Review Article MANAGEMENT OF RENAL AND URETERIC CALCULI GALVIN and PEARLE

I have put a mini-review into this section this month; this is from one of the leading experts in this eld, and gives an up-to-date overview of the contemporary management of renal and ureteric calculi.

The contemporary management of renal and ureteric calculi

David J. Galvin and Margaret S. Pearle
Department of Urology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
Accepted for publication 13 July 2006

KEYWORDS renal calculi, upper tract stones, ureteroscopy, percutaneous nephrolithotomy, ureteric stones

INTRODUCTION Urinary stone disease is one of mankinds most ancient ailments, currently remaining a common cause for both ofce and emergency room referrals. About one in eight white men will develop a stone within their lifetime, and those who form one have an even chance of recurrence in the subsequent 510-year period [1]. Males and those with a family history of stone disease are three times more likely to be aficted than others. Whether the gender difference is intrinsic or diet-related is not entirely clear, but there is mounting evidence that the difference between the genders gap might be diminishing [2]. Men appear to excrete more oxalate in their urine and women more citrate (thus protecting against stone formation), which might explain, in part, the gender difference. Residents in more afuent Western countries who consume more animal protein are also at higher risk of stone formation. Over the last 20 years signicant advances have been made in the management of upper urinary tract calculous disease, with the advent of ESWL and the development of small-calibre endoscopes that allow access to the entire urinary tract with little or no effect on renal function. Consequently,

open surgery has been relegated to a rare, salvage procedure. The understanding of the pathogenesis of stone disease has also progressed, and has led to prophylactic dietary measures and medications to prevent stone recurrence. Most stone-formers can now be offered prophylactic measures, if not denitive treatment, for their recurrent stone disease. This review of the current management of upper tract stone disease attempts to consolidate the surgical options available, based on published evidence.

RENAL CALCULI EXPECTANT MANAGEMENT Glowacki et al. [3] examined the natural history of asymptomatic calyceal renal calculi in 107 patients who were observed for a mean of 32 months. All patients remained asymptomatic during the initial 6 months, but 32% of them had an episode of ureteric colic in the subsequent 2 years, with half requiring surgery. Overall, Glowacki et al. identied a 50% risk of having a symptomatic event within 5 years of diagnosis; the likelihood of an event correlated with the number of stones. Similarly, Hubner et al. [4] followed 80 renal stones in 63 patients for 7 years, reporting that 40% of patients required surgery. Half of the stones grew during the period of observation and 68% of patients became symptomatic, suggesting that early intervention might be desirable, particularly as the morbidity associated with ESWL is low. Before the advent of endourological

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techniques and ESWL, removing asymptomatic calyceal calculi was not practical. However, with noninvasive and minimally invasive treatments available, the treatment of renal calculi has become a more attractive option for the patient who wants the stone removed. Staghorn calculi, if managed conservatively, are associated with eventual renal destruction and signicant morbidity and mortality rates [5]. As such, the AUA Nephrolithiasis Clinical Guidelines Panel strongly recommended the active treatment of staghorn calculi [6]. The decision to treat unobstructing, asymptomatic renal calculi can be left to the discretion of the patient and physician. However, conservative management should be accompanied by a metabolic evaluation and medical treatment to prevent stone growth or stone recurrence.

on these ndings, Lingeman convened a multicentre lower-pole study group (Lower pole study 1) to prospectively compare ESWL and PCNL for treating lower-pole stones in a randomized trial [10]. The stone-free rates for PCNL were greater than for ESWL (95% vs 37%), and stone-free rates for ESWL were only acceptable for stones of <10 mm (63%) while stone-free rates were uniformly high with PCNL regardless of stone size (86100%). The second study examined the roles of ESWL and ureteroscopy in managing lower-pole calculi of <10 mm [11]. Whereas ESWL had a poorer stone-free rate at 3 months (35% vs 50%), it was more acceptable to patients and had fewer complications. ESWL can be recommended to patients as rst-line therapy in the management of lower-pole calyceal stones of <10 mm. Recognizing the limitations of ESWL for lower-pole stones, several investigators described measures to improve the clearance of fragments from the lower pole, e.g. a regimen of hydration, inversion, diuresis or placing a retrograde or percutaneous catheter directed into the lower pole to ush fragments from the lower-pole calyces during ESWL. Sampaio and Aragao [12] rst described three anatomical factors that inuence the success of fragment clearance after ESWL, including an infundibulopelvic angle of >90, an infundibular width of >4 mm and the special arrangement of the lower pole calyceal group. Since then several investigators correlated lower-pole calyceal anatomy with stone-free rates after ESWL, but not all agree on which factors are important or on the particular threshold for each of the anatomical factors. Indeed, some investigators have failed to identify any association between calyceal anatomy and stone clearance after ESWL [13]. Although stone composition cannot be reliably predicted by CT, Hounseld density (HU) and skin-to-stone distance (as a surrogate for BMI) can be used to predict ESWL success rates. Pareek et al. [14] evaluated 64 patients with lower-pole calculi of 515 mm and found a statistically signicant association between the stonefree rate, stone density and BMI (measured as skin-to-stone distance on CT). The most powerful predictor of failure was a skin-tostone distance of >8 cm. PCNL is a highly effective treatment for renal calculi, but is associated with greater

morbidity than either ESWL or ureteroscopy. As such, PCNL should be considered in patients with a large or complex stone burden (stones of >2 cm), or for those with lowerpole calculi of >10 mm, due to the poor outcome with ESWL. Outcomes for PCNL are relatively independent of stone size and uniformly high for stones in all locations. Specically, the AUA Nephrolithiasis Clinical Guidelines Panel on Staghorn Calculi concluded that ESWL monotherapy is not recommended as a rst-line treatment for staghorn calculi (especially cystine stones), and that ESWL should only be used in combination with PCNL, the PCNL being performed after ESWL [15]. PCNL can also be used as a monotherapy, and adverse events in all groups are similar.

URETEROSCOPY Advances in exible ureteroscopes and the introduction of the holmium:YAG laser have made ureteroscopy an alternative to ESWL and PCNL for treating renal calculi. The advent of rigid and semi-rigid ureteroscopy just 20 years ago allowed access and visualization of the renal pelvis, and currently exible ureteroscopy permits detailed calyceal examination and therapeutic interventions. Flexible ureteroscopy is limited by the narrowness of both the irrigation and the working channels, and the limited deection traditionally offered, although newer instruments are gradually overcoming these obstacles. The introduction of holmium laser lithotripsy now allows for the fragmentation of all stone types, converting them to dustlike particles, negating the need for fragment removal. Ureteroscopy offers the low morbidity of ESWL but the potential for stone-free rates approaching those of PCNL for small to moderate-sized renal calculi. Fabrizio et al. [16] reviewed their experience with ureteroscopy in the management of renal calculi in 100 patients; they achieved a 77% stone-free rate at 1 month and an overall success rate of 98%, comparing favourably with ESWL. Outcomes were best for stones of <10 mm; only 20% of patients with stones of <10 mm had residual fragments, whereas half of patients with stones of >16 mm had residual fragments. There were no intraoperative complications and 3% had a complication after treatment. Stones in the lower pole of the kidney present a challenge not only for ESWL but also for

ESWL AND PERCUTANEOUS NEPHROLITHOTOMY (PCNL) ESWL has traditionally constituted the favoured approach for small to moderate sized intrarenal calculi, although ureteroscopy has assumed an increasing role in recent years. The highest stone-free rates (8088%) were achieved with ESWL to calculi in the renal pelvis and the PUJ. Success rates are lower in the upper- (73%), middle- (69%) and lower- (63%) pole calyces. Other factors, including stone size, pelvicalyceal anatomy and stone composition, as well as patient characteristics (e.g. body mass index, BMI) all inuence the outcome. Multivariate analysis studies repeatedly conrmed the signicant role of stone size (<2 cm), stone location and stone number, with stone-free status [7,8]. Ackermann et al. [7] evaluated 210 patients who had ESWL monotherapy, among whom 67% were stone-free at 3 months, and found that the BMI and stone number signicantly inuenced the outcome. Stone composition also inuences stone-free rates because different stone types respond differently to shock-waves. Cystine and whewellite (calcium oxalate monohydrate) stones are relatively shock-wave resistant, while whedellite (calcium oxalate dihydrate) responds well to ESWL. Stone fragments in the lower pole of the kidney clear poorly from the more dependent calyces. Lingeman et al. [9] rst recognized the unique and negative impact of a lower-pole location on outcomes in a metaanalysis of PCNL vs ESWL, in which PCNL was associated with signicantly higher stonefree rates than ESWL for all stone sizes. Based

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ureteroscopy. The lower pole of the kidney is the most difcult part of the kidney to access, although with new exible ureteroscopes the lower-pole calyces can be accessed in 93% of cases [17]. In a second lower-pole randomized trial comparing ureteroscopy and ESWL for treating lower-pole stones of <10 mm, both methods were associated with disappointingly low stone-free rates, and although ureteroscopy was associated with higher stone-free rates than ESWL, the differences were not statistically signicantly [11]. Whereas ureteroscopy produced higher stone-free rates and fewer procedures per patient, the patient preference was higher for ESWL and was associated with a reduced convalescence time. Other factors such as stone density, the patients BMI, previous ESWL and lower-pole anatomy might favour ureteroscopy in certain cases. Other specic circumstances where ureteroscopy might be useful is in the management of stones in a calyceal diverticulum or in a horseshoe kidney, where stone-free rates with ESWL are typically low due to poor fragment clearance [18].

URETERIC CALCULI EXPECTANT MANAGEMENT The ability to reliably predict spontaneous stone passage avoids unnecessary surgical intervention. The two most important predictors of stone passage are stone size and location. In a retrospective meta-analysis involving 2704 patients, Hubner et al. [20] determined that the rate of spontaneous stone passage for calculi of <4 mm is 38%, and for calculi of >6 mm is 1.2%. Two-thirds of all stones that passed had done so by 4 weeks. Spontaneous passage of distal ureteric calculi occurred in 45%, middle ureteric calculi in 22% and proximal ureteric calculi in 12% of cases. Smaller prospective series showed higher spontaneous passage rates of 95% for stones of <4 mm and up to half for stones of >5 mm [21]. The use of pharmacological therapy in promoting stone passage has been examined. Porpiglia et al. [22] were able to double the rate of spontaneous passage of distal ureteric stones (mean stone size 5 mm) using prednisolone (30 mg daily for 10 days) combined with either nifedipine (30 mg) or tamsulosin (400 g) for 28 days. There was also a reduction in the time to stone passage, and a reduction in analgesic use. Yilmaz et al. [23] reported a 50% improvement in distal ureteric stone passage in patients treated with -adrenergic blockers compared to a control group. There was no difference in passage rates among the three -blockers examined. Although the efcacy of tamsulosin alone is reported, the use of tamsulosin combined with a corticosteroidal agent was shown to be associated with a slightly shorter time to stone passage, and should be considered best practice in the pharmacological management of distal ureteric calculi of <10 mm in appropriate patients [24,25]. Their use in more proximal stones has yet to be determined. Articial neural networks have also been used to predict stone passage, with a high degree of accuracy; they indicated that the duration of symptoms and the degree of hydronephrosis also compromises stone passage [26]. ESWL ESWL is a convenient, noninvasive, outpatient procedure used to fragment and ultimately clear urinary calculi. Its use in women of reproductive age is controversial, although no

fetotoxic effect has been conrmed [27]. Stone size, location and consistency determine the success of ESWL for ureteric calculi. Pace et al. [28] reported that after one session of ESWL, the stone-free rate for ureteric calculi of >10 mm was 43%, and for stones of <10 mm was 74%. This compares to 93% for ureteroscopy [29]. A second ESWL session for initial treatment failures in the >10 mm group yielded a 37% stone-free rate. ESWL is not a rst-line treatment for stones >10 mm where ureteroscopy is available. Stone location is also a factor inuencing the success of ESWL for ureteric calculi. Success rates for proximal ureteric calculi are 8288% when treated with ESWL [30,31]. No improvement in stone-free rates has been shown with the use of stenting or push-back of stones, although in one study, stenting before ESWL reduced the number of emergency room visits after ESWL for proximal ureteric calculi [32]. The role of ESWL for managing mid-ureteric calculi is less denite. Although stone-free rates are comparable to ureteroscopy (92%), retreatment and complication rates are high [33]. Interestingly, several studies consistently show superior stone-free rates when a stent is inserted before ESWL for mid-ureteric stones [31]. ESWL treatment of distal ureteric stones is associated with high success rates and low complication rates. However, the optimum treatment selection for distal ureteric stones is controversial because of the high success rates of ureteroscopy. Pearle et al. [11] randomized 64 patients with distal ureteric calculi of <15 mm to ESWL or ureteroscopy, and reported complete stone-free rates in both groups, but ESWL had a higher complication rate and cost, while ureteroscopy took longer and was less satisfactory to the patient. Peschel et al. [34] also reported a randomized trial comparing ESWL and ureteroscopy for distal ureteric calculi, and concluded that ureteroscopy was better than ESWL for distal ureteric calculi because it was associated with a shorter time to stone clearance. Stone composition affects the outcome of ESWL for ureteric stones, as with renal stones. Unfortunately, stone composition is rarely known in advance of the procedure. Very hard and very soft stones do not fragment into small fragments suitable for spontaneous passage. ESWL, when used as a monotherapy in the treatment of cysteine, struvite

OPEN SURGERY Open surgery for renal calculi is rapidly disappearing, comprising 0.34% of all stone surgery cases. According to the Urologic Diseases of America Project, rates of open surgery among commercially insured individuals decreased by half between 1992 and 2000 [11]. Because of the high stone-free rates achieved with less-invasive treatments, open surgery is reserved for only the most complex stones and those with altered renal anatomy. Interestingly, few series have compared the outcome of PCNL and open surgery for treating large or complex renal calculi. Brannen et al. [19] compared the outcome of 250 patients with renal calculi treated by PCNL and 100 treated by open surgery for renal calculi, and found that the PCNL group had a shorter hospital stay, required fewer narcotics and recovered faster than those in the open surgery group. PCNL is also more costeffective. Open surgery is indicated with multiple infundibular stenoses requiring substantial reconstruction, a complex stone that could not be removed with an acceptable number of percutaneous procedures, or if a concomitant procedure is required (e.g. pyeloplasty or partial nephrectomy).

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FIG. 1. The optimal therapy for a, renal stones and b, ureteric stones. a

Symptomatic Renal Stone

<2 cm

>2 cm or Staghorn

<1 cm

>1 cm

Non-Lower Pole

Lower Pole

Non-Lower Pole

Lower Pole

Low HU Density Children

High HU Density Cystine or SSD

SWL

Ureteroscopy

PCNL

Proximal

Middle

Distal

<10 mm >10 mm

<10 mm >10 mm

<10 mm >10 mm

In Situ SWL Ureteroscopy

Ureteroscopy or SWL Ureteroscopy

Ureteroscopy or SWL Ureteroscopy

In Females Cystine, HU > 1000: Ureteroscopy Ureteroscopy

In Females

Ureteroscopy

(infective) or calcium oxalate monohydrate calculi, does not perform well and additional procedures are often required [35]. The HU derived from unenhanced CT, an indirect indicator of stone composition, can be used to predict ESWL outcomes. Gupta et al. [36] related the outcome from ESWL with stone density measured in HU on non-contrast CT, and concluded

that patients with dense calculi (>750 HU) required more treatment sessions and were less likely to achieve complete stone clearance than those with calculi with lower HU. URETEROSCOPY Technological improvements, including smaller, exible ureteroscopes and laser

technology, combined with improvements in surgical technique, have further enhanced the successful outcome of ureteroscopy for managing ureteric calculi. In a contemporary review of 598 ureteroscopies for proximal, mid- and distal ureteric calculi, the stonefree rates were 97%, 100% and 98% [37]. Complications, secondary procedures and ureteric stricture rates were low. Overall,

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major complications associated with ureteroscopy are rare and include ureteric avulsion, intussusception, and postoperative infection or steinstrasse [38]. Stricture formation, secondary to either stone impaction or iatrogenic trauma, is currently less common (<1%). Schuster et al. [39] reported an association between the risk of perforation and increased operative time. Minor complications are uncommon and include perforation (1.6%), urinary extravasation, false passage, mucosal abrasion (3.7%), bleeding (<1%), and ureteric obstruction. The routine use of stents after ureteroscopy has recently been questioned, and numerous randomized trials show that selected patients undergoing uncomplicated ureteroscopy can be safely left unstented [40]. In addition, ureteroscopy is a less costly treatment than ESWL for stones in all locations in the ureter [41]. LAPAROSCOPY Raboy et al. [42] rst described successful transperitoneal laparoscopic ureterolithotomy in 1992, and since then many reports have veried the safety and efcacy of the procedure. Laparoscopic procedures are useful in the rare ureteric calculi that cannot be removed by ESWL, ureteroscopy or PCNL, or accessed in any other way, in the presence of an anatomical abnormality or when a concomitant procedure is to be performed. Gaur et al. [43] treated 93 patients using the retroperitoneal route and concluded that laparoscopic ureterolithotomy is an effective and safe alternative in refractory cases. OPEN SURGERY

hyperuricosuria (57%), low urinary citrate (57%), excessive urinary uric acid (40%), excessive urinary calcium or oxalate (39%), hyperoxaluria, and a low urinary pH. 3 These metabolic abnormalities, and the risk of stone formation, were signicantly reduced after 7 days on a balanced diet [46]. Metabolic abnormalities that increase the risk of stones can be identied and treated in up to 95% of recurrent stone-formers [47]. The vast majority of stone-formers require simple dietary or lifestyle modications, and just 15% require pharmacotherapy. Lotan et al. [48] used a decision-tree analysis to evaluate the cost-effectiveness of stone-prevention therapy in both rst-time and recurrent stone-formers. Although effective in reducing stone recurrence, drug therapy was costeffective only in recurrent stone-formers, in whom the rate of recurrence is sufciently high and the cost of the medication is sufciently low. These authors recommended simple medical evaluation and management in recurrent stone-formers. SUMMARY 8 Contemporary stone management should be based on treatment algorithms derived from outcomes, now strongly evidence-based. Figure 1(a,b) presents algorithms for managing both renal (a) and ureteric (b) calculi. As urinary stone disease is common and often recurrent, the application of such algorithms, combined with stone prophylaxis measures, should minimize patient morbidity and hospital attendance, obviate open surgery and preserve renal function in an acceptable and minimally invasive manner. ACKNOWLEDGEMENTS

10

Open ureterolithotomy is rarely indicated in the modern endourological setting, as virtually all ureteric calculi are amenable to minimally invasive therapy [44]. One recent report of open surgery detailed the mini-access ureterolithotomy in 111 patients with refractory ureteric calculi [45]. PREVENTATIVE MEASURES

D.J.G. acknowledges the support of the Royal College of Surgeons in Ireland and Ipsen Pharmaceutical, who supported this work through the Ipsen/RCSI Anthony Walsh Travelling Fellowship. CONFLICT OF INTEREST

11

12 None declared.

Despite the ease with which stones can now be approached surgically, medical prophylactic measures are still recommended to prevent stone recurrence. The most common abnormalities associated with recurrent stone formation are low urine volume, hypercalciuria, hypocitraturia,

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Correspondence: David Galvin, Urology Specialist Registrar, Department of Urology, Mater Misericordiae Hospital, Eccles Street, Dublin 7, Ireland. e-mail: davidgalvin@mac.com Abbreviations: BMI, body mass index; PCNL, percutaneous nephrolithotomy; HU, Hounseld unit.

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