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Mitrofanoff for Valve Bladder Syndrome: Effect on Urinary Tract and Renal Function
Mitrofanoff for Valve Bladder Syndrome: Effect on Urinary Tract and Renal Function Thomas King,* Robert Coleman and Karan Parashar From the Birmingham Children’s Hospital, National Health Service Foundation Trust, Birmingham, United Kingdom
Purpose: Despite early diagnosis and valve ablation, progressive renal impairment develops in a significant proportion of boys born with posterior urethral valves. Bladder dysfunction is thought to have an important role in the etiology of this renal deterioration. We report the outcome of treating bladder dysfunction with clean intermittent catheterization and overnight drainage via a Mitrofanoff appendicovesicostomy with respect to upper tract imaging, urodynamic findings and renal function. Materials and Methods: All patients were established on a clean intermittent catheterization program via the Mitrofanoff stoma, including 3 or 4 daytime catheterizations and overnight drainage with an indwelling catheter. We analyzed trends in serum creatinine, renal ultrasound appearance and urodynamic data. Results: Mitrofanoff formation was performed in 24 patients with valve bladder syndrome. Median followup was 6.2 years. Hydronephrosis, quantified by combined anteroposterior diameter measurements of the renal pelvis, significantly improved with a mean combined anteroposterior diameter reduction of 14.2 mm (95% CI 7.6e20.9, p 0.001). Overall bladder dysfunction improved. Capacity was decreased in 9 of 12 patients (75%) initially compared with 12 of 21 (57%) after Mitrofanoff surgery (p ¼ 0.457). Compliance was poor in 75% of patients initially vs 28.6% at followup (p ¼ 0.014). Despite improvements in hydronephrosis and urodynamic parameters the mean estimated glomerular filtration rate deteriorated. End stage renal failure developed in 35% of cases during followup. Conclusions: Treatment of valve bladder with clean intermittent catheterization and overnight drainage via a Mitrofanoff stoma can achieve significant improvements in hydronephrosis and bladder dysfunction urodynamic parameters. However, it does not prevent renal deterioration.
Abbreviations and Acronyms APD ¼ renal pelvis anteroposterior diameter CIC ¼ clean intermittent catheterization CKD ¼ chronic kidney disease eGFR ¼ estimated glomerular filtration rate ESRF ¼ end stage renal failure PUV ¼ posterior urethral valves US ¼ ultrasound VUDS ¼ videourodynamics Accepted for publication September 3, 2013. * Correspondence: University Hospital Coventry and Warwickshire, Coventry, West Midlands, United Kingdom.
Key Words: urinary bladder; abnormalities; catheterization; renal insufficiency, chronic; patient compliance
POSTERIOR urethral valves are an uncommon congenital malformation but an important cause of renal impairment in childhood and adolescence with a reported incidence of between 1/3,000 and 1/8,000 live male births.1 Through advances in
prenatal screening, improved valve ablation techniques in the neonatal period and better knowledge of neonatal fluid management the shortterm prognosis is good in males born with PUV. However, late onset renal impairment develops in more than a
0022-5347/14/1915-1517/0 THE JOURNAL OF UROLOGY® © 2014 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2013.09.008 Vol. 191, 1517-1522, May 2014 Printed in U.S.A.
www.jurology.com
j
1517
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MITROFANOFF FOR VALVE BLADDER SYNDROME
third of boys with PUV.2,3 Although the precise relationship is uncertain, it was suggested that bladder dysfunction has a major role in the development of this late renal impairment.2,4 In the early 1980s the term valve bladder syndrome was first used to describe the association of a noncompliant bladder and upper tract dilatation seen in boys with a history of PUV.5 Since then, further urodynamic based studies have identified several bladder dysfunction patterns in boys with PUV and a dilated upper tract after successful valve ablation, including detrusor overactivity, hypocompliance and myogenic failure.6,7 Others suggested that these patterns represent different phases of the same bladder response to prenatal obstruction at different times, for example an overactive hypocompliant bladder progresses toward myogenic failure with time.8 Targeted treatment of bladder dysfunction based on urodynamic findings is expected to improve the renal outcome in boys with PUV. This treatment can take the form of anticholinergic drugs, CIC programs and ultimately bladder augmentation, as needed. In particular, Koff et al reported the importance of achieving nocturnal emptying of the valve bladder.9 We have found that treatment compliance with CIC in this patient group is problematic due to the sensate urethra. Consequently, it has been our practice to perform Mitrofanoff appendicovesicostomy in patients with valve bladder syndrome to facilitate daytime CIC and overnight drainage with the expectation that bladder function and upper tract dilatation would improve and progressive renal impairment would stabilize. We studied the efficacy of our treatment of boys with valve bladder syndrome using daytime CIC and overnight drainage via a Mitrofanoff appendicovesicostomy. We report outcomes, including bladder function, upper tract dilatation and renal outcome.
PATIENTS AND METHODS We performed a retrospective study of patients with posterior urethral valves treated with Mitrofanoff appendicovesicostomy for valve bladder syndrome. Medical records and imaging were reviewed. Intervention timing, serum creatinine trends, renal US appearance and urodynamic data were analyzed. Indications for Mitrofanoff appendicovesicostomy in the study cohort were bladder dysfunction with upper tract deterioration, as evidenced by progressive hydronephrosis, and urodynamic compromise, including poor compliance or poor emptying. All patients were established on a CIC program via the Mitrofanoff stoma, including 3 or 4 daytime catheterizations with overnight drainage via an indwelling catheter.
Hydronephrosis was assessed by US and quantified by measuring the maximum APD. A combined APD value was calculated by adding the measured APDs of the left and right kidneys. A change in the combined APD of more than 5 mm was considered clinically significant to allow for variation in the degree of hydronephrosis secondary to patient hydration and interuser variability among ultrasonographers. We used the Schwartz formula to calculate eGFR. Renal impairment was stratified by CKD stage based on Kidney Disease Outcomes Quality Initiative guidelines.10 A change in eGFR of more than 5 ml/minute/1.73 m2 or a change in CKD stage was considered clinically significant. VUDS were performed using a Model 3011A Uropump III (Life-TechÒ) via an 8Fr suprapubic cystometry catheter (Mediplus, High Wycombe, United Kingdom) placed suprapubically or via the Mitrofanoff stoma. The bladder was filled at 10 ml per second using UrografinÒ 30% for the first 250 ml and continued filling with saline. Expected bladder capacity was calculated using the formula, predicted capacity ¼ (age þ 2) 30 ml. Urodynamic compliance, defined as the change in volume required to increase pressure by 1 cm H2O, was quantified as maximum capacity divided by detrusor pressure at maximum capacity. Compliance less than 15 ml/cm H2O was considered poor. Data are expressed as the mean SE or median with IQR depending on data distribution. Parametric data were analyzed by the t-test. The Fisher exact test was used to analyze urodynamic and US findings in renal outcome groups. One-way MANOVA was done to study potential risk factors for renal impairment progression. We used the Pearson correlation to study the relationship of CKD progression and followup duration. Statistical significance was considered at p <0.05.
RESULTS A Mitrofanoff appendicovesicostomy was created in 24 patients with valve bladder syndrome. In 5 patients a previously created vesicostomy was closed at operation. Mean age at surgery was 8.2 0.7 years. The treatment regimen was well tolerated and poor compliance with CIC was documented in only 3 cases. Three patients required minor revision surgery at a mean of 4.1 1 years. All Mitrofanoff revision surgery was due to stenosis at the mucocutaneous junction. At 8.5 years after Mitrofanoff surgery a patient with ESRF died while awaiting renal transplantation. Mean followup of the renal outcome after the Mitrofanoff procedure was 6.2 0.7 years (median 6.25). Upper Tract US Appearance Renal US was performed before and after Mitrofanoff intervention in 17 patients who had not experienced prior bladder defunctioning via vesicostomy. The mean interval between CIC commencement and US evaluation of the upper tract was 6.3 1.1 months. As quantified by combined
MITROFANOFF FOR VALVE BLADDER SYNDROME
APD measurements, hydronephrosis improved in 12 patients and remained stable in 5. No patient had an increase in hydronephrosis after Mitrofanoff surgery or improvement on 1 side with deterioration on the other side. Mean combined APD at Mitrofanoff surgery was 32.9 4.0 mm. On followup US after the establishment of CIC and overnight drainage mean combined APD was 18.7 1.9 mm, amounting to a 14.2 mm decrease (95% CI 7.6e20.9) in combined APD (p 0.001, fig. 1). This equated to a 43% reduction in APD after the Mitrofanoff procedure. Renal US was performed before and after the intervention in only 2 of the 5 patients in whom vesicostomy was closed at Mitrofanoff surgery. In each case the degree of hydronephrosis remained static after vesicostomy closure with Mitrofanoff procedure. Urodynamics Urodynamic data were available on 22 boys. Five patients had a vesicostomy until closure at Mitrofanoff surgery and did not undergo preoperative urodynamic evaluation. Of the remaining 19 patients preoperative VUDS were available for 12. Postoperative VUDS were available for 21 of the 24 patients treated with the Mitrofanoff procedure. Ten patients had VUDS data available preoperatively and postoperatively. The median interval between VUDS and Mitrofanoff surgery was 12.9 months (IQR 6.9e22.1). The median interval between the Mitrofanoff procedure and followup VUDS was 33.3 months (IQR 23.6e44.4). Bladder capacity was reduced in 9 of 12 patients (75%) with urodynamic data available preoperatively vs 12 of 21 (57%) with data available
Figure 1. Hydronephrosis by mean combined APD before and after Mitrofanoff procedure.
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postoperatively (p ¼ 0.457). Of the 10 patients with paired data available before and after the procedure capacity improved in 4, remained the same in 4 and deteriorated in 2. Poor compliance was noted in 9 of 12 patients (75%) before Mitrofanoff surgery. Compliance improved after CIC initiation with only 6 of 21 patients (28.6%) showing poor compliance on followup urodynamics (p ¼ 0.014). Mean compliance preoperatively and at followup was 17.3 5.6 and 39.4 6.3 ml/cm H2O, respectively, representing a 22.1 ml/cm H2O increase (95% CI 2.8e41.4, p ¼ 0.026, fig. 2). Of the 10 patients with paired data there was clinically significantly improved compliance in 6. Mean compliance improved from 19.1 6.5 to 43.4 8.0 ml/cm H2O, an increase of 24.3 ml/cm H2O (95% CI 6.1e43.4, p ¼ 0.016). The remaining 4 patients had stable compliance, including 2 with poor compliance initially and at followup, and 2 with good compliance. No patient showed a deterioration in compliance. Renal Outcome One patient received a renal transplant before Mitrofanoff surgery and, therefore, he was excluded from renal outcome analysis. The mean interval between Mitrofanoff surgery and the most recent eGFR measurement was 5.2 0.7 years. Of the 23 patients with renal outcome data available 16 showed eGFR deterioration, 6 maintained stable eGFR and 1 had an improvement in eGFR. Mean eGFR deteriorated from 50.5 4.9 to 36 5.3 ml/minute/1.73 m2, equating to a mean eGFR reduction of 15.5 ml/minute/1.73 m2 (95% CI 5.3e23.8, p ¼ 0.004, fig. 3). The table shows progression by CKD stage. Two of the 3 patients with
Figure 2. Mean bladder compliance before and after Mitrofanoff procedure.
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MITROFANOFF FOR VALVE BLADDER SYNDROME
Figure 3. eGFR at Mitrofanoff procedure and late followup
poor treatment compliance progressed from CKD stage 3 to 5 while 1 retained stable renal function at CKD 3. Progressive Renal Deterioration Risk Factors We performed multivariate analysis of risk factors for progressive chronic renal impairment. Patients who underwent transplantation before the Mitrofanoff procedure and those with CKD 5 at operation were excluded from study, leaving 21 available for multivariate analysis. Potential study risk factors were age at initial valve resection, age and combined APD at Mitrofanoff surgery, combined APD at followup US, the change in combined APD and bladder compliance postoperatively, and eGFR at surgery. The MANOVA effect was not statistically significant (F[6,10] ¼ 0.535, p ¼ 0.771, Wilk L ¼ 0.757). No analyzed potential risk factor was associated with progressive chronic renal impairment. There was a significant correlation between followup duration and the change in eGFR with a greater change noted for longer followup (r ¼ e0.51, r2 ¼ 0.255, p ¼ 0.019). This suggests that loss of eGFR in patients with a valve bladder is linear and progressive with time (fig. 4). Progression of CRF by CKD stage Initial CKD Stage (No. pts) CKD 1 (1) CKD 2 (7) CKD 3 (11) CKD 4 (2) CKD 5 (2)
CKD Stage at Followup (No. pts) CKD3 CKD2 CKD3 CKD4 CKD2 CKD3 CKD5 CKD4 CKD5 CKD 5
(1) (3) (3) (1) (1) (5) (5) (1) (1) (2)
Figure 4. Change in eGFR during followup after Mitrofanoff procedure.
DISCUSSION Patients with valve bladder syndrome have a renal concentrating defect with resultant polyuria as well as relative bladder anesthesia, gross hydroureteronephrosis and impaired bladder function. Together this results in residual and pseudo post-void residual urine. The valve bladder is never empty and physiological bladder cycling is impaired. At night polyuria together with poor sensation culminates in enuresis and high pressure urine storage with subsequent renal deterioration. Mitrofanoff appendicovesicostomy in these patients allows the detrusor and, thus, the bladder to fill and empty without painful urethral catheterization. It also facilitates overnight bladder drainage without the risk of urethral erosion. Since this study was retrospective, data availability, particularly urodynamic data before the Mitrofanoff procedure, was a significant limiting factor, as was the overall small size of the series. Despite these limitations we noted clinically and statistically significant improvements in the urinary tract. Mitrofanoff surgery with daytime CIC and overnight drainage resulted in improvement in upper tract dilatation and bladder compliance. Bladder capacity was difficult to evaluate since we routinely stop filling if there is significant reflux, high detrusor pressure (greater than 40 cm H2O), at patient request or when predicted capacity is attained. Therefore, these data may underestimate maximal cystometric capacity. Bladder dysfunction is a common clinical problem in boys with PUV. It develops in up to 75% of such patients despite adequate ablation of the obstructing valves.7
MITROFANOFF FOR VALVE BLADDER SYNDROME
Although bladder dysfunction is widely considered an important etiological factor in the late onset renal impairment associated with PUV, the precise relationship is not clear. Parkhouse et al described a worse renal outcome in boys who were incontinent at 5 years despite normal renal function in infancy.2 Lopez Pereira et al found that 68% of patients with PUV and ESRF had abnormal urodynamics.4 Ansari et al similarly reported that bladder dysfunction was an independent risk factor for ESRF.11 However, in a similar study Sarhan et al did not observe that bladder dysfunction was a significant risk factor for renal impairment on multivariate analysis.12 Earlier studies showed that CIC treatment can result in improved bladder and renal function.13,14 Adding nocturnal bladder emptying was suggested to offer significant further benefits since the persistent nighttime bladder over distension driven by decreased sensation and persistent polyuria15 is overcome and the bladder is allowed to cycle.9 The results of our study confirm that urodynamic parameters and hydronephrosis can be significantly improved through daytime bladder cycling via CIC and overnight bladder drainage. Although dramatic improvements could be achieved, in our series they did not translate into improvements in renal outcome. During followup renal function deteriorated in most of our patients and ESRF developed in a third of them. Continued renal deterioration despite optimized lower tract function may be due to irreversible prenatal damage to the nephron. We believe that although bladder dysfunction may adversely affect renal outcome if left untreated, it is not the primary factor that causes such a significant proportion of boys with valves to have end stage renal disease in late childhood or adolescence. Renal impairment is likely to be multifactorial with bladder dysfunction representing an important, treatable contributory factor. However, this is not the only cause. Others previously noted that normal urodynamic studies do not preclude deterioration in renal function in PUV cases.16 The picture of
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a decrease in renal function despite the correction of urodynamic parameters and hydronephrosis in many patients in our series may be explained by prenatally damaged kidneys decompensating with the additional demands of preadolescent growth. It is unclear whether this damage was sustained during initial obstruction during gestation, or from bladder dysfunction before treatment or other insults, such as urinary tract infection. We stress that bladder dysfunction and upper tract dilatation should never be accepted in a patient with PUV and treatment for these conditions is always warranted. Nevertheless, successful treatment of bladder dysfunction should not be considered a guarantee of a good renal prognosis. Close followup is still required, particularly during the transition from pediatric to adult urological care. While improvement in urodynamic parameters does not result in the prevention of progressive renal impairment, that progression is likely slowed by correcting the valve bladder by preventing further insult to already compromised kidneys. Renal deterioration may not be arrested but there are several other distinct advantages in managing valve bladder with Mitrofanoff. The facility to drain the bladder overnight results in nighttime continence, of which the benefits are often underestimated by patients and parents. Also, the improvement in bladder function and drainage ensures a safe bladder for possible future renal transplantation.
CONCLUSIONS Our study confirms our hypothesis that bladder cycling and overnight drainage result in significant improvement in the urodynamic parameters of bladder dysfunction and hydronephrosis. However, renal function was not stabilized by these improvements, as expected. Patients with valve bladder syndrome tend to progress to ESRF despite adequate, timely lower tract management. In patients with PUV the main determinant of the ultimate development of ESRF may occur prenatally.
REFERENCES 1. Yohannes P and Hanna M: Current trends in management of posterior urethral valves. Urology 2002; 60: 947. 2. Parkhouse H, Barratt T, Dillon M et al: Long term outcome of boys with posterior urethral valves. Br J Urol 1988; 62: 59. 3. Holmdahl G and Sillen U: Boys with posterior urethral valves: outcome concerning renal function, bladder function and paternity at ages 31 to 44 years. J Urol 2005; 174: 1031.
4. Lopez Pereira P, Martinez Urrutia M, Espinosa L et al: Bladder dysfunction as a prognostic factor in patients with posterior urethral valves. BJU Int 2002; 90: 308. 5. Mitchell M: Valve bladder syndrome. Presented at annual meeting of North Central Section, American Urological Association, Hamilton, Bermuda, October 1980. 6. Peters C, Bolkier M, Bauer S et al: The urodynamic consequences of posterior urethral valves. J Urol 1990; 144: 122.
7. Parkhouse H and Woodhouse C: Long term status of patients with posterior urethral valves. Urol Clin North Am 1990; 17: 373. 8. Holmdahl G, Sillen U, Hanson E et al: Bladder dysfunction in boys with posterior urethral valves before and after puberty. J Urol 1996; 155: 694. 9. Koff S, Mutabagani K and Jayanthi V: The valve bladder syndrome; pathophysiology and treatment with nocturnal bladder emptying. J Urol 2002; 167: 291.
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10. Rutkowski M, Mann W, Derose S et al: Implementing KDOQI CKD definition and staging guidelines in Southern California Kaiser Permanente. Am J Kidney Dis, suppl., 2009; 53: S86.
11. Ansari M, Gulia A, Srivastava A et al: Risk factors for progression to end-stage renal disease in children with posterior urethral valves. J Pediatr Urol 2010; 6: 261.
MITROFANOFF FOR VALVE BLADDER SYNDROME
12. Sarhan O, El-Ghoneimi A, Helmy T et al: Posterior urethral valves: multivariate analysis of factors affecting final renal outcome. J Urol 2011; 185: 2491. 13. Campaiola J, Perlmutter A and Steinhardt G: Noncompliant bladder resulting from posterior urethral valves. J Urol 1985; 134: 708. 14. Holmdahl G, Sillen U, Hellstr€om A et al: Does treatment with clean intermittent catheterization in boys with posterior urethral valves
affect bladder and renal function? J Urol 2003; 170: 1681. 15. Dineen M, Duffy P, Barratt T et al: Persistent polyuria after posterior urethral valves. Br J Urol 1995; 75: 236. 16. Ghanem M, Wolffebuttel K, De Vylder A et al: Long-term bladder dysfunction and renal function in boys with posterior urethral valves based on urodynamic findings. J Urol 2004; 171: 2409.
Purpose: Despite early diagnosis and valve ablation, progressive renal impairment develops in a significant proportion of boys born with posterior urethral valves. Bladder dysfunction is thought to have an important role in the etiology of this renal deterioration. We report the outcome of treating bladder dysfunction with clean intermittent catheterization and overnight drainage via a Mitrofanoff appendicovesicostomy with respect to upper tract imaging, urodynamic findings and renal function. Materials and Methods: All patients were established on a clean intermittent catheterization program via the Mitrofanoff stoma, including 3 or 4 daytime catheterizations and overnight drainage with an indwelling catheter. We analyzed trends in serum creatinine, renal ultrasound appearance and urodynamic data. Results: Mitrofanoff formation was performed in 24 patients with valve bladder syndrome. Median followup was 6.2 years. Hydronephrosis, quantified by combined anteroposterior diameter measurements of the renal pelvis, significantly improved with a mean combined anteroposterior diameter reduction of 14.2 mm (95% CI 7.6e20.9, p 0.001). Overall bladder dysfunction improved. Capacity was decreased in 9 of 12 patients (75%) initially compared with 12 of 21 (57%) after Mitrofanoff surgery (p ¼ 0.457). Compliance was poor in 75% of patients initially vs 28.6% at followup (p ¼ 0.014). Despite improvements in hydronephrosis and urodynamic parameters the mean estimated glomerular filtration rate deteriorated. End stage renal failure developed in 35% of cases during followup. Conclusions: Treatment of valve bladder with clean intermittent catheterization and overnight drainage via a Mitrofanoff stoma can achieve significant improvements in hydronephrosis and bladder dysfunction urodynamic parameters. However, it does not prevent renal deterioration.
Abbreviations and Acronyms APD ¼ renal pelvis anteroposterior diameter CIC ¼ clean intermittent catheterization CKD ¼ chronic kidney disease eGFR ¼ estimated glomerular filtration rate ESRF ¼ end stage renal failure PUV ¼ posterior urethral valves US ¼ ultrasound VUDS ¼ videourodynamics Accepted for publication September 3, 2013. * Correspondence: University Hospital Coventry and Warwickshire, Coventry, West Midlands, United Kingdom.
Key Words: urinary bladder; abnormalities; catheterization; renal insufficiency, chronic; patient compliance
POSTERIOR urethral valves are an uncommon congenital malformation but an important cause of renal impairment in childhood and adolescence with a reported incidence of between 1/3,000 and 1/8,000 live male births.1 Through advances in
prenatal screening, improved valve ablation techniques in the neonatal period and better knowledge of neonatal fluid management the shortterm prognosis is good in males born with PUV. However, late onset renal impairment develops in more than a
0022-5347/14/1915-1517/0 THE JOURNAL OF UROLOGY® © 2014 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2013.09.008 Vol. 191, 1517-1522, May 2014 Printed in U.S.A.
www.jurology.com
j
1517
1518
MITROFANOFF FOR VALVE BLADDER SYNDROME
third of boys with PUV.2,3 Although the precise relationship is uncertain, it was suggested that bladder dysfunction has a major role in the development of this late renal impairment.2,4 In the early 1980s the term valve bladder syndrome was first used to describe the association of a noncompliant bladder and upper tract dilatation seen in boys with a history of PUV.5 Since then, further urodynamic based studies have identified several bladder dysfunction patterns in boys with PUV and a dilated upper tract after successful valve ablation, including detrusor overactivity, hypocompliance and myogenic failure.6,7 Others suggested that these patterns represent different phases of the same bladder response to prenatal obstruction at different times, for example an overactive hypocompliant bladder progresses toward myogenic failure with time.8 Targeted treatment of bladder dysfunction based on urodynamic findings is expected to improve the renal outcome in boys with PUV. This treatment can take the form of anticholinergic drugs, CIC programs and ultimately bladder augmentation, as needed. In particular, Koff et al reported the importance of achieving nocturnal emptying of the valve bladder.9 We have found that treatment compliance with CIC in this patient group is problematic due to the sensate urethra. Consequently, it has been our practice to perform Mitrofanoff appendicovesicostomy in patients with valve bladder syndrome to facilitate daytime CIC and overnight drainage with the expectation that bladder function and upper tract dilatation would improve and progressive renal impairment would stabilize. We studied the efficacy of our treatment of boys with valve bladder syndrome using daytime CIC and overnight drainage via a Mitrofanoff appendicovesicostomy. We report outcomes, including bladder function, upper tract dilatation and renal outcome.
PATIENTS AND METHODS We performed a retrospective study of patients with posterior urethral valves treated with Mitrofanoff appendicovesicostomy for valve bladder syndrome. Medical records and imaging were reviewed. Intervention timing, serum creatinine trends, renal US appearance and urodynamic data were analyzed. Indications for Mitrofanoff appendicovesicostomy in the study cohort were bladder dysfunction with upper tract deterioration, as evidenced by progressive hydronephrosis, and urodynamic compromise, including poor compliance or poor emptying. All patients were established on a CIC program via the Mitrofanoff stoma, including 3 or 4 daytime catheterizations with overnight drainage via an indwelling catheter.
Hydronephrosis was assessed by US and quantified by measuring the maximum APD. A combined APD value was calculated by adding the measured APDs of the left and right kidneys. A change in the combined APD of more than 5 mm was considered clinically significant to allow for variation in the degree of hydronephrosis secondary to patient hydration and interuser variability among ultrasonographers. We used the Schwartz formula to calculate eGFR. Renal impairment was stratified by CKD stage based on Kidney Disease Outcomes Quality Initiative guidelines.10 A change in eGFR of more than 5 ml/minute/1.73 m2 or a change in CKD stage was considered clinically significant. VUDS were performed using a Model 3011A Uropump III (Life-TechÒ) via an 8Fr suprapubic cystometry catheter (Mediplus, High Wycombe, United Kingdom) placed suprapubically or via the Mitrofanoff stoma. The bladder was filled at 10 ml per second using UrografinÒ 30% for the first 250 ml and continued filling with saline. Expected bladder capacity was calculated using the formula, predicted capacity ¼ (age þ 2) 30 ml. Urodynamic compliance, defined as the change in volume required to increase pressure by 1 cm H2O, was quantified as maximum capacity divided by detrusor pressure at maximum capacity. Compliance less than 15 ml/cm H2O was considered poor. Data are expressed as the mean SE or median with IQR depending on data distribution. Parametric data were analyzed by the t-test. The Fisher exact test was used to analyze urodynamic and US findings in renal outcome groups. One-way MANOVA was done to study potential risk factors for renal impairment progression. We used the Pearson correlation to study the relationship of CKD progression and followup duration. Statistical significance was considered at p <0.05.
RESULTS A Mitrofanoff appendicovesicostomy was created in 24 patients with valve bladder syndrome. In 5 patients a previously created vesicostomy was closed at operation. Mean age at surgery was 8.2 0.7 years. The treatment regimen was well tolerated and poor compliance with CIC was documented in only 3 cases. Three patients required minor revision surgery at a mean of 4.1 1 years. All Mitrofanoff revision surgery was due to stenosis at the mucocutaneous junction. At 8.5 years after Mitrofanoff surgery a patient with ESRF died while awaiting renal transplantation. Mean followup of the renal outcome after the Mitrofanoff procedure was 6.2 0.7 years (median 6.25). Upper Tract US Appearance Renal US was performed before and after Mitrofanoff intervention in 17 patients who had not experienced prior bladder defunctioning via vesicostomy. The mean interval between CIC commencement and US evaluation of the upper tract was 6.3 1.1 months. As quantified by combined
MITROFANOFF FOR VALVE BLADDER SYNDROME
APD measurements, hydronephrosis improved in 12 patients and remained stable in 5. No patient had an increase in hydronephrosis after Mitrofanoff surgery or improvement on 1 side with deterioration on the other side. Mean combined APD at Mitrofanoff surgery was 32.9 4.0 mm. On followup US after the establishment of CIC and overnight drainage mean combined APD was 18.7 1.9 mm, amounting to a 14.2 mm decrease (95% CI 7.6e20.9) in combined APD (p 0.001, fig. 1). This equated to a 43% reduction in APD after the Mitrofanoff procedure. Renal US was performed before and after the intervention in only 2 of the 5 patients in whom vesicostomy was closed at Mitrofanoff surgery. In each case the degree of hydronephrosis remained static after vesicostomy closure with Mitrofanoff procedure. Urodynamics Urodynamic data were available on 22 boys. Five patients had a vesicostomy until closure at Mitrofanoff surgery and did not undergo preoperative urodynamic evaluation. Of the remaining 19 patients preoperative VUDS were available for 12. Postoperative VUDS were available for 21 of the 24 patients treated with the Mitrofanoff procedure. Ten patients had VUDS data available preoperatively and postoperatively. The median interval between VUDS and Mitrofanoff surgery was 12.9 months (IQR 6.9e22.1). The median interval between the Mitrofanoff procedure and followup VUDS was 33.3 months (IQR 23.6e44.4). Bladder capacity was reduced in 9 of 12 patients (75%) with urodynamic data available preoperatively vs 12 of 21 (57%) with data available
Figure 1. Hydronephrosis by mean combined APD before and after Mitrofanoff procedure.
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postoperatively (p ¼ 0.457). Of the 10 patients with paired data available before and after the procedure capacity improved in 4, remained the same in 4 and deteriorated in 2. Poor compliance was noted in 9 of 12 patients (75%) before Mitrofanoff surgery. Compliance improved after CIC initiation with only 6 of 21 patients (28.6%) showing poor compliance on followup urodynamics (p ¼ 0.014). Mean compliance preoperatively and at followup was 17.3 5.6 and 39.4 6.3 ml/cm H2O, respectively, representing a 22.1 ml/cm H2O increase (95% CI 2.8e41.4, p ¼ 0.026, fig. 2). Of the 10 patients with paired data there was clinically significantly improved compliance in 6. Mean compliance improved from 19.1 6.5 to 43.4 8.0 ml/cm H2O, an increase of 24.3 ml/cm H2O (95% CI 6.1e43.4, p ¼ 0.016). The remaining 4 patients had stable compliance, including 2 with poor compliance initially and at followup, and 2 with good compliance. No patient showed a deterioration in compliance. Renal Outcome One patient received a renal transplant before Mitrofanoff surgery and, therefore, he was excluded from renal outcome analysis. The mean interval between Mitrofanoff surgery and the most recent eGFR measurement was 5.2 0.7 years. Of the 23 patients with renal outcome data available 16 showed eGFR deterioration, 6 maintained stable eGFR and 1 had an improvement in eGFR. Mean eGFR deteriorated from 50.5 4.9 to 36 5.3 ml/minute/1.73 m2, equating to a mean eGFR reduction of 15.5 ml/minute/1.73 m2 (95% CI 5.3e23.8, p ¼ 0.004, fig. 3). The table shows progression by CKD stage. Two of the 3 patients with
Figure 2. Mean bladder compliance before and after Mitrofanoff procedure.
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MITROFANOFF FOR VALVE BLADDER SYNDROME
Figure 3. eGFR at Mitrofanoff procedure and late followup
poor treatment compliance progressed from CKD stage 3 to 5 while 1 retained stable renal function at CKD 3. Progressive Renal Deterioration Risk Factors We performed multivariate analysis of risk factors for progressive chronic renal impairment. Patients who underwent transplantation before the Mitrofanoff procedure and those with CKD 5 at operation were excluded from study, leaving 21 available for multivariate analysis. Potential study risk factors were age at initial valve resection, age and combined APD at Mitrofanoff surgery, combined APD at followup US, the change in combined APD and bladder compliance postoperatively, and eGFR at surgery. The MANOVA effect was not statistically significant (F[6,10] ¼ 0.535, p ¼ 0.771, Wilk L ¼ 0.757). No analyzed potential risk factor was associated with progressive chronic renal impairment. There was a significant correlation between followup duration and the change in eGFR with a greater change noted for longer followup (r ¼ e0.51, r2 ¼ 0.255, p ¼ 0.019). This suggests that loss of eGFR in patients with a valve bladder is linear and progressive with time (fig. 4). Progression of CRF by CKD stage Initial CKD Stage (No. pts) CKD 1 (1) CKD 2 (7) CKD 3 (11) CKD 4 (2) CKD 5 (2)
CKD Stage at Followup (No. pts) CKD3 CKD2 CKD3 CKD4 CKD2 CKD3 CKD5 CKD4 CKD5 CKD 5
(1) (3) (3) (1) (1) (5) (5) (1) (1) (2)
Figure 4. Change in eGFR during followup after Mitrofanoff procedure.
DISCUSSION Patients with valve bladder syndrome have a renal concentrating defect with resultant polyuria as well as relative bladder anesthesia, gross hydroureteronephrosis and impaired bladder function. Together this results in residual and pseudo post-void residual urine. The valve bladder is never empty and physiological bladder cycling is impaired. At night polyuria together with poor sensation culminates in enuresis and high pressure urine storage with subsequent renal deterioration. Mitrofanoff appendicovesicostomy in these patients allows the detrusor and, thus, the bladder to fill and empty without painful urethral catheterization. It also facilitates overnight bladder drainage without the risk of urethral erosion. Since this study was retrospective, data availability, particularly urodynamic data before the Mitrofanoff procedure, was a significant limiting factor, as was the overall small size of the series. Despite these limitations we noted clinically and statistically significant improvements in the urinary tract. Mitrofanoff surgery with daytime CIC and overnight drainage resulted in improvement in upper tract dilatation and bladder compliance. Bladder capacity was difficult to evaluate since we routinely stop filling if there is significant reflux, high detrusor pressure (greater than 40 cm H2O), at patient request or when predicted capacity is attained. Therefore, these data may underestimate maximal cystometric capacity. Bladder dysfunction is a common clinical problem in boys with PUV. It develops in up to 75% of such patients despite adequate ablation of the obstructing valves.7
MITROFANOFF FOR VALVE BLADDER SYNDROME
Although bladder dysfunction is widely considered an important etiological factor in the late onset renal impairment associated with PUV, the precise relationship is not clear. Parkhouse et al described a worse renal outcome in boys who were incontinent at 5 years despite normal renal function in infancy.2 Lopez Pereira et al found that 68% of patients with PUV and ESRF had abnormal urodynamics.4 Ansari et al similarly reported that bladder dysfunction was an independent risk factor for ESRF.11 However, in a similar study Sarhan et al did not observe that bladder dysfunction was a significant risk factor for renal impairment on multivariate analysis.12 Earlier studies showed that CIC treatment can result in improved bladder and renal function.13,14 Adding nocturnal bladder emptying was suggested to offer significant further benefits since the persistent nighttime bladder over distension driven by decreased sensation and persistent polyuria15 is overcome and the bladder is allowed to cycle.9 The results of our study confirm that urodynamic parameters and hydronephrosis can be significantly improved through daytime bladder cycling via CIC and overnight bladder drainage. Although dramatic improvements could be achieved, in our series they did not translate into improvements in renal outcome. During followup renal function deteriorated in most of our patients and ESRF developed in a third of them. Continued renal deterioration despite optimized lower tract function may be due to irreversible prenatal damage to the nephron. We believe that although bladder dysfunction may adversely affect renal outcome if left untreated, it is not the primary factor that causes such a significant proportion of boys with valves to have end stage renal disease in late childhood or adolescence. Renal impairment is likely to be multifactorial with bladder dysfunction representing an important, treatable contributory factor. However, this is not the only cause. Others previously noted that normal urodynamic studies do not preclude deterioration in renal function in PUV cases.16 The picture of
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a decrease in renal function despite the correction of urodynamic parameters and hydronephrosis in many patients in our series may be explained by prenatally damaged kidneys decompensating with the additional demands of preadolescent growth. It is unclear whether this damage was sustained during initial obstruction during gestation, or from bladder dysfunction before treatment or other insults, such as urinary tract infection. We stress that bladder dysfunction and upper tract dilatation should never be accepted in a patient with PUV and treatment for these conditions is always warranted. Nevertheless, successful treatment of bladder dysfunction should not be considered a guarantee of a good renal prognosis. Close followup is still required, particularly during the transition from pediatric to adult urological care. While improvement in urodynamic parameters does not result in the prevention of progressive renal impairment, that progression is likely slowed by correcting the valve bladder by preventing further insult to already compromised kidneys. Renal deterioration may not be arrested but there are several other distinct advantages in managing valve bladder with Mitrofanoff. The facility to drain the bladder overnight results in nighttime continence, of which the benefits are often underestimated by patients and parents. Also, the improvement in bladder function and drainage ensures a safe bladder for possible future renal transplantation.
CONCLUSIONS Our study confirms our hypothesis that bladder cycling and overnight drainage result in significant improvement in the urodynamic parameters of bladder dysfunction and hydronephrosis. However, renal function was not stabilized by these improvements, as expected. Patients with valve bladder syndrome tend to progress to ESRF despite adequate, timely lower tract management. In patients with PUV the main determinant of the ultimate development of ESRF may occur prenatally.
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MITROFANOFF FOR VALVE BLADDER SYNDROME
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