Patients with neurogenic bladder dysfunction as a result

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1 JOURNAL OF ENDOUROLOGY Volume 26, Number 8, August 2012 ª Mary Ann Liebert, Inc. Pp DOI: /end Reviews in Endourology Renal Stone Disease in Spinal-Cord Injured Patients Blayne Welk, M.D., M.Sc., Andrew Fuller, M.D., Hassan Razvi, M.D., and John Denstedt, M.D. Abstract Renal stone disease is common among patients with spinal cord injury (SCI). They frequently have recurrent stones, staghorn calculi, and bilateral stone disease. The potential risk factors for stones in the SCI population are lesion level, bladder management strategy, specific metabolic changes, and frequent urinary tract infections. There has been a reduction in struvite stones among these patients, likely as a result of advances in their urologic care. The clinical presentation of stone disease in patients with SCI may involve frequent urinary infections or urosepsis, and at the time of presentation patients may need emergency renal drainage. The proportion of patients who have their stones treated with different modalities is largely unknown. Shockwave lithotripsy (SWL) is commonly used to manage stones in patients with SCI, and there have been reports of stone-free rates of 50% to 70%. The literature suggests that the morbidity associated with percutaneous nephrolithotomy in these patients is considerable. Ureteroscopy is a common modality used in the general population to treat patients with upper tract stone disease. Traditional limitations of this procedure in patients with SCI have likely been overcome with new flexible scopes; however, the medical literature has not specifically reported on its use among patients with SCI. Introduction Patients with neurogenic bladder dysfunction as a result of spinal cord injury (SCI) need lifelong urologic follow-up. Bladder dysfunction can result from detrusor hypocompliance, detrusor-sphincter dyssynergia, and neurogenic detrusor overactivity. These changes in bladder function can lead to urinary tract infection (UTI), stone disease, bladder cancer, autonomic dysreflexia, and renal dysfunction. 1 The objective of this article is to review the literature on the epidemiology, etiology, presentation, morbidity, and surgical management of upper tract stone disease in patients with SCI. Epidemiology of Renal Calculi The risk of upper tract stone disease in patients with SCI is significantly higher than the general population. 2 5 The lifetime risk for urolithiasis in the general population is estimated at 12% for men and 6% for women 6 ; age standardized annual incidence rates are 0.36 to 1.22/1000 person-years. 2 Several publications have reported on the frequency and rates of renal calculi in the SCI population (Table 1). There is a great deal of variability because of the changes over time in the detection and management of stone disease, the calculation method, and the follow-up period. A large series from the National Spinal Cord Injury Statistical Center (NSCISC) found the incidence rate after the first year post-sci was 8/ 1000 person-years 2 and 9/1000 person-years within their own center in Alabama. 7 One of the studies with the longest follow-up period of 45 years found the cumulative proportion of patients with SCI who had renal calculi was 38%. 5 McKinley and associates 8 found a smaller proportion of patients with SCI had upper tract stones: 1.9% among 3581 patients after 5 years, and 9.4% among 174 patients at 20 years. The incidence of renal calculi appears to peak during the period immediately after SCI. Two series found an increased prevalence during the first 3 months postinjury (31/1000 person-years 2 and 55/1000 person-years 7 ), and a Danish cohort of SCI patients found the highest hazard rate was in the first 6 months postinjury. 5 This early risk of stone formation is hypothesized to be a result of a significantly increased calcium excretion 9 because of immobilization and loss of calcium from the lower extremity skeleton. 10 It was expected that advances in the urologic care of patients with SCI (clean intermittent catheterization, better treatment of urinary infections, and creation of specialized rehabilitation hospitals) would have decreased the rate of stone disease over time. Chen and colleagues, 2 however, demonstrated that the rate of stones in patients injured from 1986 to 1999 vs those injured in 1973 to 1982 was not significantly different. 2 The authors thought that perhaps the decrease in stone episodes was masked by more complete case ascertainment within the NSCISC. The frequency of recurrent stone disease is high in patients with SCI, with reported frequencies of 64%, 4 43%, 11 and 35% 7 within 5 years. This risk appears to be similar or greater than the general population, and repeat stones tend to occur > 1 year after the patient was rendered stone free. 7 Donnellan and The University of Western Ontario, London, Ontario, Canada. 954

2 RENAL STONE DISEASE IN SPINAL-CORD INJURED PATIENTS 955 Table 1. Estimated Incidence of Upper Tract Stones in SCI Patients Series date Population Number SCI patients Proportion of upper tract calculi Mean follow up DeVivo USA % at 8 years NR Kohli USA % NR DeVivo USA % NR Hall USA % NR Jackson USA % NR McKinley USA NR 10.8% NR Donnellan Australia % 21 years Chen USA % at 10 years 7 years Ku Korea % 29 years Ku Korea % NR Hansen Denmark % 24 years SCI = spinal cord injury; NR = not reported; USA = United States of America. Bolton 4 reported 30% of patients with SCI had partial or complete staghorn calculi. These stones are associated with the risk of renal failure, kidney loss, and mortality, especially if untreated. 12 Patients with SCI also have a high incidence of bilateral stones (23% 74% 11,13,14 ). Risk Factors for Renal Calculi in Patients with SCI There are several risk factors among patients with SCI that may account for the increased incidence of upper tract stone disease (Table 2). There are contradictory data about lesion level and completeness: Two series demonstrated that quadriplegic patients with SCI who had complete lesions have the highest risk of renal calculi 8,15 ; however, other studies have failed to demonstrate this link. 16,17 These conflicting results are not surprising given the number of confounding variables (such as length of follow-up, method of bladder management, and number of UTIs). UTI is associated with renal stones in patients with SCI. 15 Urease-producing bacteria are more likely to be present in patients with SCI and renal stones compared with other types of bacteria. 3 This suggests a direct link between infection and stone formation in these patients. Kohli and Lamid 17 demonstrated a higher rate of sepsis and positive urine cultures in patients with SCI who had stone disease. Upper tract stones are predominantly composed of either struvite (magnesium ammonium phosphate), which is the direct result of urinary infection with urease-producing bacteria (such as Proteus, Klebsiella, orpseudomonas) or calcium phosphate, which can Table 2. Common Metabolic Changes and Other Associated Risk Factors Related to Stone Disease Among Patients with Spinal Cord Injury Metabolic factors Hypercalciuria Hypocitraturia Dehydration Increased urinary ph Other factors Urinary tract infection Environmental factors High spinal cord lesion* Complete spinal cord lesion* Indwelling catheter* Bladder calculi* Vesicoureteral reflex* *The relationship between stone risk and these factors is unclear; some may be an association as opposed to a causal relationship. occur as a result of the alkaline ph of infected urine. 14 In the 1970s, > 90% of stones in patients with SCI were reported to be struvite. 18,19 This was an important finding because struvite stones are associated with a propensity to form staghorn calculi, cause renal failure, and present with urosepsis. 12 Acetohydroxamic acid is an oral medication that inhibits bacterial urease and can be used in the management of struvite stones. In a randomized trial of patients with SCI, it did reduce stone growth initially compared with patients receiving placebo, but long-term results were less effective, and 62% of patients discontinued therapy because of side effects. 20 Contemporary series have suggested that the proportion of struvite stones has decreased and that stones of a metabolic origin now predominate in the patient with SCI. 14 A recent study of patients with musculoskeletal anomalies undergoing percutaneous nephrolithotomy (PCNL) found struvite stones in only 18% of patients (compared with 6% in the comparison group). The most common stone type was calcium apatite (50%), which is an uncommon stone in the general population. 21 The shift from an infectious to a metabolic etiology may represent reduced UTI risk among patients with SCI because of dedicated spinal cord injury units, clean intermittent catheterization, bladder augmentation techniques and urodynamic assessment. 21 Several metabolic changes are found in patients with SCI that predispose to stone formation. They have increased urinary calcium, reduced urinary citrate, increased urinary specific gravity, and a high urinary ph. 22 Hypercalciuria is a result of immobilization, 9 and hypocitrituria appears to be from a reduced filtered load of citrate. 23 Oral citrate supplementation may help reduce urinary calcium but may also lead to an undesirable increase in urinary ph; oral citrate supplementation has been studied for catheter encrustation, but not specifically for renal stone prevention in patients with SCI. 22 Dehydration may be a result of hyperhydrosis, reduced fluid intake to reduce catheterizations, or postural oliguria from autonomic disturbances. Interestingly, despite a high urine specific gravity being correlated with stone risk in patients with SCI, 24 increased fluid intake (one of the most common recommendations for all patients with upper tract stones) did not significantly reduce stone formation in one study. 25 After evaluating 24-hour urine collections in a series of patients with musculoskeletal anomalies, Gnessin and coworkers 21 demonstrated a significantly higher urinary ph relative to control patients, 21 perhaps as a result of bacterial infection.

3 956 WELK ET AL. This may account for the higher frequency of calcium phosphate stones seen in this population. Other risk factors for upper tract calculi include bladder catheterization, bladder calculi, vesicoureteral reflux (VUR), and environmental factors. With long-term use, an indwelling Foley catheter has been shown to be associated with renal stones by some investigators 4,26 28 and not associated with renal stones by others. 3,5,16,17 It seems likely that the increased risk of UTI that is related to the use of a Foley catheter is a confounder in these series and may explain the discordant findings. Studies have suggested that bladder calculi 3,15 and VUR 4,27 are risk factors for upper tract stones in patients with SCI; however, some studies have not shown this relationship with bladder calculi 27 or VUR. 16,17 Environmental factors (such as temperature) play a role in the risk of stone formation in patients with SCI and exert a greater magnitude of risk than they do in the general population. 29 Clinical Presentation The initial presentation of patients with stone disease is unique and often serious in those with SCI. Depending on the level of their neurologic dysfunction, many patients do not experience flank pain. The most common presentation among patients with SCI was urinary infection and sepsis 11,17 or frequent urinary infections. 4 Autonomic dysreflexia can also be a rare presentation of upper tract stone disease. 30 If a stone is obstructing the kidney in the setting of infection, emergent renal drainage is necessary (which occurred in 13% 17% of patients 4,11 )andcan precipitate pyonephrosis (which was present in 19% of stone episodes 4 ). Vaidyanathan and associates 31 described a series of four patients with SCI in whom the diagnosis of obstructive calculi was missed until abdominal imaging was performed. Annual screening ultrasonographies are recommended to detect asymptomatic stone disease. 5,11,13,31,32 Stone-Related Morbidity The specific morbidity and mortality of stone disease includes the initial presentation of the stone, the required surgical treatment, and the patient s long-term renal function. Stone-related morbidity is compounded by impaired respiratory function, poor healing, and the chronic bacterial colonization found in patients with SCI. Stone disease has been associated with impaired renal function in patients with SCI, 24,33 and is reported to occur in 28% to 32% of patients, although no patients reached end stage renal failure after a mean of 29 years of follow-up. 4,16 Chen and colleagues 7 failed to demonstrate a significant change in renal function within 7 years of follow-up of the initial stone episode, although there was a trend toward decreased renal function in those with recurrent or residual stones. If the diagnosis of obstructive renal calculi is missed altogether, this can lead to renal loss. 31 In two series, death occurred at presentation or shortly after treatment in 7% 34 and 10% 4 of patients. Treatment of Upper Tract Calculi in Patients with SCI The management of upper tract stones is more difficult in patients with SCI than in the general population. The higher incidence of bacteriuria and struvite stones increases the risk of sepsis either with the presentation of the stone or as a result of treatment of the stone. 17 Treatment of sepsis is complicated by the high rate of multidrug-resistant bacteria within this population. 35 Limb contractures and spinal curvature make specific positioning for retrograde ureteroscopy and certain shockwave lithotripsy (SWL) machines difficult. The use of fluoroscopy to localize the stone can be compromised by metallic implants. Technologic advances, such as small flexible ureteroscopes and newer SWL machines, have reduced the impact of these previous limitations. There is little literature concerning the most common treatment modalities used among patients with SCI who have upper tract stones. The series by Donnellan and Bolton 4 of patients needing treatment 4 used primarily PCNL (53%), open stone surgery (24%, which was before 1995), and SWL (15%) to manage struvite stones. The series by Chen and colleagues 7 of patients presenting with renal stones found the majority of stones were managed conservatively (68%), or with PCNL (16%) or SWL (8%). As with any form of surgical management, definitive treatment in the SCI population should be achieved in a manner that minimizes invasiveness and morbidity. Successful treatment depends on a range of factors including careful preoperative planning and the availability of specialized instrumentation and imaging. Cases will necessitate improvization and the ability to apply a range of techniques to achieve a successful outcome. Urine culture and sensitivities should be obtained preoperatively in all patients to allow appropriate antibiotic treatment to prevent urosepsis. 36 In cases in which a urinary diversion has been performed, one must thoroughly understand the nature of the diversion. Likewise, altered anatomic relations after reconstructive surgery such as bladder augmentation can make retrograde access to the ureter challenging, although studies have demonstrated that retrograde endourologic techniques are feasible and safe, with success rates of 75%. 37 The least invasive treatment modality for upper tract stones is SWL. Series that look specifically at patients with SCI have shown post-treatment stone-free rates of 50% to 73%. 4,38 44 Poor stone-free rates in this population may be from reduced clearance of fragments because of impaired peristalsis from urinary infection, 41 the often large stone burden, and the reduced mobility of patients with SCI. In patients without SCI, inversion, diuresis, and flank percussion improve the passage of stone fragments after SWL 45 ; however, this technique has not been studied in patients with SCI. Some authors report that complete quadriplegics can be treated with minimal anesthesia; however, they must be monitored for autonomic dysreflexia. 44 SWL is usually performed as an outpatient procedure, and significant complications are rare in these series. Patients with SCI often need ureteral stents or percutaneous nephrostomy tubes before SWL 39,41 because of the stone burden or infection. It is important to render the patient stone free, even if multiple treatments are needed, because retained fragments of struvite stones can lead to stone recurrence 43 and are a potential source for future infection. 38 There remain no published data on the outcomes of ureteroscopy in the SCI population. When ureteroscopy is contemplated, a careful preoperative assessment of musculoskeletal deformities is essential to ensure that the patient can be positioned to allow access to the urethra. In those patients in whom retrograde access cannot be achieved, a

4 RENAL STONE DISEASE IN SPINAL-CORD INJURED PATIENTS 957 percutaneous approach may be useful to perform antegrade flexible ureteroscopy and lithotripsy. 32 PCNL is generally indicated in patients with SCI who have renal stones 2 cm, or if other treatment options are not possible. The standard technique of percutaneous access has been well described and involves puncture of the collecting system under fluoroscopic guidance, balloon or sequential dilation, and placement of a working sheath. 46 A percutaneousapproachallowsaccesstotherenalpelvisandureter, which may not otherwise be possible because of urinary diversions or limb contractures. Although the majority of PCNL procedures are performed with the patient in the prone position, the supine technique may be useful in some cases of SCI when prone positioning is not possible because of musculoskeletal deformity. In the context of lower limb contractures and/or previous reconstructive surgery, ureteral access to allow retrograde injection of contrast media for a fluoroscopy-guided puncture may not be possible, and image guided puncture with ultrasonography or CT may be used as an alternative. One should confirm placement of the tube at the tip of a posteriorly oriented calix before tract dilation to minimize the likelihood of segmental arterial injury (especially if access has been placed by image guidance). When the location of percutaneous renal access is deemed inadequate, one should have a low threshold to repuncture in a more suitable location. Access via an upper pole calix often provides optimal access to the ureter, although the benefit of such access needs to be balanced against the higher risk of pulmonary complications. PCNL requires general anesthesia and has been reported to be associated with a hospital stay of 7 to13 days. 11,34 Admission to an intensive care unit may be needed. Culkin and coworkers 47 described a series of 35 patients with SCI who had a 20% frequency of significant complications (death related to sepsis, perirenal abscess, hydrothorax, aspiration pneumonia, respiratory arrest, and nephrocolonic fistula) and a 49% transfusion rate. Rubenstein 11 reported on 23 patients with neurogenic bladder and similarly reported significant morbidity in 15% of procedures (urosepsis, abscess, fistula, and hydrothorax). The series by Lawrentschuk and associates 13 of 26 patients with SCI had a 12% serious complication rate (pneumothorax and urosepsis). The series by Matlaga and colleagues 14 of 32 patients (both spina bifida and SCI) reported minimal complications, more in keeping with the use of the procedure in the general population. Minor complications are common, and include postoperative fever, tube dislodgement, and transfusion. 11,13,34,47 Stone-free rates from these four series were 86% to 98% (similar to the general population); however, this necessitated repeated procedures and multiple renal punctures in many cases. Serious complications in the general PCNL population are rare (transfusion 2.5%, urosepsis 2.5%, and pleural or colonic injuries 0.4%), and stone-free rates after a single procedure are 70%. 48 Conclusion Upper tract stone disease is common in patients with SCI and does not seem to have decreased despite advances in other areas of SCI health maintenance. Patients with SCI are at increased risk for stone recurrence, staghorn calculi, and bilateral stone disease. Previous studies have failed to demonstrate a reduction in stone formation in the 1990s. It is unknown if the 21st century has brought about a change in stone incidence. The major risk factors for stones in the SCI population are not easily modifiable or clearly delineated. It seems likely that the lesion level and completeness, bladder management strategy, specific metabolic changes, and propensity for UTIs predispose these patients to upper tract stone disease. There has been a change in the composition of renal stones in this population, likely as a result of advances in the medical and urologic care of patients with SCI. The clinical presentation of stone disease in patients with SCI tends to involve frequent UTIs or urosepsis, and at the time of presentation, patients may need emergency renal drainage. Although stone disease alone does not seem to cause significant end stage renal failure, it may be a contributing factor in patients with multiple risk factors for renal dysfunction. Stone disease carries a mortality rate that may be significant, especially compared with the general population, although only a few small case series have been published. There is little reported on the metabolic management in these patients, or preventative strategies that can be used after the initial stone episode. The proportion of patients who undergo different treatment modalities is largely unknown, with two case series suggesting that the majority of stones are managed by PCNL. The literature suggests that the morbidity associated with PCNL in these patients is considerable. This may be a function of the patient s comorbidities, and the fact that many of these case series included patients from an earlier era of medicine. SWL has stone-free rates of 50% to 70% and is an appropriate minimally invasive option for many patients with SCI. A patient with SCI, however, may need multiple SWL procedures or modalities to be rendered stone free. Ureteroscopy is a common modality used in the general population to manage upper tract stone disease. Traditional limitations of this procedure in patients with SCI have likely been overcome with new flexible scopes; however, the medical literature has not specifically reported on its use among patients with SCI. Disclosure Statement The authors receive speakers fees from Pfizer and Astellas. References 1. Hitzig SL, Tonack M, Campbell KA, et al. Secondary health complications in an aging Canadian spinal cord injury sample. Am J Phys Med Rehabil 2008;87: Chen Y, DeVivo MJ, Roseman JM. Current trend and risk factors for kidney stones in persons with spinal cord injury: A longitudinal study. Spinal Cord 2000;38: DeVivo MJ, Fine PR, Cutter GR, Maetz HM. The risk of renal calculi in spinal cord injury patients. J Urol 1984;131: Donnellan S, Bolton D. The impact of contemporary bladder management techniques on struvite calculi associated with spinal cord injury. 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6 RENAL STONE DISEASE IN SPINAL-CORD INJURED PATIENTS 959 shock wave lithotripsy in spinal cord injury patients. Paraplegia 1995;33: Spirnak JP, Bodner D, Udayashankar S, Resnick MI. Extracorporeal shock wave lithotripsy in traumatic quadriplegic patients: Can it be safely performed without anesthesia? J Urol 1988;139: Pace KT, Tariq N, Dyer SJ, et al. Mechanical percussion, inversion and diuresis for residual lower pole fragments after shock wave lithotripsy: A prospective, single blind, randomized controlled trial. J Urol 2001;166: Ko R, Soucy F, Denstedt JD, Razvi H. Percutaneous nephrolithotomy made easier: A practical guide, tips and tricks. BJU Int 2008;101: Culkin DJ, Wheeler JS, Nemchausky BA, et al. Percutaneous nephrolithotomy: Spinal cord injury vs. ambulatory patients. J Am Paraplegia Soc 1990;13: Armitage J, Irving S, Burgess N. Percutaneous Nephrolithotomy in the United Kingdom: Results of a Prospective Data Registry. Eur Urol Epub ahead of print. Address correspondence to: Blayne Welk, M.D., M.Sc. The University of Western Ontario St Joseph s Health Care 268 Grosvenor Street London, ON N6A 4V2 Canada Blayne.welk@sjhc.london.on.ca Abbreviations Used CT ¼ computed tomography NSCISC ¼ National Spinal Cord Injury Statistical Center PCNL ¼ percutaneous nephrolithotomy SCI ¼ spinal cord injury SWL ¼ shockwave lithotripsy UTI ¼ urinary tract infection VUR ¼ vesicoureteral reflux