripsy for ureteral calculi: predictive factors for complications and success. J Endourol, 2008. 22: 257.

https://www.ncbi.nlm.nih.gov/pubmed/18294030

223.Pierre, S., et al. Holmium laser for stone management. World J Urol, 2007. 25: 235.

https://www.ncbi.nlm.nih.gov/pubmed/17340157

224.Garg, S., et al. Ureteroscopic laser lithotripsy versus ballistic lithotripsy for treatment of ureteric stones: a prospective comparative study. Urol Int, 2009. 82: 341.

https://www.ncbi.nlm.nih.gov/pubmed/19440025

225.Binbay, M., et al. Evaluation of pneumatic versus holmium:YAG laser lithotripsy for impacted ureteral stones. Int Urol Nephrol, 2011. 43: 989.

https://www.ncbi.nlm.nih.gov/pubmed/21479563

226.Ahmed, M., et al. Systematic evaluation of ureteral occlusion devices: insertion, deployment, stone migration, and extraction. Urology, 2009. 73: 976.

https://www.ncbi.nlm.nih.gov/pubmed/19394493

227.John, T.T., et al. Adjunctive tamsulosin improves stone free rate after ureteroscopic lithotripsy of large renal and ureteric calculi: a prospective randomized study. Urology, 2010. 75: 1040.

https://www.ncbi.nlm.nih.gov/pubmed/19819530

228.Assimos, D., et al. Preoperative JJ stent placement in ureteric and renal stone treatment: results from the Clinical Research Office of Endourological Society (CROES) ureteroscopy (URS) Global Study. BJU Int, 2016. 117: 648.

https://www.ncbi.nlm.nih.gov/pubmed/26237735

229.Jessen, J.P., et al. International Collaboration in Endourology: Multicenter Evaluation of Prestenting for Ureterorenoscopy. J Endourol, 2016. 30: 268.

https://www.ncbi.nlm.nih.gov/pubmed/26582170

230.Song, T., et al. Meta-analysis of postoperatively stenting or not in patients underwent ureteroscopic lithotripsy. Urol Res, 2012. 40: 67.

https://www.ncbi.nlm.nih.gov/pubmed/21573923

231.Haleblian, G., et al. Ureteral stenting and urinary stone management: a systematic review. J Urol, 2008. 179: 424.

https://www.ncbi.nlm.nih.gov/pubmed/18076928

232.Nabi, G., et al. Outcomes of stenting after uncomplicated ureteroscopy: systematic review and meta-analysis. BMJ, 2007. 334: 572.

https://www.ncbi.nlm.nih.gov/pubmed/17311851

233.Seklehner, S., et al. A cost analysis of stenting in uncomplicated semirigid ureteroscopic stone removal. Int Urol Nephrol, 2017. 49: 753.

https://www.ncbi.nlm.nih.gov/pubmed/28197765

234.Moon, T.D. Ureteral stenting--an obsolete procedure? J Urol, 2002. 167: 1984.

https://www.ncbi.nlm.nih.gov/pubmed/11956423

235.Wang, C.J., et al. Effects of specific alpha-1A/1D blocker on lower urinary tract symptoms due to double-J stent: a prospectively randomized study. Urol Res, 2009. 37: 147.

https://www.ncbi.nlm.nih.gov/pubmed/19277623

236.Lamb, A.D., et al. Meta-analysis showing the beneficial effect of alpha-blockers on ureteric stent discomfort. BJU Int, 2011. 108: 1894.

https://www.ncbi.nlm.nih.gov/pubmed/21453351

237.Geavlete, P., et al. Complications of 2735 retrograde semirigid ureteroscopy procedures: a single-center experience. J Endourol, 2006. 20: 179.

https://www.ncbi.nlm.nih.gov/pubmed/16548724

238.Perez Castro, E., et al. Differences in ureteroscopic stone treatment and outcomes for distal, mid-, proximal, or multiple ureteral locations: the Clinical Research Office of the Endourological Society ureteroscopy global study. Eur Urol, 2014. 66: 102.

https://www.ncbi.nlm.nih.gov/pubmed/24507782

239.Ruhayel, Y., et al. Tract Sizes in Miniaturized Percutaneous Nephrolithotomy: A Systematic Review from the European Association of Urology Urolithiasis Guidelines Panel. Eur Urol, 2017. 72: 220.

https://www.ncbi.nlm.nih.gov/pubmed/28237786

240.Tikkinen, K.A.O., et al., EAU Guidelines on Thromboprophylaxis in Urological Surgery, in EAU Guidelines, Edn. published as the 32nd EAU Annual Meeting, London, EAU Guidelines Office, Editor. 2017, European Association of Urology Guidelines Office: Arnhem, The Netherlands.

https://uroweb.org/guideline/thromboprophylaxis/

241.Ganesamoni, R., et al. Prospective randomized controlled trial comparing laser lithotripsy with pneumatic lithotripsy in miniperc for renal calculi. J Endourol, 2013. 27: 1444.

https://www.ncbi.nlm.nih.gov/pubmed/24251428

242.Zhu, W., et al. A prospective and randomised trial comparing fluoroscopic, total ultrasonographic, and combined guidance for renal access in mini-percutaneous nephrolithotomy. BJU Int, 2017. 119: 612.

https://www.ncbi.nlm.nih.gov/pubmed/27862806

243.Wang, Y., et al. Prone versus modified supine position in percutaneous nephrolithotomy:
a prospective randomized study. Int J Med Sci, 2013. 10: 1518.

https://www.ncbi.nlm.nih.gov/pubmed/24046526

244.Mak, D.K., et al. What is better in percutaneous nephrolithotomy - Prone or supine? A systematic review. Arab J Urol, 2016. 14: 101.

https://www.ncbi.nlm.nih.gov/pubmed/27489736

245.Yuan, D., et al. Supine Versus Prone Position in Percutaneous Nephrolithotomy for Kidney Calculi:
A Meta-Analysis. J Endourol, 2016. 30: 754.

https://www.ncbi.nlm.nih.gov/pubmed/27072075

246.Cracco, C.M., et al. ECIRS (Endoscopic Combined Intrarenal Surgery) in the Galdakao-modified supine Valdivia position: a new life for percutaneous surgery? World J Urol, 2011. 29: 821.

https://www.ncbi.nlm.nih.gov/pubmed/22057344

247.Osman, M., et al. Percutaneous nephrolithotomy with ultrasonography-guided renal access: experience from over 300 cases. BJU Int, 2005. 96: 875.

https://www.ncbi.nlm.nih.gov/pubmed/16153221

248.Isac, W., et al. Endoscopic-guided versus fluoroscopic-guided renal access for percutaneous nephrolithotomy: a comparative analysis. Urology, 2013. 81: 251.

https://www.ncbi.nlm.nih.gov/pubmed/23374772

249.Falahatkar, S., et al. Complete supine PCNL: ultrasound vs. fluoroscopic guided: a randomized clinical trial. Int Braz J Urol, 2016. 42: 710.

https://www.ncbi.nlm.nih.gov/pubmed/27564281

250.Jessen, J.P., et al. Percutaneous nephrolithotomy under combined sonographic/radiologic guided puncture: results of a learning curve using the modified Clavien grading system. World J Urol, 2013. 31: 1599.

https://www.ncbi.nlm.nih.gov/pubmed/23283412

251.Wang, K., et al. Ultrasonographic versus Fluoroscopic Access for Percutaneous Nephrolithotomy:
A Meta-Analysis. Urol Int, 2015. 95: 15.

https://www.ncbi.nlm.nih.gov/pubmed/25678305

252.Lu, Y., et al. Randomized prospective trial of tubeless versus conventional minimally invasive percutaneous nephrolithotomy. World J Urol, 2013. 31: 1303.

https://www.ncbi.nlm.nih.gov/pubmed/22903789

253.Desai, M.R., et al. A prospective randomized comparison of type of nephrostomy drainage following percutaneous nephrostolithotomy: large bore versus small bore versus tubeless. J Urol, 2004. 172: 565.

https://www.ncbi.nlm.nih.gov/pubmed/15247731

254.Cormio, L., et al. Exit strategies following percutaneous nephrolithotomy (PCNL): a comparison of surgical outcomes in the Clinical Research Office of the Endourological Society (CROES) PCNL Global Study. World J Urol, 2013. 31: 1239.

https://www.ncbi.nlm.nih.gov/pubmed/22752586

255.Lee, J.Y., et al. Intraoperative and postoperative feasibility and safety of total tubeless, tubeless, small-bore tube, and standard percutaneous nephrolithotomy: a systematic review and network meta-analysis of 16 randomized controlled trials. BMC Urol, 2017. 17: 48.

https://www.ncbi.nlm.nih.gov/pubmed/28655317

256.Istanbulluoglu, M.O., et al. Effectiveness of totally tubeless percutaneous nephrolithotomy in selected patients: a prospective randomized study. Int Urol Nephrol, 2009. 41: 541.

https://www.ncbi.nlm.nih.gov/pubmed/19165617

257.Garofalo, M., et al. Tubeless procedure reduces hospitalization and pain after percutaneous nephrolithotomy: results of a multivariable analysis. Urolithiasis, 2013. 41: 347.

https://www.ncbi.nlm.nih.gov/pubmed/23632910

258.Gonen, M., et al. Tubeless and stentless percutaneous nephrolithotomy in patients requiring supracostal access. Urol Int, 2009. 82: 440.

https://www.ncbi.nlm.nih.gov/pubmed/19506412

259.Seitz, C., et al. Incidence, prevention, and management of complications following percutaneous nephrolitholapaxy. Eur Urol, 2012. 61: 146.

https://www.ncbi.nlm.nih.gov/pubmed/21978422

260.Zanetti, G., et al. Infections and urolithiasis: current clinical evidence in prophylaxis and antibiotic therapy. Arch Ital Urol Androl, 2008. 80: 5.

https://www.ncbi.nlm.nih.gov/pubmed/18533618

261.Gonen, M., et al. Factors affecting fever following percutaneous nephrolithotomy: a prospective clinical study. J Endourol, 2008. 22: 2135.

https://www.ncbi.nlm.nih.gov/pubmed/19506412

262.Wu, C., et al. Comparison of renal pelvic pressure and postoperative fever incidence between standard- and mini-tract percutaneous nephrolithotomy. Kaohsiung J Med Sci, 2017. 33: 36.

https://www.ncbi.nlm.nih.gov/pubmed/28088272

263.Mariappan, P., et al. Stone and pelvic urine culture and sensitivity are better than bladder urine as predictors of urosepsis following percutaneous nephrolithotomy: a prospective clinical study. J Urol, 2005. 173: 1610.

https://www.ncbi.nlm.nih.gov/pubmed/15821509

264.Lo, C.W., et al. Effectiveness of Prophylactic Antibiotics against Post-Ureteroscopic Lithotripsy Infections: Systematic Review and Meta-Analysis. Surg Infect (Larchmt), 2015. 16: 415.

https://www.ncbi.nlm.nih.gov/pubmed/26207401

265.Gravas, S., et al. Postoperative infection rates in low risk patients undergoing percutaneous nephrolithotomy with and without antibiotic prophylaxis: a matched case control study. J Urol, 2012. 188: 843.

https://www.ncbi.nlm.nih.gov/pubmed/22819398

266.Chew, B.H., et al. A Single Dose of Intraoperative Antibiotics Is Sufficient to Prevent Urinary Tract Infection During Ureteroscopy. J Endourol, 2016. 30: 63.

https://www.ncbi.nlm.nih.gov/pubmed/26413885

267.Klingler, H.C., et al. Stone treatment and coagulopathy. Eur Urol, 2003. 43: 75.

https://www.ncbi.nlm.nih.gov/pubmed/12507547

268.Kefer, J.C., et al. Safety and efficacy of percutaneous nephrostolithotomy in patients on anticoagulant therapy. J Urol, 2009. 181: 144.

https://www.ncbi.nlm.nih.gov/pubmed/19012931

269.Baron, T.H., et al. Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med, 2013. 368: 2113.

https://www.ncbi.nlm.nih.gov/pubmed/23718166

270.Naspro, R., et al. Antiplatelet therapy in patients with coronary stent undergoing urologic surgery: is it still no man’s land? Eur Urol, 2013. 64: 101.

https://www.ncbi.nlm.nih.gov/pubmed/23428067

271.Eberli, D., et al. Urological surgery and antiplatelet drugs after cardiac and cerebrovascular accidents. J Urol, 2010. 183: 2128.

https://www.ncbi.nlm.nih.gov/pubmed/20399452

272.Razvi, H., et al. Risk factors for perinephric hematoma formation after shockwave lithotripsy:
a matched case-control analysis. J Endourol, 2012. 26: 1478.

https://www.ncbi.nlm.nih.gov/pubmed/22712655

273.Rassweiler, J.J., et al. Treatment of renal stones by extracorporeal shockwave lithotripsy: an update. Eur Urol, 2001. 39: 187.

https://www.ncbi.nlm.nih.gov/pubmed/11223679

274.Fischer, C., et al. [Extracorporeal shock-wave lithotripsy induced ultrastructural changes to the renal parenchyma under aspirin use. Electron microscopic findings in the rat kidney]. Urologe A, 2007. 46: 150.

https://www.ncbi.nlm.nih.gov/pubmed/17221245

275.Becopoulos, T., et al. Extracorporeal lithotripsy in patients with hemophilia. Eur Urol, 1988. 14: 343.

https://www.ncbi.nlm.nih.gov/pubmed/3169076

276.Ishikawa, J., et al. Extracorporeal shock wave lithotripsy in von Willebrand’s disease. Int J Urol, 1996. 3: 58.

https://www.ncbi.nlm.nih.gov/pubmed/8646601

277.Zanetti, G., et al. Cardiac dysrhythmiastreated with antithrombotic agents. J Endourol, 2001. 15: 237.

https://www.ncbi.nlm.nih.gov/pubmed/11339387

278.Schnabel, M.J., et al. Incidence and risk factors of renal hematoma: a prospective study of 1,300 SWL treatments. Urolithiasis, 2014. 42: 247.

https://www.ncbi.nlm.nih.gov/pubmed/24419328

279.Schnabel, M.J., et al. Antiplatelet and anticoagulative medication during shockwave lithotripsy.
J Endourol, 2014. 28: 1034.

https://www.ncbi.nlm.nih.gov/pubmed/24851726

280.Aboumarzouk, O.M., et al. Flexible ureteroscopy and holmium:YAG laser lithotripsy for stone disease in patients with bleeding diathesis: a systematic review of the literature. Int Braz J Urol, 2012. 38: 298.

https://www.ncbi.nlm.nih.gov/pubmed/22765861

281.Elkoushy, M.A., et al. Ureteroscopy in patients with coagulopathies is associated with lower stone-free rate and increased risk of clinically significant hematuria. Int Braz J Urol, 2012. 38: 195.

https://www.ncbi.nlm.nih.gov/pubmed/22555043

282.Sharaf, A., et al. Ureteroscopy in Patients with Bleeding Diatheses, Anticoagulated, and on Anti-Platelet Agents: A Systematic Review and Meta-Analysis of the Literature. J Endourol, 2017.
31: 1217.

https://www.ncbi.nlm.nih.gov/pubmed/29048211

283.Sahin, C., et al. Transient cessation of antiplatelet medication before percutaneous stone surgery: does it have any safety concern on bleeding related problems? Urolithiasis, 2017. 45: 371.

https://www.ncbi.nlm.nih.gov/pubmed/9763079

284.Kuo, R.L., et al. Use of ureteroscopy and holmium:YAG laser in patients with bleeding diatheses. Urology, 1998. 52: 609.

https://www.ncbi.nlm.nih.gov/pubmed/9763079

285.Altay, B., et al. A review study to evaluate holmium:YAG laser lithotripsy with flexible ureteroscopy in patients on ongoing oral anticoagulant therapy. Lasers Med Sci, 2017. 32: 1615.

https://www.ncbi.nlm.nih.gov/pubmed/28733910

286.Gupta, A.D., et al. Coronary stent management in elective genitourinary surgery. BJU Int, 2012.
110: 480.

https://www.ncbi.nlm.nih.gov/pubmed/22192977

287.Delakas, D., et al. Independent predictors of failure of shockwave lithotripsy for ureteral stones employing a second-generation lithotripter. J Endourol, 2003. 17: 201.

https://www.ncbi.nlm.nih.gov/pubmed/12816580

288.Lee, J.Y., et al. Stone heterogeneity index as the standard deviation of Hounsfield units: A novel predictor for shock-wave lithotripsy outcomes in ureter calculi. Scientific Reports, 2016. 6: 23988.

https://www.ncbi.nlm.nih.gov/pubmed/27035621

289.Ohmori, K., et al. Effects of shock waves on the mouse fetus. J Urol, 1994. 151: 255.

https://www.ncbi.nlm.nih.gov/pubmed/8254823

290.Streem, S.B., et al. Extracorporeal shock wave lithotripsy in patients with bleeding diatheses. J Urol, 1990. 144: 1347.

https://www.ncbi.nlm.nih.gov/pubmed/2231922

291.Carey, S.W., et al. Extracorporeal shock wave lithotripsy for patients with calcified ipsilateral renal arterial or abdominal aortic aneurysms. J Urol, 1992. 148: 18.

https://www.ncbi.nlm.nih.gov/pubmed/1613866

292.Skolarikos, A., et al. The role for active monitoring in urinary stones: a systematic review. J Endourol, 2010. 24: 923.

https://www.ncbi.nlm.nih.gov/pubmed/20482232

293.Skolarikos, A., et al. Indications, prediction of success and methods to improve outcome of shock wave lithotripsy of renal and upper ureteral calculi. Arch Ital Urol Androl, 2010. 82: 56.

https://www.ncbi.nlm.nih.gov/pubmed/20593724

294.Cui, X., et al. Comparison between extracorporeal shock wave lithotripsy and ureteroscopic lithotripsy for treating large proximal ureteral stones: a meta-analysis. Urology, 2015. 85: 748.

https://www.ncbi.nlm.nih.gov/pubmed/25681251

295.Ishii, H., et al. Outcomes of Systematic Review of Ureteroscopy for Stone Disease in the Obese and Morbidly Obese Population. J Endourol, 2016. 30: 135.

https://www.ncbi.nlm.nih.gov/pubmed/26415049

296.Drake, T., et al. What are the Benefits and Harms of Ureteroscopy Compared with Shock-wave Lithotripsy in the Treatment of Upper Ureteral Stones? A Systematic Review. Eur Urol, 2017.
72: 772.

https://www.ncbi.nlm.nih.gov/pubmed/28456350

297.Inci, K., et al. Prospective long-term followup of patients with asymptomatic lower pole caliceal stones. J Urol, 2007. 177: 2189.

https://www.ncbi.nlm.nih.gov/pubmed/17509315

298.Brandt, B., et al. Painful caliceal calculi. The treatment of small nonobstructing caliceal calculi in patients with symptoms. Scand J Urol Nephrol, 1993. 27: 75.

https://www.ncbi.nlm.nih.gov/pubmed/8493473

299.Burgher, A., et al. Progression of nephrolithiasis: long-term outcomes with observation of asymptomatic calculi. J Endourol, 2004. 18: 534.

https://www.ncbi.nlm.nih.gov/pubmed/15333216

300.Hubner, W., et al. Treatment of caliceal calculi. Br J Urol, 1990. 66: 9.

https://www.ncbi.nlm.nih.gov/pubmed/2393803

301.Keeley, F.X., Jr., et al. Preliminary results of a randomized controlled trial of prophylactic shock wave lithotripsy for small asymptomatic renal calyceal stones. BJU Int, 2001. 87: 1.

https://www.ncbi.nlm.nih.gov/pubmed/11121982

302.Glowacki, L.S., et al. The natural history of asymptomatic urolithiasis. J Urol, 1992. 147: 319.

https://www.ncbi.nlm.nih.gov/pubmed/1732583

303.Collins, J.W., et al. Is there a role for prophylactic shock wave lithotripsy for asymptomatic calyceal stones? Curr Opin Urol, 2002. 12: 281.

https://www.ncbi.nlm.nih.gov/pubmed/12072647

304.Rebuck, D.A., et al. The natural history of renal stone fragments following ureteroscopy. Urology, 2011. 77: 564.

https://www.ncbi.nlm.nih.gov/pubmed/21109293

305.Andersson, L., et al. Small renal caliceal calculi as a cause of pain. J Urol, 1983. 130: 752.

https://www.ncbi.nlm.nih.gov/pubmed/6887409

306.Mee, S.L., et al. Small caliceal stones: is extracorporeal shock wave lithotripsy justified? J Urol, 1988. 139: 908.

https://www.ncbi.nlm.nih.gov/pubmed/3361660

307.Argyropoulos, A.N., et al. Evaluation of outcome following lithotripsy. Curr Opin Urol, 2010. 20: 154.

https://www.ncbi.nlm.nih.gov/pubmed/19898239

308.Srisubat, A., et al. Extracorporeal shock wave lithotripsy (ESWL) versus percutaneous nephrolithotomy (PCNL) or retrograde intrarenal surgery (RIRS) for kidney stones. Cochrane Database Syst Rev, 2014. 11: CD007044.

https://www.ncbi.nlm.nih.gov/pubmed/25418417

309.Sahinkanat, T., et al. Evaluation of the effects of relationships between main spatial lower pole calyceal anatomic factors on the success of shock-wave lithotripsy in patients with lower pole kidney stones. Urology, 2008. 71: 801.

https://www.ncbi.nlm.nih.gov/pubmed/18279941

310.Danuser, H., et al. Extracorporeal shock wave lithotripsy of lower calyx calculi: how much is treatment outcome influenced by the anatomy of the collecting system? Eur Urol, 2007. 52: 539.

https://www.ncbi.nlm.nih.gov/pubmed/17400366

311.Preminger, G.M. Management of lower pole renal calculi: shock wave lithotripsy versus percutaneous nephrolithotomy versus flexible ureteroscopy. Urol Res, 2006. 34: 108.

https://www.ncbi.nlm.nih.gov/pubmed/16463145

312.Zheng, C., et al. Extracorporeal shock wave lithotripsy versus retrograde intrarenal surgery for treatment for renal stones 1-2 cm: a meta-analysis. Urolithiasis, 2015. 43: 549.

https://www.ncbi.nlm.nih.gov/pubmed/26211003

313.Zheng, C., et al. Retrograde intrarenal surgery versus percutaneous nephrolithotomy for treatment of renal stones >2 cm: a meta-analysis. Urol Int, 2014. 93: 417.

https://www.ncbi.nlm.nih.gov/pubmed/25170589

314.Karakoyunlu, N., et al. A comparison of standard PCNL and staged retrograde FURS in pelvis stones over 2 cm in diameter: a prospective randomized study. Urolithiasis, 2015. 43: 283.

https://www.ncbi.nlm.nih.gov/pubmed/25295266

315.Donaldson, J.F., et al. Systematic review and meta-analysis of the clinical effectiveness of shock wave lithotripsy, retrograde intrarenal surgery, and percutaneous nephrolithotomy for lower-pole renal stones. Eur Urol, 2015. 67: 612.

https://www.ncbi.nlm.nih.gov/pubmed/25449204

316.Kumar, A., et al. A prospective, randomized comparison of shock wave lithotripsy, retrograde intrarenal surgery and miniperc for treatment of 1 to 2 cm radiolucent lower calyceal renal calculi:
a single center experience. J Urol, 2015. 193: 160.

https://www.ncbi.nlm.nih.gov/pubmed/25177768

317.Sener, N.C., et al. Prospective randomized trial comparing shock wave lithotripsy and flexible ureterorenoscopy for lower pole stones smaller than 1 cm. Urolithiasis, 2014. 42: 127.

https://www.ncbi.nlm.nih.gov/pubmed/24220692

318.Manikandan, R., et al. Do anatomic factors pose a significant risk in the formation of lower pole stones? Urology, 2007. 69: 620.

https://www.ncbi.nlm.nih.gov/pubmed/17445636

319.De, S., et al. Percutaneous nephrolithotomy versus retrograde intrarenal surgery: a systematic review and meta-analysis. Eur Urol, 2015. 67: 125.

https://www.ncbi.nlm.nih.gov/pubmed/25064687

320.Sener, N.C., et al. Asymptomatic lower pole small renal stones: shock wave lithotripsy, flexible ureteroscopy, or observation? A prospective randomized trial. Urology, 2015. 85: 33.

https://www.ncbi.nlm.nih.gov/pubmed/25440816

321.Kumar, A., et al. A Prospective Randomized Comparison Between Shock Wave Lithotripsy and Flexible Ureterorenoscopy for Lower Caliceal Stones </=2 cm: A Single-Center Experience.
J Endourol, 2015. 29: 575.

https://www.ncbi.nlm.nih.gov/pubmed/25203489

322.Mi, Y., et al. Flexible ureterorenoscopy (F-URS) with holmium laser versus extracorporeal shock wave lithotripsy (ESWL) for treatment of renal stone <2 cm: a meta-analysis. Urolithiasis, 2016.
44: 353.

https://www.ncbi.nlm.nih.gov/pubmed/26530230

323.Zhang, W., et al. Retrograde Intrarenal Surgery Versus Percutaneous Nephrolithotomy Versus Extracorporeal Shockwave Lithotripsy for Treatment of Lower Pole Renal Stones: A Meta-Analysis and Systematic Review. J Endourol, 2015. 29: 745.

https://www.ncbi.nlm.nih.gov/pubmed/25531986

324.Sumino, Y., et al. Predictors of lower pole renal stone clearance after extracorporeal shock wave lithotripsy. J Urol, 2002. 168: 1344.

https://www.ncbi.nlm.nih.gov/pubmed/12352389

325.Torricelli, F.C., et al. Impact of renal anatomy on shock wave lithotripsy outcomes for lower pole kidney stones: results of a prospective multifactorial analysis controlled by computerized tomography. J Urol, 2015. 193: 2002.

https://www.ncbi.nlm.nih.gov/pubmed/25524240

326.Gupta, N.P., et al. Infundibulopelvic anatomy and clearance of inferior caliceal calculi with shock wave lithotripsy. J Urol, 2000. 163: 24.

https://www.ncbi.nlm.nih.gov/pubmed/10604306

327.Abdelhamid, M., et al. A Prospective Evaluation of High-Resolution CT Parameters in Predicting Extracorporeal Shockwave Lithotripsy Success for Upper Urinary Tract Calculi. J Endourol, 2016. 30: 1227.

https://www.ncbi.nlm.nih.gov/pubmed/27597174

328.Madbouly, K., et al. Impact of lower pole renal anatomy on stone clearance after shock wave lithotripsy: fact or fiction? J Urol, 2001. 165: 1415.

https://www.ncbi.nlm.nih.gov/pubmed/11342888

329.Chiong, E., et al. Randomized controlled study of mechanical percussion, diuresis, and inversion therapy to assist passage of lower pole renal calculi after shock wave lithotripsy. Urology, 2005.
65: 1070.

https://www.ncbi.nlm.nih.gov/pubmed/15922429

330.Chan, L.H., et al. Primary SWL Is an Efficient and Cost-Effective Treatment for Lower Pole Renal Stones Between 10 and 20 mm in Size: A Large Single Center Study. J Endourol, 2017. 31: 510.

https://www.ncbi.nlm.nih.gov/pubmed/28355100

331.Hyams, E.S., et al. Flexible ureterorenoscopy and holmium laser lithotripsy for the management of renal stone burdens that measure 2 to 3 cm: a multi-institutional experience. J Endourol, 2010.
24: 1583.

https://www.ncbi.nlm.nih.gov/pubmed/20629566

332.Riley, J.M., et al. Retrograde ureteroscopy for renal stones larger than 2.5 cm. J Endourol, 2009.
23: 1395.

https://www.ncbi.nlm.nih.gov/pubmed/19694527

333.Akman, T., et al. Comparison of percutaneous nephrolithotomy and retrograde flexible nephrolithotripsy for the management of 2-4 cm stones: a matched-pair analysis. BJU Int, 2012. 109: 1384.

https://www.ncbi.nlm.nih.gov/pubmed/22093679

334.Assimos, D.G., et al. The role of open stone surgery since extracorporeal shock wave lithotripsy.
J Urol, 1989. 142: 263.

https://www.ncbi.nlm.nih.gov/pubmed/2746742

335.Segura, J.W. Current surgical approaches to nephrolithiasis. Endocrinol Metab Clin North Am, 1990. 19: 919.

https://www.ncbi.nlm.nih.gov/pubmed/2081519

336.Honeck, P., et al. Does open stone surgery still play a role in the treatment of urolithiasis? Data of a primary urolithiasis center. J Endourol, 2009. 23: 1209.

https://www.ncbi.nlm.nih.gov/pubmed/19538063

337.Bichler, K.H., et al. Indications for open stone removal of urinary calculi. Urol Int, 1997. 59: 102.

https://www.ncbi.nlm.nih.gov/pubmed/9392057

338.Paik, M.L., et al. Is there a role for open stone surgery? Urol Clin North Am, 2000. 27: 323.

https://www.ncbi.nlm.nih.gov/pubmed/10778474

339.Alivizatos, G., et al. Is there still a role for open surgery in the management of renal stones?
Curr Opin Urol, 2006. 16: 106.

https://www.ncbi.nlm.nih.gov/pubmed/16479213

340.Basiri, A., et al. Comparison of safety and efficacy of laparoscopic pyelolithotomy versus percutaneous nephrolithotomy in patients with renal pelvic stones: a randomized clinical trial. Urol J, 2014. 11: 1932.

https://www.ncbi.nlm.nih.gov/pubmed/25433470

341.Prakash, J., et al. Retroperitoneoscopic versus open mini-incision ureterolithotomy for upper- and mid-ureteric stones: a prospective randomized study. Urolithiasis, 2014. 42: 133.

https://www.ncbi.nlm.nih.gov/pubmed/24272062

342.Al-Hunayan, A., et al. Management of solitary renal pelvic stone: laparoscopic retroperitoneal pyelolithotomy versus percutaneous nephrolithotomy. J Endourol, 2011. 25: 975.

https://www.ncbi.nlm.nih.gov/pubmed/21612433

343.Skolarikos, A., et al. Laparoscopic urinary stone surgery: an updated evidence-based review.
Urol Res, 2010. 38: 337.

https://www.ncbi.nlm.nih.gov/pubmed/20396871

344.Giedelman, C., et al. Laparoscopic anatrophic nephrolithotomy: developments of the technique in the era of minimally invasive surgery. J Endourol, 2012. 26: 444.

https://www.ncbi.nlm.nih.gov/pubmed/22142215

345.Wang, X., et al. Laparoscopic pyelolithotomy compared to percutaneous nephrolithotomy as surgical management for large renal pelvic calculi: a meta-analysis. J Urol, 2013. 190: 888.

https://www.ncbi.nlm.nih.gov/pubmed/23454154

346.Singh, V., et al. Prospective randomized comparison of retroperitoneoscopic pyelolithotomy versus percutaneous nephrolithotomy for solitary large pelvic kidney stones. Urol Int, 2014. 92: 392.

https://www.ncbi.nlm.nih.gov/pubmed/24135482

347.Kumar, A., et al. A Prospective Randomized Comparison Between Laparoscopic Ureterolithotomy and Semirigid Ureteroscopy for Upper Ureteral Stones >2 cm: A Single-Center Experience.
J Endourol, 2015. 29: 1248.

https://www.ncbi.nlm.nih.gov/pubmed/25177768

348.Torricelli, F.C., et al. Semi-rigid ureteroscopic lithotripsy versus laparoscopic ureterolithotomy for large upper ureteral stones: a meta - analysis of randomized controlled trials. Int Braz J Urol, 2016. 42: 645.

https://www.ncbi.nlm.nih.gov/pubmed/27564273

349.Soltani M.H., et al. Stented Versus Stentless Laparoscopic Ureterolithotomy: A Systematic Review and Meta-Analysis. J Laparoen Adv Surg Tech, 2017. 27: 1269.

https://www.ncbi.nlm.nih.gov/pubmed/28631946

350.Coptcoat, M.J., et al. The steinstrasse: a legacy of extracorporeal lithotripsy? Eur Urol, 1988. 14: 93.

https://www.ncbi.nlm.nih.gov/pubmed/3360043

351.Lucio, J., 2nd, et al. Steinstrasse predictive factors and outcomes after extracorporeal shockwave lithotripsy. Int Braz J Urol, 2011. 37: 477.

https://www.ncbi.nlm.nih.gov/pubmed/21888699

352.Moursy, E., et al. Tamsulosin as an expulsive therapy for steinstrasse after extracorporeal shock wave lithotripsy: a randomized controlled study. Scand J Urol Nephrol, 2010. 44: 315.

https://www.ncbi.nlm.nih.gov/pubmed/20560802

353.Resim, S., et al. Role of tamsulosin in treatment of patients with steinstrasse developing after extracorporeal shock wave lithotripsy. Urology, 2005. 66: 945.

https://www.ncbi.nlm.nih.gov/pubmed/16286100

354.Rabbani, S.M. Treatment of steinstrasse by transureteral lithotripsy. Urol J, 2008. 5: 89.

https://www.ncbi.nlm.nih.gov/pubmed/18592460

355.Chew, B.H., et al. Natural History, Complications and Re-Intervention Rates of Asymptomatic Residual Stone Fragments after Ureteroscopy: a Report from the EDGE Research Consortium.
J Urol, 2016. 195: 982.

https://www.ncbi.nlm.nih.gov/pubmed/26585680

356.Candau, C., et al. Natural history of residual renal stone fragments after ESWL. Eur Urol, 2000.
37: 18.

https://www.ncbi.nlm.nih.gov/pubmed/10671779

357.Olvera-Posada, D., et al. Natural History of Residual Fragments After Percutaneous Nephrolithotomy: Evaluation of Factors Related to Clinical Events and Intervention. Urology, 2016. 97: 46.

https://www.ncbi.nlm.nih.gov/pubmed/27421779

358.Portis, A.J., et al. Confident intraoperative decision making during percutaneous nephrolithotomy: does this patient need a second look? Urology, 2008. 71: 218.

https://www.ncbi.nlm.nih.gov/pubmed/18308087

359.Tokas, T., et al. Uncovering the real outcomes of active renal stone treatment by utilizing non-contrast computer tomography: a systematic review of the current literature. World J Urol, 2017.
35: 897.

https://www.ncbi.nlm.nih.gov/pubmed/27738806

360.Omar, M., et al. Contemporary Imaging Practice Patterns Following Ureteroscopy for Stone Disease. J Endourol, 2015. 29: 1122.

https://www.ncbi.nlm.nih.gov/pubmed/25963170

361.Rippel, C.A., et al. Residual fragments following ureteroscopic lithotripsy: incidence and predictors on postoperative computerized tomography. J Urol, 2012. 188: 2246.

https://www.ncbi.nlm.nih.gov/pubmed/23083650

362.Gokce, M.I., et al. Comparison of imaging modalities for detection of residual fragments and prediction of stone related events following percutaneous nephrolitotomy. Int Braz J Urol, 2015.
41: 86.

https://www.ncbi.nlm.nih.gov/pubmed/25928513

363.Beck, E.M., et al. The fate of residual fragments after extracorporeal shock wave lithotripsy monotherapy of infection stones. J Urol, 1991. 145: 6.

https://www.ncbi.nlm.nih.gov/pubmed/1984100

364.El-Nahas, A.R., et al. Predictors of clinical significance of residual fragments after extracorporeal shockwave lithotripsy for renal stones. J Endourol, 2006. 20: 870.

https://www.ncbi.nlm.nih.gov/pubmed/17144853

365.Buchholz, N.P., et al. Minor residual fragments after extracorporeal shockwave lithotripsy: spontaneous clearance or risk factor for recurrent stone formation? J Endourol, 1997. 11: 227.

https://www.ncbi.nlm.nih.gov/pubmed/9376838

366.Tsai, Y.L., et al. Comparative study of conservative and surgical management for symptomatic moderate and severe hydronephrosis in pregnancy: a prospective randomized study. Acta Obstet Gynecol Scand, 2007. 86: 1047.

https://www.ncbi.nlm.nih.gov/pubmed/17712643

367.Mokhmalji, H., et al. Percutaneous nephrostomy versus ureteral stents for diversion of hydronephrosis caused by stones: a prospective, randomized clinical trial. J Urol, 2001. 165: 1088.

https://www.ncbi.nlm.nih.gov/pubmed/11257644

368.Ngai, H.Y., et al. Double-J ureteric stenting in pregnancy: A single-centre experience from Iraq.
Arab J Urol, 2013. 11: 148.

https://www.ncbi.nlm.nih.gov/pubmed/26558073

369.Ishii, H., et al. Current status of ureteroscopy for stone disease in pregnancy. Urolithiasis, 2014.
42: 1.

https://www.ncbi.nlm.nih.gov/pubmed/24374899

370.Teleb, M., et al. Definitive ureteroscopy and intracorporeal lithotripsy in treatment of ureteral calculi during pregnancy. Arab J Urol, 2014. 12: 299.

https://www.ncbi.nlm.nih.gov/pubmed/26019966

371.Toth, C., et al. Percutaneous nephrolithotomy in early pregnancy. Int Urol Nephrol, 2005. 37: 1.

https://www.ncbi.nlm.nih.gov/pubmed/16132747

372.Kato, H., et al. Continent urinary reservoir formation with transverse colon for patients with pelvic irradiation. Int J Urol, 2002. 9: 200.

https://www.ncbi.nlm.nih.gov/pubmed/12010313

373.Holmes, D.G., et al. Long-term complications related to the modified Indiana pouch. Urology, 2002. 60: 603.

https://www.ncbi.nlm.nih.gov/pubmed/12385916

374.Yang, W.J., et al. Long-term effects of ileal conduit urinary diversion on upper urinary tract in bladder cancer. Urology, 2006. 68: 324.

https://www.ncbi.nlm.nih.gov/pubmed/16904445

375.Assimos, D.G. Nephrolithiasis in patients with urinary diversion. J Urol, 1996. 155: 69.

https://www.ncbi.nlm.nih.gov/pubmed/7490901

376.Cohen, T.D., et al. Long-term incidence and risks for recurrent stones following contemporary management of upper tract calculi in patients with a urinary diversion. J Urol, 1996. 155: 62.

https://www.ncbi.nlm.nih.gov/pubmed/7490899

377.Deliveliotis, C., et al. Shockwave lithotripsy for urinary stones in patients with urinary diversion after radical cystectomy. J Endourol, 2002. 16: 717.

https://www.ncbi.nlm.nih.gov/pubmed/12542873

378.Stein, J.P., et al. Complications of the afferent antireflux valve mechanism in the Kock ileal reservoir. J Urol, 1996. 155: 1579.

https://www.ncbi.nlm.nih.gov/pubmed/8627827

379.Matlaga, B.R., et al. Computerized tomography guided access for percutaneous nephrostolithotomy. J Urol, 2003. 170: 45.

https://www.ncbi.nlm.nih.gov/pubmed/12796641

380.Hensle, T.W., et al. Preventing reservoir calculi after augmentation cystoplasty and continent urinary diversion: the influence of an irrigation protocol. BJU Int, 2004. 93: 585.

https://www.ncbi.nlm.nih.gov/pubmed/15008735

381.Raj, G.V., et al. The incidence of nephrolithiasis in patients with spinal neural tube defects. J Urol, 1999. 162: 1238.

https://www.ncbi.nlm.nih.gov/pubmed/10458475

382.Gros, D.A., et al. Urolithiasis in spina bifida. Eur J Pediatr Surg, 1998. 8 Suppl 1: 68.

https://www.ncbi.nlm.nih.gov/pubmed/9926338

383.Kondo, A., et al. [Urolithiasis in those patients with myelodysplasia]. Nihon Hinyokika Gakkai Zasshi, 2003. 94: 15.

https://www.ncbi.nlm.nih.gov/pubmed/12638200

384.Rendeli, C., et al. Latex sensitisation and allergy in children with myelomeningocele. Childs Nerv Syst, 2006. 22: 28.

https://www.ncbi.nlm.nih.gov/pubmed/15703967

385.Christman, M.S., et al. Morbidity and efficacy of ureteroscopic stone treatment in patients with neurogenic bladder. J Urol, 2013. 190: 1479.

https://www.ncbi.nlm.nih.gov/pubmed/23454151

386.Klingler, H.C., et al. Urolithiasis in allograft kidneys. Urology, 2002. 59: 344.

https://www.ncbi.nlm.nih.gov/pubmed/11880067

387.Harper, J.M., et al. Risk factors for calculus formation in patients with renal transplants. Br J Urol, 1994. 74: 147.

https://www.ncbi.nlm.nih.gov/pubmed/7921929

388.Cheungpasitporn, W., et al. Incidence of kidney stones in kidney transplant recipients: A systematic review and meta-analysis. World J Transplant, 2016. 6: 790.

https://www.ncbi.nlm.nih.gov/pubmed/28058231

389.Gupta, M., et al. Treatment of stones associated with complex or anomalous renal anatomy.
Urol Clin North Am, 2007. 34: 431.

https://www.ncbi.nlm.nih.gov/pubmed/17678992

390.Challacombe, B., et al. Multimodal management of urolithiasis in renal transplantation. BJU Int, 2005. 96: 385.

https://www.ncbi.nlm.nih.gov/pubmed/16042735

391.Rifaioglu, M.M., et al. Percutaneous management of stones in transplanted kidneys. Urology, 2008. 72: 508.

https://www.ncbi.nlm.nih.gov/pubmed/18653217

392.Minon Cifuentes, J., et al. Percutaneous nephrolithotomy in transplanted kidney. Urology, 1991.
38: 232.

https://www.ncbi.nlm.nih.gov/pubmed/1887537

393.Wyatt, J., et al. Treatment outcomes for percutaneous nephrolithotomy in renal allografts.
J Endourol, 2009. 23: 1821.

https://www.ncbi.nlm.nih.gov/pubmed/19814697

394.Del Pizzo, J.J., et al. Ureteroscopic evaluation in renal transplant recipients. J Endourol, 1998.
12: 135.

https://www.ncbi.nlm.nih.gov/pubmed/9607439

395.Basiri, A., et al. Ureteroscopic management of urological complications after renal transplantation. Scand J Urol Nephrol, 2006. 40: 53.

https://www.ncbi.nlm.nih.gov/pubmed/16452057

396.Lu, H.F., et al. Donor-gifted allograft urolithiasis: early percutaneous management. Urology, 2002. 59: 25.

https://www.ncbi.nlm.nih.gov/pubmed/11796274

397.Parkhomenko, E., et al. Percutaneous Management of Stone Containing Calyceal Diverticula: Associated Factors and Outcomes. J Urol, 2017. 198: 864.

https://www.ncbi.nlm.nih.gov/pubmed/28483573

398.Bas, O., et al. Management of calyceal diverticular calculi: a comparison of percutaneous nephrolithotomy and flexible ureterorenoscopy. Urolithiasis, 2015. 43: 155.

https://www.ncbi.nlm.nih.gov/pubmed/25249328

399.Raboy, A., et al. Laparoscopic ureterolithotomy. Urology, 1992. 39: 223.

https://www.ncbi.nlm.nih.gov/pubmed/1532102

400.Gaur, D.D. Retroperitoneal endoscopic ureterolithotomy: our experience in 12 patients. J Endourol, 1993. 7: 501.

https://www.ncbi.nlm.nih.gov/pubmed/8124346

401.Gaur, D.D. Retroperitoneal laparoscopic ureterolithotomy. World J Urol, 1993. 11: 175.

https://www.ncbi.nlm.nih.gov/pubmed/8401638

402.Gaur, D.D., et al. Retroperitoneal laparoscopic pyelolithotomy. J Urol, 1994. 151: 927.

https://www.ncbi.nlm.nih.gov/pubmed/8126827

403.Locke, D.R., et al. Extracorporeal shock-wave lithotripsy in horseshoe kidneys. Urology, 1990.
35: 407.

https://www.ncbi.nlm.nih.gov/pubmed/2336770

404.Gelet, A., et al. Endopyelotomy with the Acucise cutting balloon device. Early clinical experience. Eur Urol, 1997. 31: 389.

https://www.ncbi.nlm.nih.gov/pubmed/9187895

405.Faerber, G.J., et al. Retrograde treatment of ureteropelvic junction obstruction using the ureteral cutting balloon catheter. J Urol, 1997. 157: 454.

https://www.ncbi.nlm.nih.gov/pubmed/8996330

406.Berkman, D.S., et al. Treatment outcomes after endopyelotomy performed with or without simultaneous nephrolithotomy: 10-year experience. J Endourol, 2009. 23: 1409.

https://www.ncbi.nlm.nih.gov/pubmed/19694529

407.Nakada, S.Y., et al. Retrospective analysis of the effect of crossing vessels on successful retrograde endopyelotomy outcomes using spiral computerized tomography angiography. J Urol, 1998.
159: 62.

https://www.ncbi.nlm.nih.gov/pubmed/9400437

408.Skolarikos, A., et al. Ureteropelvic obstruction and renal stones: etiology and treatment. Urolithiasis, 2015. 43: 5.

https://www.ncbi.nlm.nih.gov/pubmed/25362543

409.Edvardsson, V.O., et al. Incidence of kidney stone disease in Icelandic children and adolescents from 1985 to 2013: results of a nationwide study. Pediatr Nephrol, 2018. 33: 1375.

https://www.ncbi.nlm.nih.gov/pubmed/29626242

410.Sas, D.J., et al. Increasing incidence of kidney stones in children evaluated in the emergency department. J Pediatr, 2010. 157: 132.

https://www.ncbi.nlm.nih.gov/pubmed/20362300

411.Dwyer, M.E., et al. Temporal trends in incidence of kidney stones among children: a 25-year population based study. J Urol, 2012. 188: 247.

https://www.ncbi.nlm.nih.gov/pubmed/22595060

412.VanDervoort, K., et al. Urolithiasis in pediatric patients: a single center study of incidence, clinical presentation and outcome. J Urol, 2007. 177: 2300.

https://www.ncbi.nlm.nih.gov/pubmed/17509344

413.Matlaga, B.R., et al. Epidemiologic insights into pediatric kidney stone disease. Urol Res, 2010.
38: 453.

https://www.ncbi.nlm.nih.gov/pubmed/20967433

414.Alfandary, H., et al. Increasing Prevalence of Nephrolithiasis in Association with Increased Body Mass Index in Children: A Population Based Study. J Urol, 2018. 199: 1044.

https://www.ncbi.nlm.nih.gov/pubmed/29061537

415.Novak, T.E., et al. Sex prevalence of pediatric kidney stone disease in the United States:
an epidemiologic investigation. Urology, 2009. 74: 104.

https://www.ncbi.nlm.nih.gov/pubmed/19428065

416.Tasian, G.E., et al. Annual Incidence of Nephrolithiasis among Children and Adults in South Carolina from 1997 to 2012. Clin J Am Soc Nephrol, 2016. 11: 488.

https://www.ncbi.nlm.nih.gov/pubmed/26769765

417.Lieske, J.C., et al. Stone composition as a function of age and sex. Clin J Am Soc Nephrol, 2014.
9: 2141.

https://www.ncbi.nlm.nih.gov/pubmed/25278549

418.Bevill, M., et al. The Modern Metabolic Stone Evaluation in Children. Urology, 2017. 101: 15.

https://www.ncbi.nlm.nih.gov/pubmed/27838366

419.Kovacevic, L., et al. From hypercalciuria to hypocitraturia--a shifting trend in pediatric urolithiasis?
J Urol, 2012. 188: 1623.

https://www.ncbi.nlm.nih.gov/pubmed/22910255

420.Cambareri, G.M., et al. National multi-institutional cooperative on urolithiasis in children: Age is a significant predictor of urine abnormalities. J Pediatr Urol, 2015. 11: 218.

https://www.ncbi.nlm.nih.gov/pubmed/26119451

421.Braun, D.A., et al. Prevalence of Monogenic Causes in Pediatric Patients with Nephrolithiasis or Nephrocalcinosis. Clin J Am Soc Nephrol, 2016. 11: 664.

https://www.ncbi.nlm.nih.gov/pubmed/26787776

422.Kant, A.K., et al. Contributors of water intake in US children and adolescents: associations with dietary and meal characteristics--National Health and Nutrition Examination Survey 2005-2006.
Am J Clin Nutr, 2010. 92: 887.

https://www.ncbi.nlm.nih.gov/pubmed/20685949

423.Cogswell, M.E., et al. Vital signs: sodium intake among U.S. school-aged children - 2009-2010. MMWR Morb Mortal Wkly Rep, 2014. 63: 789.

https://www.ncbi.nlm.nih.gov/pubmed/25211544

424.Clark, M.A., et al. Nutritional quality of the diets of US public school children and the role of the school meal programs. J Am Diet Assoc, 2009. 109: S44.

https://www.ncbi.nlm.nih.gov/pubmed/19166672

425.Marzuillo, P., et al. Why we need a higher suspicion index of urolithiasis in children. J Pediatr Urol, 2017. 13: 164.

https://www.ncbi.nlm.nih.gov/pubmed/28185760

426.Andrioli, V., et al. Infant nephrolithiasis and nephrocalcinosis: Natural history and predictors of surgical intervention. J Pediatr Urol, 2017. 13: 355 e1.

https://www.ncbi.nlm.nih.gov/pubmed/28729176

427.Issler, N., et al. Epidemiology of paediatric renal stone disease: a 22-year single centre experience in the UK. BMC Nephrol, 2017. 18: 136.

https://www.ncbi.nlm.nih.gov/pubmed/28420322

428.Sas, D.J., et al. Clinical, demographic, and laboratory characteristics of children with nephrolithiasis. Urolithiasis, 2016. 44: 241.

https://www.ncbi.nlm.nih.gov/pubmed/26467033

429.Telli, O., et al. What happens to asymptomatic lower pole kidney stones smaller than 10 mm in children during watchful waiting? Pediatr Nephrol, 2017. 32: 853.

https://www.ncbi.nlm.nih.gov/pubmed/28070668

430.Dos Santos, J., et al. Outcome Analysis of Asymptomatic Lower Pole Stones in Children. J Urol, 2016. 195: 1289.

https://www.ncbi.nlm.nih.gov/pubmed/26926554

431.Dincel, N., et al. Are small residual stone fragments really insignificant in children? J Pediatr Surg, 2013. 48: 840.

https://www.ncbi.nlm.nih.gov/pubmed/23583144

432.Tian, D., et al. The efficacy and safety of adrenergic alpha-antagonists in treatment of distal ureteral stones in pediatric patients: A systematic review and meta-analysis. J Pediatr Surg, 2017. 52: 360.

https://www.ncbi.nlm.nih.gov/pubmed/27837990

433.Barreto, L., et al. Medical and surgical interventions for the treatment of urinary stones in children. Cochrane Database Syst Rev, 2018. 6: CD010784.

https://www.ncbi.nlm.nih.gov/pubmed/29859007

434.Lu, P., et al. The clinical efficacy of extracorporeal shock wave lithotripsy in pediatric urolithiasis:
a systematic review and meta-analysis. Urolithiasis, 2015. 43: 199.

https://www.ncbi.nlm.nih.gov/pubmed/25721456

435.Dogan, H.S., et al. A new nomogram for prediction of outcome of pediatric shock-wave lithotripsy.
J Pediatr Urol, 2015. 11: 84 e1.

https://www.ncbi.nlm.nih.gov/pubmed/25812469

436.Alsagheer, G., et al. Extracorporeal shock wave lithotripsy (ESWL) monotherapy in children: Predictors of successful outcome. J Pediatr Urol, 2017. 13: 515 e1.

https://www.ncbi.nlm.nih.gov/pubmed/28457667

437.Zeng, G., et al. Treatment of renal stones in infants: comparing extracorporeal shock wave lithotripsy and mini-percutaneous nephrolithotomy. Urol Res, 2012. 40: 599.

https://www.ncbi.nlm.nih.gov/pubmed/22580634

438.Badawy, A.A., et al. Extracorporeal shock wave lithotripsy as first line treatment for urinary tract stones in children: outcome of 500 cases. Int Urol Nephrol, 2012. 44: 661.

https://www.ncbi.nlm.nih.gov/pubmed/22350835

439.Jee, J.Y., et al. Efficacy of extracorporeal shock wave lithotripsy in pediatric and adolescent urolithiasis. Korean J Urol, 2013. 54: 865.

https://www.ncbi.nlm.nih.gov/pubmed/24363869

440.Dobrowiecka, K., et al. Early complications of extracorporeal shockwave lithotripsy in the records of the Department of Paediatrics, Nephrology and Allergology of the Military Institute of Medicine - preliminary results. Dev Period Med, 2018. 22: 260.

https://www.ncbi.nlm.nih.gov/pubmed/30281522

441.Cevik, B., et al. Procedural sedation and analgesia for pediatric shock wave lithotripsy: a 10 year experience of single institution. Urolithiasis, 2018. 46: 363.

https://www.ncbi.nlm.nih.gov/pubmed/28642966

442.Kumar, A., et al. A Single Center Experience Comparing Miniperc and Shockwave Lithotripsy for Treatment of Radiopaque 1-2 cm Lower Caliceal Renal Calculi in Children: A Prospective Randomized Study. J Endourol, 2015. 29: 805.

https://www.ncbi.nlm.nih.gov/pubmed/25633506

443.Wang, H.H., et al. Shock wave lithotripsy vs ureteroscopy: variation in surgical management of kidney stones at freestanding children’s hospitals. J Urol, 2012. 187: 1402.

https://www.ncbi.nlm.nih.gov/pubmed/22341283

444.Jurkiewicz, B., et al. Ureterolithotripsy in a paediatric population: a single institution’s experience. Urolithiasis, 2014. 42: 171.

https://www.ncbi.nlm.nih.gov/pubmed/24368682

445.Elsheemy, M.S., et al. Holmium:YAG laser ureteroscopic lithotripsy for ureteric calculi in children: predictive factors for complications and success. World J Urol, 2014. 32: 985.

https://www.ncbi.nlm.nih.gov/pubmed/23979150

446.Ishii, H., et al. Ureteroscopy for stone disease in the paediatric population: a systematic review.
BJU Int, 2015. 115: 867.

https://www.ncbi.nlm.nih.gov/pubmed/25203925

447.Tanriverdi, O., et al. Comparison of ureteroscopic procedures with rigid and semirigid ureteroscopes in pediatric population: does the caliber of instrument matter? Pediatr Surg Int, 2010. 26: 733.

https://www.ncbi.nlm.nih.gov/pubmed/20521057

448.Dogan, H.S., et al. Factors affecting complication rates of ureteroscopic lithotripsy in children: results of multi-institutional retrospective analysis by Pediatric Stone Disease Study Group of Turkish Pediatric Urology Society. J Urol, 2011. 186: 1035.

https://www.ncbi.nlm.nih.gov/pubmed/21784482

449.Gokce, M.I., et al. Effect of Prestenting on Success and Complication Rates of Ureterorenoscopy in Pediatric Population. J Endourol, 2016. 30: 850.

https://www.ncbi.nlm.nih.gov/pubmed/27189236

450.Ellison, J.S., et al. Risk factors for repeat surgical intervention in pediatric nephrolithiasis: A Pediatric Health Information System database study. J Pediatr Urol, 2018. 14: 245 e1.

https://www.ncbi.nlm.nih.gov/pubmed/20521057

451.Unsal, A., et al. Retrograde intrarenal surgery in infants and preschool-age children. J Pediatr Surg, 2011. 46: 2195.

https://www.ncbi.nlm.nih.gov/pubmed/22075358

452.Cannon, G.M., et al. Ureteroscopic management of lower-pole stones in a pediatric population.
J Endourol, 2007. 21: 1179.

https://www.ncbi.nlm.nih.gov/pubmed/17949321

453.Erkurt, B., et al. Treatment of renal stones with flexible ureteroscopy in preschool age children. Urolithiasis, 2014. 42: 241.

https://www.ncbi.nlm.nih.gov/pubmed/24374900

454.Kim, S.S., et al. Pediatric flexible ureteroscopic lithotripsy: the children’s hospital of Philadelphia experience. J Urol, 2008. 180: 2616.

https://www.ncbi.nlm.nih.gov/pubmed/18950810

455.Suliman, A., et al. Flexible ureterorenoscopy to treat upper urinary tract stones in children. Urolithiasis, 2018.

https://www.ncbi.nlm.nih.gov/pubmed/30370467

456.Xiao, J., et al. Treatment of upper urinary tract stones with flexible ureteroscopy in children. Can Urol Assoc J, 2018.

https://www.ncbi.nlm.nih.gov/pubmed/30169147

457.Tiryaki, T., et al. Ureteroscopy for treatment of ureteral stones in children: factors influencing the outcome. Urology, 2013. 81: 1047.

https://www.ncbi.nlm.nih.gov/pubmed/23465154

458.Mokhless, I.A., et al. Retrograde intrarenal surgery monotherapy versus shock wave lithotripsy for stones 10 to 20 mm in preschool children: a prospective, randomized study. J Urol, 2014.
191: 1496.

https://www.ncbi.nlm.nih.gov/pubmed/24679882

459.Saad, K.S., et al. Percutaneous Nephrolithotomy vs Retrograde Intrarenal Surgery for Large Renal Stones in Pediatric Patients: A Randomized Controlled Trial. J Urol, 2015. 194: 1716.

https://www.ncbi.nlm.nih.gov/pubmed/26165587

460.Pelit, E.S., et al. Comparison of Mini-percutaneous Nephrolithotomy and Retrograde Intrarenal Surgery in Preschool-aged Children. Urology, 2017. 101: 21.

https://www.ncbi.nlm.nih.gov/pubmed/27818164

461.Bas, O., et al. Comparison of Retrograde Intrarenal Surgery and Micro-Percutaneous Nephrolithotomy in Moderately Sized Pediatric Kidney Stones. J Endourol, 2016. 30: 765.

https://www.ncbi.nlm.nih.gov/pubmed/26983791

462.Chen, Y., et al. Percutaneous nephrolithotomy versus retrograde intrarenal surgery for pediatric patients with upper urinary stones: a systematic review and meta-analysis. Urolithiasis, 2018.

https://www.ncbi.nlm.nih.gov/pubmed/29368009

463.Cicekbilek, I., et al. Effect of percutaneous nephrolithotomy on renal functions in children: assessment by quantitative SPECT of (99m)Tc-DMSA uptake by the kidneys. Ren Fail, 2015.
37: 1118.

https://www.ncbi.nlm.nih.gov/pubmed/26067745

464.Daggulli, M., et al. Micro-percutaneous nephrolithotomy in the treatment of pediatric nephrolithiasis: A single-center experience. J Pediatr Surg, 2016. 51: 626.

https://www.ncbi.nlm.nih.gov/pubmed/26460156

465.Celik, H., et al. Comparison of the results of pediatric percutaneous nephrolithotomy with different sized instruments. Urolithiasis, 2017. 45: 203.

https://www.ncbi.nlm.nih.gov/pubmed/27155829

466.Dombrovskiy, V., et al. Percutaneous Nephrolithotomy in Children: Analysis of Nationwide Hospitalizations and Short-Term Outcomes for the United States, 2001-2014. J Endourol, 2018.
32: 912.

https://www.ncbi.nlm.nih.gov/pubmed/30113212

467.Senocak, C., et al. Predictive factors of bleeding among pediatric patients undergoing percutaneous nephrolithotomy. Urolithiasis, 2018. 46: 383.

https://www.ncbi.nlm.nih.gov/pubmed/28702679

468.Jones, P., et al. Role of Minimally Invasive Percutaneous Nephrolithotomy Techniques-Micro and Ultra-Mini PCNL (<15F) in the Pediatric Population: A Systematic Review. J Endourol, 2017. 31: 816.

https://www.ncbi.nlm.nih.gov/pubmed/28478724

469.Guven, S., et al. Percutaneous nephrolithotomy in children in different age groups: data from the Clinical Research Office of the Endourological Society (CROES) Percutaneous Nephrolithotomy Global Study. BJU Int, 2013. 111: 148.

https://www.ncbi.nlm.nih.gov/pubmed/22578216

470.Onal, B., et al. Factors affecting complication rates of percutaneous nephrolithotomy in children: results of a multi-institutional retrospective analysis by the Turkish pediatric urology society. J Urol, 2014. 191: 777.

https://www.ncbi.nlm.nih.gov/pubmed/24095906

471.Aghamir, S.M., et al. Comparing Bleeding Complications of Double and Single Access Totally Tubeless PCNL: Is It Safe to Obtain More Accesses? Urol Int, 2016. 96: 73.

https://www.ncbi.nlm.nih.gov/pubmed/26021886

472.Iqbal, N., et al. Comparison of outcomes of tubed versus tubeless percutaneous nephrolithotomy in children: A single center study. Turk J Urol, 2018. 44: 56.

https://www.ncbi.nlm.nih.gov/pubmed/29484229

473.Samad, L., et al. Does percutaneous nephrolithotomy in children cause significant renal scarring?
J Pediatr Urol, 2007. 3: 36.

https://www.ncbi.nlm.nih.gov/pubmed/18947696

474.Modi, P.K., et al. Pediatric hospitalizations for upper urinary tract calculi: Epidemiological and treatment trends in the United States, 2001-2014. J Pediatr Urol, 2018. 14: 13 e1.

https://www.ncbi.nlm.nih.gov/pubmed/28966022

475.Agrawal, V., et al. Laparoscopic management of pediatric renal and ureteric stones. J Pediatr Urol, 2013. 9: 230.

https://www.ncbi.nlm.nih.gov/pubmed/22498008

476.Srivastava, A., et al. Laparoscopic Ureterolithotomy in Children: With and Without Stent - Initial Tertiary Care Center Experience with More Than 1-Year Follow-Up. Eur J Pediatr Surg, 2017.
27: 150.

https://www.ncbi.nlm.nih.gov/pubmed/26878339

477.Lee, R.S., et al. Early results of robot assisted laparoscopic lithotomy in adolescents. J Urol, 2007. 177: 2306.

https://www.ncbi.nlm.nih.gov/pubmed/17509345

478.Parks, J.H., et al. A single 24-hour urine collection is inadequate for the medical evaluation of nephrolithiasis. J Urol, 2002. 167: 1607.

https://www.ncbi.nlm.nih.gov/pubmed/11912373

479.Nayan, M., et al. Variations between two 24-hour urine collections in patients presenting to a tertiary stone clinic. Can Urol Assoc J, 2012. 6: 30.

https://www.ncbi.nlm.nih.gov/pubmed/22396364

480.Ferraz, R.R., et al. Preservation of urine samples for metabolic evaluation of stone-forming patients. Urol Res, 2006. 34: 329.

https://www.ncbi.nlm.nih.gov/pubmed/16896690

481.Yilmaz, G., et al. Are preservatives necessary in 24-hour urine measurements? Clin Biochem, 2008. 41: 899.

https://www.ncbi.nlm.nih.gov/pubmed/18371307

482.Coe, F.L., et al. Kidney stone disease. J Clin Invest, 2005. 115: 2598.

https://www.ncbi.nlm.nih.gov/pubmed/16200192

483.Norman, R.W., et al. When should patients with symptomatic urinary stone disease be evaluated metabolically? J Urol, 1984. 132: 1137.

https://www.ncbi.nlm.nih.gov/pubmed/6502804

484.Urine evaluation (In: Evaluation of the stone former), in 2ND International Consultation on Stone Disease, H.M. Assimos D. Chew B, Hautmann R, Holmes R, Williams J, Wolf JS, Editor. 2007, Health Publications.

485.Hesse A, T.H., Jahnen A., Urinary Stones: Diagnosis, Treatment and Prevention of Recurrence.,
In: Uric acid stones. 2002, S Karger AG,: Basel.

486.Tiselius, H.G. Standardized estimate of the ion activity product of calcium oxalate in urine from renal stone formers. Eur Urol, 1989. 16: 48.

https://www.ncbi.nlm.nih.gov/pubmed/2714318

487.Ackermann, D., et al. Use of the computer program EQUIL to estimate pH in model solutions and human urine. Urol Res, 1989. 17: 157.

https://www.ncbi.nlm.nih.gov/pubmed/2749945

488.Kavanagh, J.P., et al. Why does the Bonn Risk Index discriminate between calcium oxalate stone formers and healthy controls? J Urol, 2006. 175: 766.

https://www.ncbi.nlm.nih.gov/pubmed/16407047

489.Rodgers AL, et al. What can it teach us?, In: Proceedings of Renal Stone Disease 1st Annual International Urolithiasis Research Symposium, 2-3 November 2006., Evan A.P., Lingeman J.E. Eds. 2007, American Institute of Physics: Melville, New York.

490.Hoppe, B., et al. Diagnostic examination of the child with urolithiasis or nephrocalcinosis.
Pediatr Nephrol, 2010. 25: 403.

https://www.ncbi.nlm.nih.gov/pubmed/19104842

491.Katarzyna, T.-J., et al. Determining normal values of urinary phosphorus excretion in 3913 healthy children aged 2–18 to aid early diagnosis and treatment for urolithiasis. Acta Paediatrica, 2017.
106: 1170.

https://www.ncbi.nlm.nih.gov/pubmed/28370428

492.Borghi, L., et al. Urinary volume, water and recurrences in idiopathic calcium nephrolithiasis:
a 5-year randomized prospective study. J Urol, 1996. 155: 839.

https://www.ncbi.nlm.nih.gov/pubmed/8583588

493.Sarica, K., et al. The effect of calcium channel blockers on stone regrowth and recurrence after shock wave lithotripsy. Urol Res, 2006. 34: 184.

https://www.ncbi.nlm.nih.gov/pubmed/16463053

494.Fink, H.A., et al. Medical management to prevent recurrent nephrolithiasis in adults: a systematic review for an American College of Physicians Clinical Guideline. Ann Intern Med, 2013. 158: 535.

https://www.ncbi.nlm.nih.gov/pubmed/23546565

495.Siener, R., et al. Dietary risk factors for hyperoxaluria in calcium oxalate stone formers. Kidney Int, 2003. 63: 1037.

https://www.ncbi.nlm.nih.gov/pubmed/12631085

496.Wabner, C.L., et al. Effect of orange juice consumption on urinary stone risk factors. J Urol, 1993. 149: 1405.

https://www.ncbi.nlm.nih.gov/pubmed/8501777

497.Gettman, M.T., et al. Effect of cranberry juice consumption on urinary stone risk factors. J Urol, 2005. 174: 590.

https://www.ncbi.nlm.nih.gov/pubmed/16006907

498.Shuster, J., et al. Soft drink consumption and urinary stone recurrence: a randomized prevention trial. J Clin Epidemiol, 1992. 45: 911.

https://www.ncbi.nlm.nih.gov/pubmed/1624973

499.Kocvara, R., et al. A prospective study of nonmedical prophylaxis after a first kidney stone. BJU Int, 1999. 84: 393.

https://www.ncbi.nlm.nih.gov/pubmed/10468751

500.Hess, B., et al. Effects of a ‘common sense diet’ on urinary composition and supersaturation in patients with idiopathic calcium urolithiasis. Eur Urol, 1999. 36: 136.

https://www.ncbi.nlm.nih.gov/pubmed/10420035

501.Ebisuno, S., et al. Results of long-term rice bran treatment on stone recurrence in hypercalciuric patients. Br J Urol, 1991. 67: 237.

https://www.ncbi.nlm.nih.gov/pubmed/1902388

502.Hiatt, R.A., et al. Randomized controlled trial of a low animal protein, high fiber diet in the prevention of recurrent calcium oxalate kidney stones. Am J Epidemiol, 1996. 144: 25.

https://www.ncbi.nlm.nih.gov/pubmed/8659482

503.Dussol, B., et al. A randomized trial of low-animal-protein or high-fiber diets for secondary prevention of calcium nephrolithiasis. Nephron Clin Pract, 2008. 110: c185.

https://www.ncbi.nlm.nih.gov/pubmed/18957869

504.Turney, B.W., et al. Diet and risk of kidney stones in the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). Eur J Epidemiol, 2014. 29: 363.

https://www.ncbi.nlm.nih.gov/pubmed/24752465

505.Auer, B.L., et al. The effect of ascorbic acid ingestion on the biochemical and physicochemical risk factors associated with calcium oxalate kidney stone formation. Clin Chem Lab Med, 1998. 36: 143.

https://www.ncbi.nlm.nih.gov/pubmed/9589801

506.Borghi, L., et al. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med, 2002. 346: 77.

https://www.ncbi.nlm.nih.gov/pubmed/11784873

507.Fink, H.A., et al. Diet, fluid, or supplements for secondary prevention of nephrolithiasis: a systematic review and meta-analysis of randomized trials. Eur Urol, 2009. 56: 72.

https://www.ncbi.nlm.nih.gov/pubmed/19321253

508.Curhan, G.C., et al. Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med, 1997. 126: 497.

https://www.ncbi.nlm.nih.gov/pubmed/9092314

509.von Unruh, G.E., et al. Dependence of oxalate absorption on the daily calcium intake. J Am Soc Nephrol, 2004. 15: 1567.

https://www.ncbi.nlm.nih.gov/pubmed/15153567

510.Harris, S.S., et al. Effects of Hydration and Calcium Supplementation on Urine Calcium Concentration in Healthy Postmenopausal Women. J Am Coll Nutr, 2015. 34: 340.

https://www.ncbi.nlm.nih.gov/pubmed/25856469

511.Curhan, G.C., et al. A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. N Engl J Med, 1993. 328: 833.

https://www.ncbi.nlm.nih.gov/pubmed/8441427

512.Coe, F.L. Hyperuricosuric calcium oxalate nephrolithiasis. Adv Exp Med Biol, 1980. 128: 439.

https://www.ncbi.nlm.nih.gov/pubmed/7424690

513.Hyperuricosuric calcium stone disease, In: Kidney Stones: Medical and Surgical Management,
Coe FL, Pak CYC, Parks JH, Preminger GM, Eds. 1996, Lippincott-Raven: Philadelphia.

514.Siener, R., et al. The role of overweight and obesity in calcium oxalate stone formation. Obes Res, 2004. 12: 106.

https://www.ncbi.nlm.nih.gov/pubmed/14742848

515.Madore, F., et al. Nephrolithiasis and risk of hypertension. Am J Hypertens, 1998. 11: 46.

https://www.ncbi.nlm.nih.gov/pubmed/9504449

516.Madore, F., et al. Nephrolithiasis and risk of hypertension in women. Am J Kidney Dis, 1998. 32: 802.

https://www.ncbi.nlm.nih.gov/pubmed/9820450

517.Tiselius, H.G., et al. Effects of citrate on the different phases of calcium oxalate crystallization. Scanning Microsc, 1993. 7: 381.

https://www.ncbi.nlm.nih.gov/pubmed/8316807

518.Barcelo, P., et al. Randomized double-blind study of potassium citrate in idiopathic hypocitraturic calcium nephrolithiasis. J Urol, 1993. 150: 1761.

https://www.ncbi.nlm.nih.gov/pubmed/8230497

519.Hofbauer, J., et al. Alkali citrate prophylaxis in idiopathic recurrent calcium oxalate urolithiasis--
a prospective randomized study. Br J Urol, 1994. 73: 362.

https://www.ncbi.nlm.nih.gov/pubmed/8199822

520.Ettinger, B., et al. Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. J Urol, 1997. 158: 2069.

https://www.ncbi.nlm.nih.gov/pubmed/9366314

521.Soygur, T., et al. Effect of potassium citrate therapy on stone recurrence and residual fragments after shockwave lithotripsy in lower caliceal calcium oxalate urolithiasis: a randomized controlled trial.
J Endourol, 2002. 16: 149.

https://www.ncbi.nlm.nih.gov/pubmed/12028622

522.Premgamone, A., et al. A long-term study on the efficacy of a herbal plant, Orthosiphon grandiflorus, and sodium potassium citrate in renal calculi treatment. Southeast Asian J Trop Med Public Health, 2001. 32: 654.

https://www.ncbi.nlm.nih.gov/pubmed/11944733

523.Lojanapiwat, B., et al. Alkaline citrate reduces stone recurrence and regrowth after shockwave lithotripsy and percutaneous nephrolithotomy. Int Braz J Urol, 2011. 37: 611.

https://www.ncbi.nlm.nih.gov/pubmed/22099273

524.Phillips, R., et al. Citrate salts for preventing and treating calcium containing kidney stones in adults. Cochrane Database Syst Rev, 2015: CD010057.

https://www.ncbi.nlm.nih.gov/pubmed/26439475

525.Favus, M.J., et al. The effects of allopurinol treatment on stone formation on hyperuricosuric calcium oxalate stone-formers. Scand J Urol Nephrol Suppl, 1980. 53: 265.

https://www.ncbi.nlm.nih.gov/pubmed/6938003

526.Miano L, et al. A placebo controlled double-blind study of allopurinol in severe recurrent idiopathic renal lithiasis, In: Urolithiasis and Related Clinical Research. Schwille PO, Robertson WG, Vahlensieck W., Eds. 1985, Plenum Press: New York.

527.Ettinger, B., et al. Randomized trial of allopurinol in the prevention of calcium oxalate calculi. N Engl J Med, 1986. 315: 1386.

https://www.ncbi.nlm.nih.gov/pubmed/3534570

528.Robertson, W.G., et al., A Multicentre Trial to Evaluate Three Treatments for Recurrent Idiopathic Calcium Stone Disease — A Preliminary Report, In: Urolithiasis and Related Clinical Research, Schwille P., Smith L., Robertson W. & Vahlensieck W., Editors. 1985, Springer US.

529.Smith, M.J. Placebo versus allopurinol for renal calculi. J Urol, 1977. 117: 690.

https://www.ncbi.nlm.nih.gov/pubmed/875139

530.Cohen, T.D., et al. Clinical effect of captopril on the formation and growth of cystine calculi. J Urol, 1995. 154: 164.

https://www.ncbi.nlm.nih.gov/pubmed/7776415

531.Coulthard, M.G., et al. The treatment of cystinuria with captopril. Am J Kidney Dis, 1995. 25: 661.

https://www.ncbi.nlm.nih.gov/pubmed/7702068

532.Goldfarb, D.S., et al. Randomized controlled trial of febuxostat versus allopurinol or placebo in individuals with higher urinary uric acid excretion and calcium stones. Clin J Am Soc Nephrol, 2013. 8: 1960.

https://www.ncbi.nlm.nih.gov/pubmed/23929928

533.Nouvenne, A., et al. New pharmacologic approach to patients with idiopathic calcium nephrolithiasis and high uricosuria: Febuxostat vs allopurinol. A pilot study. Eur J Int Med. 24: e64.

https://www.ejinme.com/article/S0953-6205(13)00364-6/fulltext

534.Jarrar, K., et al. Struvite stones: long term follow up under metaphylaxis. Ann Urol (Paris), 1996.
30: 112.

https://www.ncbi.nlm.nih.gov/pubmed/8766146

535.Hesse, A., et al. Causes of phosphate stone formation and the importance of metaphylaxis by urinary acidification: a review. World J Urol, 1999. 17: 308.

https://www.ncbi.nlm.nih.gov/pubmed/10552150

536.Ettinger, B., et al. Chlorthalidone reduces calcium oxalate calculous recurrence but magnesium hydroxide does not. J Urol, 1988. 139: 679.

https://www.ncbi.nlm.nih.gov/pubmed/3280829

537.Prien, E.L., Sr., et al. Magnesium oxide-pyridoxine therapy for recurrent calcium oxalate calculi.
J Urol, 1974. 112: 509.

https://www.ncbi.nlm.nih.gov/pubmed/4414543

538.Pinheiro, V.B., et al. The effect of sodium bicarbonate upon urinary citrate excretion in calcium stone formers. Urology, 2013. 82: 33.

https://www.ncbi.nlm.nih.gov/pubmed/23602798

539.Hoppe, B., et al. The primary hyperoxalurias. Kidney Int, 2009. 75: 1264.

https://www.ncbi.nlm.nih.gov/pubmed/19225556

540.Borghi, L., et al. Randomized prospective study of a nonthiazide diuretic, indapamide, in preventing calcium stone recurrences. J Cardiovasc Pharmacol, 1993. 22 Suppl 6: S78.

https://www.ncbi.nlm.nih.gov/pubmed/7508066

541.Brocks, P., et al. Do thiazides prevent recurrent idiopathic renal calcium stones? Lancet, 1981.
2: 124.

https://www.ncbi.nlm.nih.gov/pubmed/6361755

542.Mortensen, J.T., et al. Thiazides in the prophylactic treatment of recurrent idiopathic kidney stones. Int Urol Nephrol, 1986. 18: 265.

https://www.ncbi.nlm.nih.gov/pubmed/3533825

543.Laerum, E., et al. Thiazide prophylaxis of urolithiasis. A double-blind study in general practice.
Acta Med Scand, 1984. 215: 383.

https://www.ncbi.nlm.nih.gov/pubmed/6375276

544.Ohkawa, M., et al. Thiazide treatment for calcium urolithiasis in patients with idiopathic hypercalciuria. Br J Urol, 1992. 69: 571.

https://www.ncbi.nlm.nih.gov/pubmed/1638340

545.Scholz, D., et al. Double-blind study with thiazide in recurrent calcium lithiasis. J Urol, 1982.
128: 903.

https://www.ncbi.nlm.nih.gov/pubmed/7176047

546.Nicar, M.J., et al. Use of potassium citrate as potassium supplement during thiazide therapy of calcium nephrolithiasis. J Urol, 1984. 131: 430.

https://www.ncbi.nlm.nih.gov/pubmed/6699979

547.Fernandez-Rodriguez, A., et al. [The role of thiazides in the prophylaxis of recurrent calcium lithiasis]. Actas Urol Esp, 2006. 30: 305.

https://www.ncbi.nlm.nih.gov/pubmed/16749588

548.Ahlstrand, C., et al. Prophylactic treatment of calcium-stone-for

1.INTRODUCTION

1.1.Aims and scope

1.2.Panel composition

1.3.Available publications

1.4.Publication history and summary of changes

1.4.1.Publication history

1.4.2.Summary of changes

2.METHODS

2.1.Data identification

2.2.Review

2.3.Future goals

3.GUIDELINES

3.1.Prevalence, aetiology, risk of recurrence

3.1.1.Introduction

3.1.2.Stone composition

3.1.3.Risk groups for stone formation

3.2.Classification of stones

3.2.1.Stone size

3.2.2.Stone location

3.2.3.X-ray characteristics

3.3.Diagnostic evaluation

3.3.1.Diagnostic imaging

3.3.1.1.Evaluation of patients with acute flank pain/suspected ureteral stones

3.3.1.2.Radiological evaluation of patients with renal stones

3.3.1.3.Summary of evidence and guidelines for diagnostic imaging

3.3.2.Diagnostics - metabolism-related

3.3.2.1.Basic laboratory analysis - non-emergency urolithiasis patients

3.3.2.2.Analysis of stone composition

3.3.2.3.Guidelines for laboratory examinations and stone analysis [16,22,57,64]

3.3.3.Diagnosis in special groups and conditions

3.3.3.1.Diagnostic imaging during pregnancy

3.3.3.1.1.Summary of evidence and guidelines for diagnostic imaging during pregnancy

3.3.3.2.Diagnostic imaging in children

3.3.3.2.1.Summary of evidence and guidelines for diagnostic imaging in children

3.4.Disease Management

3.4.1.Renal colic

3.4.1.1.Summary of evidence and guidelines for the management of renal colic

3.4.2.Management of sepsis and/or anuria in obstructed kidney

3.4.2.1.Summary of evidence and guidelines for the management of sepsis and anuria

3.4.3.Medical expulsive therapy

3.4.3.1.Summary of evidence and guideline for MET

3.4.4.Chemolysis

3.4.4.1.Summary of evidence and guidelines for chemolysis

3.4.5.Extracorporeal shock wave lithotripsy (SWL)

3.4.5.1.Summary of evidence and guidelines for SWL

3.4.6.Ureteroscopy (URS) (retrograde and antegrade, RIRS)

3.4.6.1.Summary of evidence and guidelines for retrograde URS, RIRS and antegrade ureteroscopy

3.4.7.Percutaneous nephrolithotomy

3.4.7.1.Summary of evidence and guidelines for endourology techniques for renal stone removal

3.4.8.General recommendations and precautions for stone removal

3.4.8.1.Antibiotic therapy

3.4.8.2.Antithrombotic therapy and stone treatment

3.4.8.2.1.Summary of evidence and guidelines for antithrombotic therapy and stone treatment

3.4.8.3.Obesity

3.4.8.4.Stone composition

3.4.8.4.1.Guidelines for stone composition

3.4.8.5.Contraindications of procedures

3.4.9.Specific stone management of ureteral stones

3.4.9.1.Conservative treatment/observation

3.4.9.2.Pharmacological treatment, medical explusive therapy

3.4.9.3.Indications for active removal of ureteral stones

3.4.9.4.Selection of procedure for active removal of ureteral stones

3.4.9.4.1.Summary of evidence and guidelines for selection of procedure for active removal of ureteral stones

3.4.10.Specific stone management of renal stones

3.4.10.1.Conservative treatment (observation)

3.4.10.2.Pharmacological treatment of renal stones

3.4.10.3.Indications for active stone removal of renal stones [298]

3.4.10.4.Selection of procedure for active removal of renal stones

3.4.10.4.1.Stones in renal pelvis or upper/middle calices

3.4.10.4.2.Stones in the lower renal pole

3.4.10.5.Summary of evidence and guidelines for the management of renal stones

3.4.11.Laparoscopy and open surgery

3.4.11.1.Summary of evidence and guideline for laparoscopy and open surgery

3.4.12.Steinstrasse

3.4.12.1.Summary of evidence and guidelines for steinstrasse

3.4.13.Management of patients with residual stones

3.4.13.1.Summary of evidence and guideline for management of patients with residual stones

3.4.14.Management of specific patient groups

3.4.14.1.Management of urinary stones and related problems during pregnancy

3.4.14.1.1.Summary of evidence and guideline for the management of urinary stones and related problems during pregnancy