Urinary Tract Stone Development in Patients With Myelodysplasia Subjected to Augmentation Cystoplasty

Management Update

ManageMent Update Urinary Tract Stone Development in Patients With Myelodysplasia Subjected to Augmentation Cystoplasty Courtney L. Shepard, MD,1 Guaqiao Wang, PhD,2 Betsy D. Hopson, MS,3 Erika B. Bunt,4 Dean G. Assimos, MD4 of Urology, University of Michigan, Ann Arbor, MI; 2Division of Biostatistics, Washington University in St. Louis, St. Louis, MO; 3Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL; 4Department of Urology, University of Alabama at Birmingham, Birmingham, AL 1Department Patients with myelodysplasia who have undergone augmentation cystoplasty are at risk for urinary tract stones. We sought to determine the incidence and risk factors for stone development in this population. The charts of 40 patients with myelodysplasia who have undergone augmentation cystoplasty were reviewed. None had a prior history of urinary tract stones. All patients were seen on an annual basis with plain abdominal imaging, renal ultrasonography, and laboratory testing. Statistical analysis included a multivariable bootstrap resampling method and Student’s t-test. Fifteen (37.5%) patients developed stones, 14 with bladder stones and 1 with a solitary renal stone, at a mean of 26.9 months after augmentation. Five (33.3%) developed recurrent bladder stones. The patient with a renal stone never developed a bladder stone. The mean follow-up for the stone formers was 117.2 months and for non–stone formers was 89.9 months. The stone incidence per year was 6.8%. Risk factors included a decline in serum chloride after augmentation (P 5 .02), female sex, younger age at time of augmentation, longer time period since augmentation, and bowel continence. A significant proportion of patients with myelodysplasia subjected to augmentation cystoplasty develop urinary tract stones, predominantly in the bladder. Dehydration may play a role in development of lower urinary tract stones as the decline in serum chloride suggests contraction alkalosis, which could lead to constipation and improved bowel continence. Therefore, improved hydration should be a goal in this cohort. [Rev Urol. 2017;19(1):11-15 doi: 10.3909/riu0741] ® © 2017 MedReviews , LLC Key words Spina bifida • Neurogenic bladder augmentation • Cystoplasty • Nephrolithiasis Vol. 19 No. 1 • 2017 • Reviews in Urology • 11 Urinary Tract Stone Development in Patients With Myelodysplasia continued A ugmentation cystoplasty is the gold standard treatment of patients with myelodysplasia with poorly compliant and overactive bladders not responsive to conservative measures. In addition to helping preserve the upper urinary tract, this procedure also allows many patients to achieve continence as well as independence, especially when combined with a bladder channel. However, despite being the best available option for many, it is not without significant morbidity.1 Urinary tract stones frequently develop in patients with myelodysplasia who have undergone augmentation cystoplasty, with a reported incidence rate of 6% to 53% and a subsequent recurrence rate of 19% to 44%.2-11 Because of the high incidence of stones, it is recommended that patients undergo annual radiographic evaluation for stones after enterocystoplasty.7 Reported risk factors for stone development that are pertinent to this patient population include recurrent urinary tract infections, lower urinary tract reconstruction utilizing bowel, procedures that increase bladder outlet resistance, abdominal wall stoma, urinary stasis, mucus production, immobility, sensory impairment, vesicoureteral reflux, renal scarring, a thoracic-level spinal defect, other anatomic abnormalities (such as cloacal malformations), metabolic abnormalities (including acidosis), lower urine output, family history, poor nutrition, and indwelling catheter.2,3,13-16 The reported benefit of an irrigation protocol to prevent lower urinary tract stones varies.6,8 Due to the high prevalence of stones in patients with myelodysplasia who have undergone augmentation cystoplasty, it is helpful to know preoperatively which patients are at highest risk of developing stones. This knowledge can change the preoperative assessment and counseling, and help direct postoperative imaging studies. Additionally, by reducing the frequency of imaging in patients at low risk of stones, this can potentially save healthcare dollars. However, to date, there are no known preexisting factors that have been identified that increase the risk of developing urinary tract stones after this procedure.4 The goal of this study is to determine the incidence of stone had a history of urinary tract stones prior to augmentation cystoplasty. All patients and families were instructed to perform clean intermittent catheterization (CIC) at least four times daily and to irrigate their augmented bladders on a daily basis. Imaging reports, clinic notes, and operative reports were reviewed for all 40 patients to identify those patients who developed urinary tract stones. The number of stones, stone events, and stone interventions were recorded. For all patients, we also reviewed … to date, there are no known preexisting factors that have been identified that increase the risk of developing urinary tract stones after this procedure. development in our patients with myelodysplasia who have undergone augmentation cystoplasty, as well as to identify any risk factors for this occurrence. Materials and Methods Most of the patients with myelodysplasia at Children’s of Alabama (Birmingham, AL) are enrolled in the Center for Disease Control National Spina Bifida Patient Registry. This provides a prospective and retrospective database of 435 patients, of whom 54 (12.4%) have undergone ileal augmentation cystoplasty for management of a neurogenic bladder. We excluded any patient who had undergone augmentation cystoplasty at other institutions because the operative notes, dates of surgery, and preoperative laboratory values were not available. We also excluded patients who had undergone renal transplantation due to concern that their renal function and medications could be a significant confounding factor. Of the initial 54 patients, 40 patients met all inclusion criteria. No patient 12 • Vol. 19 No. 1 • 2017 • Reviews in Urology patient demographics, medical history, surgical history, reported compliance with catheterization and irrigation, and all available laboratory values before and after surgery. Potential risk factors for stone development were then evaluated. This included the following laboratory values before and after bladder augmentation: hematocrit, blood urea nitrogen, serum creatinine, serum chloride, serum bicarbonate, serum calcium, and serum glucose. The laboratory values drawn during preoperative assessment and the most recent results were used for the pre- and postoperative laboratory values. Simultaneous procedures that could potentially increase the risk of stones, including creation of bladder channel, ureteral reimplantation, and bladder neck sling, were included in the analysis. Patient demographics, including sex, level of lesion, ambulatory status, body mass index, age at augmentation, and time in follow-up were reviewed. Factors that could indicate compliance or extent of disease, including bladder and bowel continence, Urinary Tract Stone Development in Patients With Myelodysplasia reported compliance with CIC, history of bladder rupture, presence of hydronephrosis, and history of ulcers or skin breakdown were also evaluated. Statistical analysis included multivariate and univariate analysis using bootstrap resampling, nonparametric analysis, Pearson’s χ2 test, and Student’s t-test. Results The patients who met inclusion criteria included 23 girls and women, and 17 boys and men, comprising 1 Asian patient, 5 black patients, and 34 white patients, with an average age of 15 years (range, 6-24 y). The level of lesion was sacral in 9 patients, thoracic in 10, and lumbar in 21. Of the 40 patients, 15 (37.5%) developed stones at a mean of 26.9 months after augmentation (range, 5-85 stone incidence per year was 6.8%; 19 procedures were performed for the management of these stones: 10 open and 9 endoscopic. Observation was chosen for the patient with the renal stone. Laboratory values were available for 21 of the 25 patients (84%) without stones and for 13 of the 15 patients (87%) with stones. Multivariate analysis demonstrated that the strongest risk factor for development of urinary tract stones after augmentation was the difference in serum chloride before and after augmentation (20.25 in the stone-former group, 2.68 in the stone-free group) with a percentage of the best model of 39.8%. This was also significant in nonparametric analysis (P 5 .02). Multivariate analysis showed that the combination of female sex and a decrease in serum chloride after augmentation were the best two longer follow-up after augmentation (percentage of the best model, 12.9%; Table 1). However, longer follow-up and female sex did not meet significance on univariant analysis (Table 2). Discussion A total of 38% of our patients developed urinary tract stones after augmentation cystoplasty and 12.5% developed recurrent stones. Our initial stone formation rate is consistent with what is reported in the literature (6%-52%). This also holds true for stone recurrence (19%-44%).2-9 Most stone formers developed bladder stones, whereas only one patient developed a solitary renal stone. Other studies, such as the series by Schlomer and colleagues9 and Khoury and colleagues,12 also found that the majority of stones formed after augmentation cystoplasty are bladder stones. We found that the most significant risk factor for developing stones after surgery was a decrease in serum chloride in follow-up after augmentation. We also showed that bowel continence is highly Multivariate analysis showed that the combination of female sex and a decrease in serum chloride after augmentation were the best two predictors of stone development… mo). Fourteen patients developed bladder stones and 1 developed a solitary renal stone. Ten patients (66.6%) had a solitary stone event, whereas 5 (33.3%) developed recurrent stones; the recurrent stones were all bladder stones. The patient with the renal stone never developed a bladder stone. The predictors of stone development (percentage of the best model, 26.8%); the best three predictors … the most significant risk factor for developing stones after surgery was a decrease in serum chloride in follow-up after augmentation. associated with the development of stones. Our theory is that those who were female sex, decrease in serum chloride after augmentation, and TABLe 1 Trends in Stone Formers and Stone-free Patients Status of Stones Difference in Chloride After Augmentation Age at Augmentation (mo) Follow-up After Augmentation (mo) Female Sex (%) Continent of Stool (%) Stone formers Stone free 20.25 2.68 88.4 110.4 107.6 85.6 73 44 53 36 Vol. 19 No. 1 • 2017 • Reviews in Urology • 13 Urinary Tract Stone Development in Patients With Myelodysplasia continued TABLe 2 Potential Risk Factors for Stone Development Risk Factor for Stone Development P Value Decrease in serum chloride after augmentation Longer follow-up after augmentation Age at augmentation Hydronephrosis Female sex History of bladder rupture Compliance with clean intermittent catheterization/irrigation Bowel continence Body mass index Ureteral reimplantation History of skin breakdown Bladder channel Bladder continence Bladder neck sling Ambulatory .02 .09 .11 .11 .12 .16 develop stones likely have contraction alkalosis from dehydration, which not only leads to development of stones, but also leads to some constipation and, therefore, bowel continence. Reduction in serum chloride occurs with contraction alkalosis. The strength of this theory would have been enhanced if there had been a statistically significant difference in serum .17 .19 .30 .35 .39 .412 .412 .59 .74 bicarbonate between those who formed stones and those who did not. Nevertheless, the importance of hydration should be emphasized in this cohort. Although this has not been specifically noted in other studies to our knowledge, Robertson and Woodhouse17 found that patients who developed stones after enterocystoplasty had elevated urinary pH (mean, 6.93) and low urine volume, which is consistent with the same metabolic state. However, in the study by Hamid and associates,16 the urine of the patients who developed stones after enterocystoplasty demonstrated a significantly lower urinary pH level than those who did not form stones (6.49 vs 6.93). Their study did demonstrate that patients who develop stones had significantly lower urine volume and lower fluid intake than those who did not form stones, which are both consistent with dehydration.16 A limitation of our study is that we did not assess urine volume. We did not find that the concurrent surgeries were significantly related to stone development. Although other studies have shown that the creation of a bladder channel is associated with an increased risk of stones, in our study the patients who developed stones were actually less likely to have a bladder channel (47% of patients with stones had bladder channels vs 60% of those without stones), although the difference was not significant (P 5 .41).3,12 Although others have reported that concomitant bladder neck closure/reconstruction was associated with stone risk, this was not true in our series.3 Interestingly, patient- and familyreported noncompliance with CIC and irrigations was not associated with an increased risk of stones. MAin PoinTs • Augmentation cystoplasty is the gold standard treatment of patients with myelodysplasia with poorly compliant and overactive bladders not responsive to conservative measures. However, urinary tract stones frequently develop in patients with myelodysplasia who have undergone augmentation cystoplasty. • The most significant risk factor for developing stones after surgery was a decrease in serum chloride in follow-up after augmentation. Longer follow-up after surgery, female sex, and bowel incontinence are also associated with an increased risk of stones. • Patient- and family-reported noncompliance with clean intermittent catheterization and irrigations was not associated with an increased risk of stones. 14 • Vol. 19 No. 1 • 2017 • Reviews in Urology Urinary Tract Stone Development in Patients With Myelodysplasia This latter finding may be reflective of the utilization of patientand family-reported compliance. Of note, none of the stone formers had a history of bladder rupture. not demonstrate that compliance with CIC and irrigation reduced stone risk, we recommend that it be done. Conclusions Patients with spina bifida subjected to augmentation cystoplasty are at high risk for developing bladder stones, as well as recurrent calculi. We strongly advocate proper hydration to limit these events. Although our results did 9. 10. … patient- and family-reported noncompliance with CIC and irrigations was not associated with an increased risk of stones. There are, undoubtedly, other patient factors not identified in this study that could contribute to the development of lower urinary tract stones in these patients. Candidates include bone health, mobility, and urinary stone risk parameters. 8. 11. References 1. 2. 3. 4. 5. 6. 7. 12. Adams RC, Vachha B, Samuelson ML, et al. Incidence of new onset metabolic acidosis following enterocystoplasty for myelomeningocele. J Urol. 2010;183:302-305. Kaefer M, Hendren WH, Bauer SB, et al. Reservoir calculi: a comparison of reservoirs constructed from stomach and other enteric segments. J Urol. 1998;160:2187-2190. 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Schlomer B, Saperston K, Copp H. 487 cumulative incidence of complications and urologic procedures after augmentation cystoplasty in children. J Urol. 2013;189(suppl):e200. Metcalf PD, Cain MP, Kaefer M, et al. What is the need for additional bladder surgery after bladder augmentation in childhood? J Urol. 2006;176 (4 Pt 2):1801-1805. Berkowitz J, North AC, Tripp R, et al. Mitrofanoff continent catheterizable conduits: top down or bottom up? J Pediatr Urol. 2009;5:122-125. Khoury AE, Salmon M, Doche R, et al. Stone formation after augmentation cystoplasty: the role of intestinal mucus. J Urol. 1997;158:1133-1137. Rizvi SA, Naqvi SA, Hussain Z, et al. Pediatric urolithiasis: developing nation perspectives. J Urol. 2002;168(4 Pt 1):1522-1525. Veenboer PW, Rudd Bosch JL, van Asbeck FW, de Kort LM. Urolithiasis in adult spina bifida patients: study in 260 patients and discussion of the literature. Int Urol Nephrol. 2013;45:695-702. Raj GV, Bennet RT, Preminger GM, et al. The incidence of nephrolithiasis in patients with spinal neural tube defects. J Urol. 1999;162:1238-1242. Hamid R, Robertson WG, Woodhouse CR. Comparison of biochemistry and diet in patients with enterocystoplasty who do and do not form stones. BJU Int. 2008;101:1427-1432. Robertson WG, Woodhouse CR. Metabolic factors in the causation of urinary tract stones in patients with enterocystoplasties. Urol Res. 2006;34:231-238. Vol. 19 No. 1 • 2017 • Reviews in Urology • 15