Which intervention would prevent urinary stasis and formation of renal calculi?

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% [9]. 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 [10-12]. There is emerging evidence linking nephrolithiasis to the risk of chronic kidney disease (CKD) [13].

Stones can be stratified into those caused by: infections, non-infectious causes, genetic defects [14]; or adverse drug effects (drug stones) (Table 3.1). See also section 3.2.

Table 3.1: Stones classified by aetiology

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

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, the risk of CKD and mineral and bone disorder, and is imperative for pharmacological treatment. About 50% of recurrent stone formers have just one lifetime recurrence [11,16]. A recent review of first-time stone formers calculated a recurrence rate of 26% in five years’ time [17]. Highly recurrent disease is observed in slightly more than 10% of patients. Stone type and disease severity determine low- or high-risk stone formers (Table 3.3) [18,19].

Table 3.3: High-risk stone formers [18-34]

A comprehensive evaluation of stone risk in patients should also include the risk of developing CKD, end-stage kidney disease (ESKD), and metabolic stone disease (Tables 3.4, 3.5 and 3.6). Urolithiasis can compromise renal function because of the renal stone (obstruction, infection), renal tissue damage due to the primary condition causing stone formation (some genetic diseases, nephrocalcinosis, enteric hyperoxaluria, etc.), or urological treatments for the condition [35]. Certain risk factors have been shown to be associated with such a risk in stone formers, as shown below.

Table 3.4 Risk factors for CKD and ESKD in stone formers

Furthermore, some specific kinds of urolithiasis also carry a particular risk of developing CKD/ESKD as shown below.

Table 3.5 Risk factors for CKD and renal stones

Table 3.6 Risk factors for metabolic bone disease and calcium renal stones

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 [11,36,37].

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.

3.2.3. X-ray characteristics

Stones can be classified according to plain X-ray appearance [kidney-ureter-bladder (KUB) radiography] (Table 3.6), which varies according to mineral composition [37]. 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) [36,37].

Table 3.7: X-ray characteristics

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 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 [38]. 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 calyces, 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 [39,40].

The sensitivity and specificity of KUB is 44-77% [41]. Kidney-ureter-bladder radiography should not be performed if NCCT is being considered [42]; however, it is helpful in differentiating between radiolucent and radiopaque stones and should be used for comparison during follow-up.

Non-contrast-enhanced computed tomography 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 or US [43].

Non-contrast-enhanced CT can detect uric acid and xanthine stones, which are radiolucent on plain films, but not indinavir stones [44]. 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
[37,45-47]. 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 [48-51].

Radiation risk can be reduced by low-dose CT, which may, however, be difficult to introduce in standard clinical practice [52-56]. 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 [57]. A meta-analysis (MA) of prospective studies [54] 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 [58,59].

3.3.2. Diagnostics - metabolism-related

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

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 [19]. 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 in section 3.3.2.3. Once the mineral composition is known, a potential metabolic disorder can be identified.

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 [60,61].

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) [62-64]. Equivalent results can be obtained by polarisation microscopy. Chemical analysis (wet chemistry) is generally deemed to be obsolete [62,65].

3.3.3. Diagnosis in special groups and conditions

In pregnant women radiation exposure may cause non-stochastic (teratogenesis) or stochastic (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 (doses 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 [68].

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 [69], X-ray imaging [70,71], and MRI [72,73] are used as and when indicated [74-80]. 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 [76-78].

Magnetic resonance imaging can be used, as a second-line option [74], to define the level of urinary tract obstruction, and to visualise stones as a filling defect [72]. As 3 Tesla (T) MRI has not been evaluated in pregnancy, the use of 1.5T is currently recommended [75,80]. The use of gadolinium is not routinely recommended in pregnancy to avoid toxic effects to the embryo [76].

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 [81]. Although low-dose CT protocols reduce the radiation exposure, judicious use is currently recommended in pregnant women as a last-line option [76].

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 [82].

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. Again, the principle of ALARA (As Low As Reasonably Achievable) should be observed [83-85].

Ultrasound

Ultrasound is the primary imaging technique [86] 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 [87-91]. Colour Doppler US shows differences in the ureteral jet [88] and resistive index of the arciform arteries of both kidneys, which are indicative of the grade of obstruction [89]. Nevertheless, US fails to identify stones in > 40% of children [90-93] 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

The radiation dose for IVU is comparable to that for voiding cysto-urethrography (0.33 mSV) [94]. However, the need for contrast medium injection is a major drawback.

Non-contrast-enhanced computed tomography

Recent low-dose CT protocols have been shown to significantly reduce radiation exposure [51,95,96]. In children, only 5% of stones escape detection by NCCT [88,96,97]. Sedation or anaesthesia is rarely needed with modern high-speed CT equipment.

Magnetic resonance urography

Magnetic resonance urography (MRU) 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 [98].

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 [99], and have better analgesic efficacy than opioids [100]. Ibuprofen compared to ketorolac is a more rapid acting drug in controlling pain caused by renal colic with a similar side effect profile [101].

Pain relief from intramuscular (i.m.) diclofenac compared favourably with those from intravenous (i.v.) ibuprofen and i.v. ketorolac; however, no recommendation can be given due to the manner in which the results have been reported [102]. The addition of antispasmodics to NSAIDs does not result in better pain control. 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 [103,104].

Opioids, particularly pethidine, are associated with a high rate of vomiting compared to NSAIDs and carry a greater likelihood of further analgesia being needed [99,105]. If an opioid is used, it is recommended that it is not pethidine. Data on other types of non-opioid and non-NSAID medication is increasing. Ketamine in combination with morphine, compared to morphine alone, leads to morphine consumption reduction, less pain, nausea and vomiting [106-108]. Patients receiving ketamine and NSAIDs attained greater reduction in pain scores with less side effects, and better functional state, as well as less further analgesia requirement than those administered pethidine [109]. However, when comparing ketamine vs. NSAID (ketorolac) alone, equal efficacy but higher rates of dizziness, agitation and hypertension with ketamine were observed [110]. Conflicting results have been reported regarding the utility of i.v. lidocaine. Acupuncture seems to be effective in renal colic alone or in combination, but there is limited data [111,112].

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 [113,114]. Although diclofenac can affect renal function in patients with already reduced function, it has no functional effect in patients with normal renal function [115].

The systematic review and MA by Hollingsworth et al., [116] 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 [117].

* Maximum single oral dose recommended 1000 mg, total daily dose up to 5000 mg, not recommended in the last three months of pregnancy [118].

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

*** Recommended to counteract recurrent pain after ureteral colic.

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 [119,120].

Only one RCT [121] 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 [119]. 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 an appropriate antibiotic regimen; however, at the cost of longer hospital stay and higher analgesic requirements [122].

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 results. Although clinically well accepted, the impact of a second antibiogram test on treatment outcome has not yet been evaluated. Intensive care might become necessary [123].

3.4.3. Medical expulsive therapy

Several drug classes including α-blockers, calcium channel inhibitors and phosphodiesterase type 5 inhibitors (PDEI-5) are used for MET [124-127]. A class effect of α-blockers in MET has been demonstrated in MAs although this is an off-label indication [128-130]. 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 [131-135]. Based on studies with a limited number of patients [127,128,136,137], no recommendation for the use of PDEI-5 or corticosteroids in combination with α-blockers in MET can be made. The panel concludes that MET using α-blockers seems efficacious in the treatment of patients with distal ureteral stones > 5 mm who are amenable to conservative management. 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-stones 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 and literature reviews [138-140].

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., [141] reviewed the principles and provided guidance to its clinical use, which was supported by Becker, et al., in 2007 [142] and Elsawy et al., in 2019 [143]. Monitoring of radiolucent stones during therapy is the domain of US; however, repeat-NCCT might be necessary [141,142].

In the case of uric acid obstruction of the collecting system, oral chemolysis in combination with urinary drainage is indicated [144]. 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 [144]. Additional shock wave lithotripsy (SWL) might help to improve the results but evidence is weak [145].

3.4.5. Extracorporeal shock wave lithotripsy (ESWL)

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 practiceStenting

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 [146-149].

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 [150].

Shock wave rate

Lowering shock wave frequency from 120 to 60-90 shock waves/min improves SFRs [151-159]. Ultraslow frequency 30 shock waves/min may increase SFR [160]. Tissue damage increases with shock wave frequency [161-164].

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 [165]. Starting SWL on a lower energy setting with stepwise power (and SWL sequence) ramping can achieve vasoconstriction during treatment [161], which prevents renal injury [166-168]. Animal studies [169] and a prospective randomised study [170] 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 [171,172].

There are no conclusive data on the intervals required between repeated SWL sessions. However, clinical experience indicates that repeat sessions are feasible (within one day for ureteral stones) [173].

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 [174]. Ultrasound gel is probably the most widely-used agent available as a lithotripsy coupling agent [175].

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 [176].

Pain Control

Careful control of pain during treatment is necessary to limit pain-induced movements and excessive respiratory excursions [177-180].

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) [67,181,182].

Medical therapy following ESWL

Despite 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 [183-192].

Post-treatment management

Mechanical percussion and diuretic therapy can significantly improve SFRs and accelerate stone passage after SWL [193-196].

Complications of extracorporeal shock wave lithotripsy

Compared to percutaneous nephrolithotomy (PNL) and ureteroscopy (URS), there are fewer overall complications with SWL [197,198] (Table 3.8). 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 [199-205].

Table 3.8: Shock wave lithotripsy-related complications 196-210

3.4.6. Ureteroscopy (retrograde and antegrade)

The current standard for rigid ureteroscopes is a tip diameter of < 8 French (F). Rigid URS can be used for the whole ureter [199]. However, technical improvements, as well as the availability of digital scopes, also favour the use of flexible ureteroscopes in the ureter [221].

Percutaneous antegrade removal of ureteral stones is a consideration in selected cases, i.e., large
(> 15 mm), impacted proximal ureteral calculi in a dilated renal collecting system [222-224], or when the ureter is not amenable to retrograde manipulation [224-228].

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 systematic review addressing renal stones > 2 cm showed a cumulative SFR of 91% with 1.45 procedures/patient; 4.5% of the complications were > Clavien 3 [221,229,230]. Digital scopes demonstrate shorter operation times due to the improvement in image quality [229].

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 [231].

Best clinical practice in ureteroscopyAccess to the upper urinary tract

Most interventions are performed under general anaesthesia, although local or spinal anaesthesia is possible [232]. Intravenous sedation is suitable for female patients with distal ureteral stones [233]. Antegrade URS is an option for large, impacted, proximal ureteral calculi [222-224,234]. Reduction of flexible ureteroscope diameter may provide similar vision, deflection, and manoeuvrability to standard flexible ureteroscopes potentially with improved ureteric access [235]. Disposable ureteroscopes provides similar safety and clinical effectiveness to reusable scopes. Concerns regarding the cost effectiveness remain [236,237].

Safety aspects

Fluoroscopic equipment must be available in the operating room. The Panel recommend placement of a safety wire, even though some groups have demonstrated that URS can be performed without it [238-240]. 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 [241]. Bilateral URS during the same session is feasible resulting in equivalent-to-lower SFRs, but slightly higher overall complication rates (mostly minor, Clavien 1 and 2) [242,243].

Difficult lower pole anatomy such as steep infundibulopelvic angle predisposes to failure during RIRS [244]. Prolonged operative times are linked to increased complication rates in ureteroscopy, and efforts must be made to keep it below 90 minutes [245].

Ureteral access sheaths

Hydrophilic-coated ureteral access sheaths, which are available in different calibres (inner diameter from 9 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, decreases intrarenal pressure, and potentially reduces operating time [246,247].

The insertion of ureteral access sheaths may lead to ureteral damage, the risk is lowest in presented systems [248]. No data on long-term side effects are available [248,249]. Whilst larger cohort series showed no difference in SFRs and ureteral damage (stricture rates of about 1.8%), they did show lower post-operative infectious complications [250,251]. The use of ureteral access sheath is safe and can be useful for large and multiple renal stones or if long procedural time is expected [252].

Stone extraction

The aim of URS is complete stone removal. “Dust and go” strategies should be limited to the treatment of large (renal) stones [253]. Stones can be extracted by endoscopic forceps or baskets. Only baskets made of nitinol can be used for flexible URS [254].

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 [255,256]. Compared to low-power lasers, high-power laser reduces procedural time although the reported difference in clinical outcomes were non-significant [257] (J Pneumatic and US systems can be used with high disintegration efficacy in rigid URS [258,259]). 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 [260]. Medical expulsion therapy following Ho:YAG laser lithotripsy increases SFRs and reduces colic episodes [261]. Thulium fiber laser (TFL) for stone disease has a promising role and offers good clinical outcomes, which seem to be comparable to Ho:YAG laser (holmium) laser. More comparative clinical studies are, however, needed between these two modalities [262,263].

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 [264,265].

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 [266-269]. A ureteral catheter with a shorter indwelling time (one day) may also be used, with similar results [270].

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 one to two weeks after URS. Alpha-blockers reduce the morbidity of ureteral stents and increase tolerability [271,272].

Medical expulsive therapy before and after ureteroscopy

Medical expulsion therapy before URS might reduce the risk for intra-operative ureteral dilatation, protect against ureteral injury and increase stone free rates four weeks after URS [273].

Medical expulsion therapy following Ho:YAG laser lithotripsy accelerates the spontaneous passage of fragments and reduces episodes of colic [261].

Complications of ureteroscopy

The overall complication rate after URS is 9-25% [199,274,275]. Most complications are minor and do not require intervention. There is evidence suggesting a risk of post-operative urosepsis of up to 5% [276,277]. Ureteral avulsion and strictures are rare (< 1%). Previous perforations, pre-operative positive urine cultures and longer operation time are the most important risk factor for complications [245,278]. Infectious complications following URS can be minimised using prophylactic antibiotics, limiting stent dwell and procedural time, identification and treatment of UTI, and planning in patients with large stone burden and multiple comorbidities [279].

High intrarenal pressure (IRP) predisposes to URS complications, and measures should be used to reduce IRP. Currently there are no accurate ways to measure intra-operative IRP [280].

3.4.7. Percutaneous nephrolithotomy

Percutaneous nephrolithotomy 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 reference. 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 [281,282].

Contraindications

Patients receiving anti-coagulant therapy must be monitored carefully pre- and post-operatively. Anti-coagulant therapy must be discontinued before PNL [283].

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 practiceIntracorporeal 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 [284]. 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 interposed organs within the planned percutaneous path (e.g., spleen, liver, large bowel, pleura, and lung).

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 operation time. Prone position offers more options for puncture and is therefore preferred for upper pole or multiple accesses [285,286]. On the other hand, supine position allows simultaneous retrograde access to the collecting system, using flexible ureteroscope (ECIRS) [287].

Puncture

Although fluoroscopy is the most common intra-operative imaging method, the (additional) use of US reduces radiation exposure [288-290]. 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 [289,291,292].

Dilatation

Dilatation of the percutaneous access tract can be achieved using a metallic telescope, single (serial) dilators, or a balloon dilatator. During PNL, safety and effectiveness are similar for different tract dilatation methods [293]. Although there are papers demonstrating that single step dilation is equally effective as other methods and that US only can be used for the dilatation, the difference in outcomes is most likely related to surgeon experience rather than to the technology used [293,294].

Choice of instruments

The Panel performed a systematic review assessing the outcomes of PNL using smaller tract sizes (< 22 F, mini-PNL) for removing renal calculi [282]. 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 tends 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. There is some evidence of using suction during PNL to reduce intra-renal pressure and increase stone free rate [295].

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 [282,296,297]. 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 [298]. In uncomplicated cases, the latter procedure results in a shorter hospital stay, with no disadvantages reported [299].

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% [300].

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 [301,302]. Intra-operative irrigation pressure < 30 mmHg and unobstructed post-operative urinary drainage may be important factors in preventing post-operative sepsis [303]. Bleeding after PNL may be treated by briefly clamping the nephrostomy tube. Super-selective embolic occlusion of the arterial branch may become necessary in the case of severe bleeding.

High intrarenal pressure (IRP) predisposes to PNL complications, and measures should be used to reduce IRP. Currently there are no accurate ways to measure intra-operative intrarenal pressure [280].

3.4.8. General recommendations and precautions for stone removal

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 [304].

Peri-operative antibiotic prophylaxis

For prevention of infection following URS and percutaneous stone removal, no clear-cut evidence exists
[279,305]. 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 [306]. Single dose administration was found to be sufficient [307]. Pre-operative prophylactic antibiotics compared to single dose before anaesthesia significantly reduced post-operative sepsis (OR: 0.31, 95% CI: 0.20–0.50; P < 0.00001) and fever (OR: 0.26, 95% CI: 0.14–0.48; P < 0.0001) [301].

Patients with a bleeding disorder, or receiving antithrombotic therapy, should be referred to an internist for appropriate therapeutic measures before deciding on stone management [308-312]. In patients with an uncontrolled bleeding disorder, 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 [313-315]);
• PNL;
• percutaneous nephrostomy;
• laparoscopic surgery;
• open surgery [308].

Shock wave lithotripsy is feasible and safe after correction of the underlying coagulopathy [316-320]. In the case of an uncontrolled 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 [321-323]. Despite appropriate cessation of anti-platelet agents, following standardised protocols prolonged haematuria in tube drainage after PNL has been reported [324]. Only data on flexible URS are available which support the superiority of URS in the treatment of proximal ureteral stones [325,326]. Although URS is safe in patients with bleeding disorders or anticoagulation, an individualised patient-approach is necessary [323].

Table 3.9: Risk stratification for bleeding [ 310-312,327]

Table 3.10: Suggested strategy for antithrombotic therapy in stone removal [310-312]

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

A high BMI can pose a higher anaesthetic risk and a lower success rate after SWL and PNL and may influence the choice of treatment [328].

Stones composed of brushite, calcium oxalate monohydrate, or cystine are particularly hard, as well as homogeneous stones with a high density on NCCT [45,329]. Percutaneous nephrolithotomy or RIRS and URS are alternatives for removal of large SWL-resistant stones.

Contraindications of extracorporeal SWL

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

• pregnancy, due to the potential effects on the foetus [330];
• bleeding disorders, which should be compensated for at least 24 hours before and 48 hours after treatment [331];
• uncontrolled UTIs;
• severe skeletal malformations and severe obesity, which prevent targeting of the stone;
• arterial aneurysm in the vicinity of the stone [332];
• 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 [323]. Other important contraindications include:

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

General contraindication for endourological procedures

Endourological interventions do not adversely affect renal function although care must be taken in those with poor pre-operative renal function, diabetes and hypertension [333].

3.4.9. Specific stone management of ureteral stones

There are only limited data regarding spontaneous stone passage according to stone size [334]. It is estimated that 95% of stones up to 4 mm pass within 40 days [199].

Based on an analysis of available evidence, an exact cut-off size for stones that are likely to pass spontaneously cannot be provided [199].

Spontaneous stone passage was reported for 49% of upper ureteral stones, 58% of mid ureteral stones and 68% of distal ureteral stones. Considering stone size almost 75% of stones < 5 mm and 62% of stones > 5 mm passed spontaneously, with an average time to stone expulsion about seventeen days (range 6-29 days) [335]. The Panel is aware of the fact that spontaneous stone expulsion decreases with increasing stone size and that there are differences between individual patients.

Sexual intercourse has been reported to be beneficial in facilitating stone expulsion in men with ureteral stones, in one MA consisting of three RCTs [336].

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.

Indications for active removal of ureteral stones are [199,334,337]:

• 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).

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 has been significantly reduced [338]. 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 [339].

The Panel performed a systematic review to assess the benefits and harms of URS compared to SWL [340]. Compared with SWL, URS was associated with a significantly greater SFR of 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 lower morbidity. Clavien-Dindo grade complications were, if reported, less frequent in patients treated with SWL.

Bleeding disorder

Ureteroscopy can be performed in patients with bleeding disorders, with a moderate increase in complications (see also section 3.4.8.2) [323].

*See stratification data [199].

Figure 3.1: Treatment algorithm for ureteral stones (if active stone removal is indicated)

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.

Observation of renal stones, especially in calyces, depends on their natural history (section 3.4.10.3). The recommendations provided are not supported by high-level literature [341]. 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 [342]. In a systematic review of patients with asymptomatic renal stones on active surveillance spontaneous stone passage rates varied from 3-29%, symptom development from 7-77%, stone growth from 5-66%, surgical intervention from 7-26% [341].

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.

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) [343];
• 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 in patients with asymptomatic renal stones seems to be ~10-25% per year, with a cumulative five-year event probability of 48.5% [342,344,345]. A prospective RCT with more than two years 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 [346]. Although some have recommended prophylaxis for these stones to prevent renal colic, haematuria, infection, or stone growth, conflicting data have been reported [345,347,348]. 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 [208,349]. 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 [343,350,351].

For general recommendations and precautions see section 3.4.8.

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 [352-355]. Shock wave lithotripsy achieves good SFRs for stones up to 20 mm, except for those at the lower pole [354,356,357]. Endourology is considered an alternative because of the reduced need for 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 3.2) [197]. 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 [358-360]. However, it may be a first-line option in patients where PNL is not an option or contraindicated.

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 < 1 cm [197,352,353,355,356,360-373].

The following can impair successful stone treatment by SWL [363,374-379]:

• 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 (See section 3.4.5 ESWL) [194,196,380].

If there are negative predictors for SWL, PNL and RIRS might be reasonable alternatives, even for smaller calculi [361]. Retrograde renal surgery seems to have comparable efficacy to SWL [197,353,356,381]. 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 [230,382-384]. However, staged procedures are frequently required.

In complex stone cases, open or laparoscopic approaches are possible alternatives although they are infrequently used.

Figure 3.2: 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 intrarenal 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 [385-390]. 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 [391-397].

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 [398,399]. These more invasive procedures have yielded high SFRs and lower auxiliary procedure rates [223,234,400]. A recent systematic review showed no difference in the post-operative phase for stented or unstented laparoscopic ureterolithotomy [400].

Laparoscopic pyelolithotomy could be offered for solitary stones > 2 cm located in renal pelvis as an alternative to PNL [401]. In addition, in selected cases with an extrarenal and dilated pelvis, RLP can be considered as an alternative management of staghorn calculi [402].

A few studies with limited numbers of patients have reported using robotic surgery in the treatment of urinary stones [403]. Open surgery should be considered as the last treatment option, after all other possibilities have been explored.

Studies on laparoscopy should be interpreted with caution due to their weak design and low quality of evidence.

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 [404]. Steinstrasse occurs in 4-7% cases of SWL [218], and the major factor in the development of steinstrasse formation is stone size [405].

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) suggested a benefit of stenting before SWL in terms of steinstrasse formation, but did not result in a benefit on SFRs or less auxiliary treatments [147]. When steinstrasse is asymptomatic, conservative treatment is an initial option. Medical expulsion therapy increases stone expulsion and reduces the need for endoscopic intervention [406,407]. Ureteroscopy and SWL are effective in treatment of steinstrasse [220,408]. In the event of UTI or fever, the urinary system should be decompressed, preferably by percutaneous nephrostomy [120,122].

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 [349,409,410]. 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. Therefore, imaging at four weeks seems most appropriate [411-413]. 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 [414,415]. However, more than half of the patients with a residual fragment on NCCT images may not experience a stone-related event [416].

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 [417]. 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 [208,418,419]. 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 [409].

3.4.14. Management of specific patient groups

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, spontaneous renal fornix rupture [420] 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 [421-423].

Unfortunately, these temporising therapies are often associated with poor tolerance, and they require multiple exchanges during pregnancy, due to the potential for rapid encrustation [424].

Ureteroscopy has become a reasonable alternative in these situations [413,425]. When compared to temporary ureteral JJ stenting until after delivery, ureteroscopy resulted in fewer needs for stent exchanges, less irritative LUTS and better patient satisfaction [426].

Non-urgent ureteroscopy in pregnant women is best performed during the second trimester by an experienced urologist. Counselling of the patient should include access to neonatal and obstetric services [76].

Although feasible, percutaneous removal of renal stones during pregnancy remains an individual decision and should be performed only in experienced centres [427]. Pregnancy remains an absolute contraindication for SWL.

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 [428,429]. Metabolic factors (hypercalciuria, hyperoxaluria and hypocitraturia), infection with urease-producing bacteria, foreign bodies, mucus secretion, and urinary stasis are responsible for stone formation [430] (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 [431].

Management

Smaller upper-tract stones can be treated effectively with SWL [227,432]. In the majority of cases, endourological techniques are necessary to achieve stone-free status [225]. In individuals with long, tortuous conduits or with invisible ureter orifices, a retrograde endoscopic approach might be difficult or impossible [433].

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 [434].

Before considering any percutaneous approach in these cases, CT should be undertaken to assess the presence of overlying bowel, which could make this approach unsafe [435], and if present, an open surgical approach should be considered.

Prevention

Recurrence risk is high in these patients [431]. 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 [436].

Aetiology, clinical presentation and diagnosis

Patients with neurogenic bladder develop urinary calculi because of additional risk factors such as bacteriuria, hydronephrosis, VUR, renal scarring and lower urinary tract reconstruction [437]. 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 [438,439].

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 [440]. 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 [441]. The risk of stone formation after augmentation cystoplasty in immobile patients with sensory impairment can be significantly reduced by irrigation protocols [436].

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.

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 [442].

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. Stones in kidney allografts have an incidence of 1% [443]. Risk factors for de novo stone formation in these patients are multi-fold:

• 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 [444] are biochemical risk factors.

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 [445-447]. 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 [446,448,449]. Retrograde access to transplanted kidneys is difficult due to the anterior location of the ureteral anastomosis, and ureteral tortuosity [450-452].Treatment of donor stones may be needed pre-transplant and increases the pool available for renal transplants. Post-transplant stone disease may also need treatment to maintain the allograft function. A systematic review evaluating the outcomes of pre- vs. post-transplant URS demonstrated a 100% SFR with an overall 7.5% complication rate, compared to SFR of 60-100% with an overall complication rate of 12.9% for post-transplant URS; most complications were Clavien 1 [453].

Table 3.11: Special problems in stone removal

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 nationwide epidemiological studies, studies performed in different counties worldwide [467] and large-scale databases [468,469] indicate that the incidence and prevalence of paediatric urinary stone disease has increased over the last few decades. Although boys are most commonly affected in the first decade of life [470] the greatest increase in incidence has been seen in older female adolescences [467].

Stone composition is similar in children as in adults, with a predominance of calcium oxalate stones. Compared to historical data, metabolic abnormalities responsible for stone formation are less commonly identified in children nowadays [471-473]. Hypocitraturia, low urine volume and hypercalciuria predominate
[85,471-473]. 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 [473]. Genetic or systemic diseases (e.g., cystinuria or nephrocalcinosis) contributing to stone formation are relatively frequent in children accounting for less than 17% of the identifying causes [471,474]. 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 [475-477].

For diagnostic procedures see section 3.3.3.2, for acute decompression see section 3.4.2. and for metabolic evaluation see chapter 4.

Children with urinary stones can be asymptomatic or present with non-specific symptoms that necessitate a high index of suspicion for proper diagnosis. Symptoms are age-dependent with infants presenting with crying, irritability and vomiting in 40% of cases [478] while in older children flank pain, micro or gross haematuria and recurrent UTIs are more common [479].

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 [480,481] or residual fragments remained after SWL, RIRS or PNL [482]. 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 [480]. Intervention may be needed for stones located elsewhere independently of their size [480-482].

There are limited studies on MET as off-label expulsive therapy for children with stones which show conflicting outcomes. A recent MA of five trials showed that adrenergic α-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) [483]. Similarly, an updated systematic review of six placebo-controlled studies showed that α-blockers might increase SFR of distal ureteric stones (RR: 1.34, 95% CI: 1.16 - 1.54) [484]. 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 [484].

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 [485].

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 [486-490]. A MA of fourteen 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 [485]. 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 [484]. Shock wave lithotripsy is well tolerated; 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 [491].

Based on the results of a recent MA which compared SWL to dissolution therapy for intra-renal 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 [484]. When SWL was compared to mini-percutaneous nephrolithotomy for lower pole renal stones 1-2 cm in size SWL resulted in lower SFRs (RR: 0.88, 95% CI: 0.80 - 0.97; moderate-quality evidence) and higher rates of secondary procedures (RR: 2.50, 95% CI: 1.01 - 6.20; low-quality evidence); however, SWL showed less severe adverse events (RR: 0.13, 95% CI: 0.02 - 0.98; low-quality evidence) [492].

Rigid/semi-rigid ureteroscopy

In recent years ureteroscopy is increasingly used in children with ureteral stones [493]. Ureteroscopy proved to be effective with SFR of 81-98% [494-496], retreatment rates of 6.3%-10% [497] and complication rates of 1.9-23% [494-496,498]. Similar to adults, routine stenting is not necessary before URS. Pre-stenting may facilitate URS, increase SFR and decrease complication rates [499,500].

Flexible ureteroscopy/retrograde intrarenal surgery

Retrograde intra-renal surgery with flexible ureteroscopes (FURS) 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% [501-504]. Younger age, cystine composition [505], large stone diameter [504] and lack of pre-stenting predispose to FURS failure in children [499].

Although high-level evidence is lacking to support a strong recommendation [484], FURS may be a particularly effective treatment option for lower calyceal stones in the presence of unfavourable factors for SWL [496,502,506].

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 [507]. Similarly, retrospectively data indicate that RIRS may achieve lower SFRs compared to minor micropercutaneous surgery in favour of shorter operative time, shorter fluoroscopy time, and less hospitalisation time [508,509]. A recently published MA confirmed these results [510].

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 [507-509,511,512] with an overall complication rate of 20% [513]. High degree of hydronephrosis, increased number of tracts and operative time [514] and large tract size [512,515-517] are associated with increased blood loss. Child age [516] and stone burden [512] 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 [518,519].

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 [520]. Using pre- and post-PNL dimercaptosuccinic acid (DMSA) scans, Cicekbilek et al., demonstrated that PNL tracts between 12-24 Charrière in size did not cause significant harm to paediatric kidneys [511].

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 hospitalised patients (52% aged 15-17 years) who required surgical intervention for urinary stones [521]. 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 > 1 cm single stone located in an extra-renal pelvis [522], or when laparoscopic ureterolithotomy was applied to impacted ureteric stones > 1.5 cm, or to ureteric stones that were refractory to SWL or URS [523]. There are extremely limited data available on efficacy and complications of robot-assisted laparoscopic management of paediatric urolithiasis [524].

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).

3.5. Radiation exposure and protection during endourology

The diagnosis and treatment of nephrolithiasis is associated with high levels of ionising radiation exposure to patients [525,526]. Currently, there are no studies estimating the lifetime radiation exposure of stone formers or the subsequent risk of malignancy development. The radiation exposure of endourologists has been extensively studied. Still, there are no studies assessing the risk of radiation induced malignancies in urologists or operating theatre staff members [527-529].

Current evidence from atomic bomb patients [530,531], retrospective epidemiological data on medical exposure [532,533] and modelling studies [534,535] suggest an age and dose dependent risk of secondary malignancy from ionising radiation.

The International Commission on Radiological Protection (ICRP) recommends a maximum annual occupational exposure of 50mSv [536]. However, the risk of radiation induced malignancy follows a stochastic model having no known safe threshold of exposure. Taking this into consideration as well as the length of a urologists career the upper limit of 50mSv is still highly concerning.

Table 3.12 shows the EAU Urolithiasis guidelines panel recommended protection methods to reduce radiation exposure to patients, surgical, anaesthesiologic and nursing staff.

Table 3.12 Radiation protection measures

Availability of fluoroscopy is mandatory for endourological procedures. There is an increasing interest on fluoroless and fluoroscopy-free operations in urology. Several RCTs have been published showing a good outcome in means of stone-free and complication rates [176,289,537-539]. These trials have been limited to non-complex cases and they were not sufficiently powered to show non-inferiority of fluoroscopy in PNL [289,527] or superiority of US in URS [540,541]