Bladder Function Evaluation Before Renal Transplantation in Nonurologic Disease: Is It Necessary?

• Daniel Moser Silva^{a, ,} ,
• Alessandro Correia Prudente^a,
• Marilda Mazzali^b,
• Claudio Ferreira Borges^a,
• Carlos D'Ancona^a

 

doi:10.1016/j.urology.2013.09.015

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Progression of renal disease to end-stage renal disease (ESRD) is associated with a reduction of the glomerular filtration rate and urine output. It occurs regardless of the etiology of the primary renal failure.¹ In patients receiving renal replacement therapy, the maintenance of residual diuresis is rare, and the reduction in urinary flow can produce bladder alterations, known as a defunctionalized or dysfunctional bladder (DB).

The need for analysis of bladder function in patients on the waiting list for transplantation remains controversial. Investigators' opinions diverge on whether DB should be investigated or treated before transplantation. No conclusive data are available; thus, perhaps the lack of a definition for DB has contributed to the controversy. The classification of bladder dysfunction secondary to a nonurologic or urologic etiology is the first point to be considered. Bladder dysfunction can occur as a consequence of reduced renal function resulting from nonurologic etiologies, such as diabetes, hypertension, and glomerulonephritis, or can result from alterations in the urinary tract, such as posterior urethral valves, neurogenic bladder, bladder tuberculosis, benign prostatic hyperplasia, prostate cancer, retroperitoneal fibrosis, and urinary lithiasis. Several investigators have supported the investigation and treatment of bladder function before renal transplantation, with most of the studies including urologic etiologies.^{2, 3, 4, 5,6 and 7} However, although a nonurologic etiology has been the main cause of ESRD, studies analyzing the indications for bladder function investigation, the best point for evaluation, and guidelines for treatment are lacking.^{8 and 9}

The urodynamics study has been considered the reference standard for bladder function evaluation. It includes uroflowmetry, cystometry, pressure flow study (PFS), and voiding cystourethrography. DB usually presents with changes in the cystometry and PFS parameters, such as a reduced maximal cystometric capacity, detrusor overactivity, and reduced bladder compliance.^{9, 10 and 11} Anecdotal reports and retrospective series have shown recovery of bladder function after an increase in the post-transplant urine output.¹²Serrano et al¹³ observed bladder function recovery during long-term follow-up in a series of patients with ESRD from urologic causes, including previous surgical urinary diversion. In 2003, Zermann et al¹⁴ suggested the importance of urodynamics study before kidney transplantation in patients with nonurologic ESRD with lower urinary tract symptoms and dysfunctional voiding. Nonetheless, no post-transplant urodynamics evaluation was performed, and some patients could not be classified as having DB because of a high urinary output.¹⁴

Therefore, we evaluated the follow-up cystometry and PFS parameters of patients with nonurologic ESRD who had undergone kidney transplantation.

Material and Methods

The Scientific Review Committee at Campinas University reviewed and approved the protocol for the present study. All participants provided written informed consent before beginning the study.

In the present case-control study, we evaluated 30 of 148 consecutive patients who had undergone kidney-deceased donor transplantation at our institution from April 2009 to June 2010. Because of difficulties related to the unpredictable interval to deceased donor transplantation and logistical issues, we could only access 63 of 148 patients before renal transplantation. Of these 63 patients, 33 were excluded, because they had not satisfied the inclusion and/or exclusion criteria.

The inclusion criteria were age >18 years, ESRD from nonurologic causes, renal replacement therapy for >12 months, and 24-hour urine output <800 mL, measured using a bladder diary. The exclusion criteria were previous urologic surgery and abnormal urinary tract ultrasound or cystourethrography findings (these examinations were mandatory for all candidates for renal transplantation at our institution).

The 30 patients had undergone cystometry and PFS immediately before and 6 months after successful renal transplantation. The group included 11 female and 19 male patients, aged 18-66 years (average 46.5). They had required dialysis for 130-168 months (average 57). The primary cause of ESRD was hypertension in 8, chronic glomerulonephritis in 8, diabetes mellitus in 6, adult polycystic kidney disease in 4, and other nonurologic etiologies in 6 (Table 1).

The data were processed using a 6-six channel urodynamic device (Uro-Master II, version 4.2, SP/BR, DynaMed, Ipswich, MA). Cystometry and PFS were done according to the good practices recommended by the International Continence Society.¹⁵Cystometry was performed with all subjects in the standing position. PFS was performed with the men standing and the women seated. Bladder filling was achieved at a rate of 20 mL/min with saline solution through an 8F urethral catheter. Intravesical pressure was assessed using a 6F urethral catheter, and the abdominal pressure was measured using a 6F catheter with a balloon attached to the tip.

The terminology used to describe the studied parameters followed the American Urological Association Guidelines for Adult Urodynamics and International Continence Society recommendations.^{16 and 17}

The parameters assessed during cystometry were first sensation, first desire to void, maximal cystometric capacity (MCC), bladder compliance, and the presence of detrusor overactivity (DO). The parameters assessed during the PFS were maximal flow rate (Qmax), average flow rate, detrusor pressure at Qmax, and postvoid residual urine volume. In the men, the Abrams-Griffiths (AG) number was calculated. By definition, this number cannot be used with women.¹⁸

Statistical Analysis

A descriptive analysis was obtained with a frequency table of categorical variables and position and dispersion measures of numeric variables. The Wilcoxon test was used in related samples to compare variables between the 2 points (before and 6 months after renal transplantation). Spearman's correlation coefficient was applied to check the linear association among the parameters. This coefficient presents a variation ranging from −1 to 1. Values closer to the extremes indicate a positive or negative correlation, and values closer to 0 do not indicate a correlation. Statistical significance was considered at P <.05, and the statistical analysis was done using the SAS System for Windows, version 9.2 (SAS Institute, Cary, NC).

Results

All the cystometry and PFS parameters were compared individually before and 6 months after renal transplantation. Significant improvement was seen in all the parameters, except for the detrusor pressure at Qmax and the postvoid residual urine volume, which were normal before transplantation (Table 2). The average preoperative AG number was 31.8 (the uncertain zone for obstruction). Once urinary production had begun again after transplantation, the average AG was 15.2, reaching the nonobstructed zone.

Preoperatively, 15 of 30 patients presented with DO. After transplantation, 9 of these 15 subjects (60%) had no DO and 2 (13%) had a decreased amplitude and frequency of DO. Of the remaining 4 patients, 1 (7%) had a worsened involuntary bladder contraction frequency and amplitude and 3 (20%) had no changes in their DO pattern. Finally, 3 patients, who had had no evidence of DO before transplantation, had developed involuntary bladder contractions after transplantation.

The MCC was directly proportional to the 24-hour urine output (Uri24h). However, a correlation between MCC and the duration of dialysis therapy was not observed (Fig. 1). Using this information, we divided the patients into 2 groups: group 1 with Uri24h of <200 mL (n = 14) and group 2 with Uri24h of ≥200 mL (n = 16). The preoperative parameters, including first sensation, first desire to void, compliance, and MCC, were significantly worse in group 1, indicating more intense bladder dysfunction (P <.0001; P = .01; P = .0002; and P = .03, respectively). Despite the preoperative discrepancy, both groups presented with postoperative improvement of the analyzed parameters, reaching the normal standard values ( Table 3).

Comment

Our pretransplantation results have corroborated previous reports, which demonstrated that patients with prolonged oliguria can develop miscellaneous forms of DB, with the most common alterations associated with deterioration of the storage function of the bladder, including the first sensation, first desire to void, MCC, and DO.^{9, 10 and 11}

Mizerski et al¹¹ evaluated a group of 102 patients, without designating the ESRD etiology. Uroflowmetry was performed 2, 4, 8, 12, 16, and 24 weeks after renal transplantation, and a stepwise recovery of the bladder capacity was observed in the defunctionalized bladder. The period required for improvement in the bladder capacity was directly proportional to the pretransplant oliguria period. For patients who were oliguric for ≤12 months, this improvement was observed within 12 weeks after renal transplantation. However, for patients with oliguria for ≤24 months, recovery took longer, usually >24 weeks after surgery.¹¹ These data were considered when we decided to perform the post-transplant investigation at 6 months. Our data have confirmed the conclusions from Mizerski et al¹¹ and also incorporated new concepts of bladder function improvement after kidney transplantation.

The results of the present study have indicated that the degree of bladder deterioration is directly proportional to the residual diuresis volume, as previously suggested.⁹ However, this correlation was not necessarily related to the duration of the dialysis therapy, such as some other series have reported.¹⁰

Patients with ESRD and anuria have usually been included on the renal transplantation waiting list with those with DB; however, evidence of the minimum Uri24h that will lead the bladder to defunctionalization has been poor.¹⁹ Our study has shown that the cystometry and PFS parameters in the group of patients with Uri24h of ≥200 mL were similar to those of patients with a normal bladder. However, the group of patients with Uri24h <200 mL presented with worse cystometry and PFS parameters. This observation suggests that subsequent studies should use the Uri24h value of <200 mL to classify the bladder as defunctionalized.

Another point of interest regarding the DB is the difficulty in performing satisfactory ureteral implantation during renal transplantation. In 1999, Salvatierra et al^{20 and 21}demonstrated good results with intravesical ureteral implantation in a very low capacity bladder (average 18.5 ± 13.1 mL; range 6-45). Other investigators have suggested pyeloureteral or ureteral-ureteral anastomosis using the recipient's native pelvis or ureter.²² In our study, no complications or difficulties were reported with ureteral implantation. We used an extravesical approach, according to the principles of Lich and Gregoir.²³

The frequency and amplitude of DO affecting patients with ESRD before renal transplantation has varied owing to the heterogeneity of the studied groups (range 10%-100%).^{10 and 15} In our study, DO was identified in 50% of the patients. This DO frequency after transplantation was in accordance with previous studies reporting DO symptoms (frequency and nocturia in 54% and 60%).²⁴ Whenever the diagnosis of postrenal transplantation DO is suspected, treatment should be implemented.

Several investigators have contraindicated surgical treatment of prostatic lower urinary tract obstruction before renal transplantation because of the high risk of bladder neck contracture as a consequence of oligoanuria.²⁵ The most accepted strategy has been to postpone the surgical intervention immediately after renal transplantation.^{26 and 27} Our study findings have endorsed this strategy, because significant improvement occurred in the urinary flow (Qmax and average flow rate) and AG number after transplantation. Therefore, we suggest that lower urinary tract symptoms related to benign prostatic obstruction should be treated after diuresis recovery. Only 1 patient presented with an AG number after transplantation that was >40, suggesting benign prostatic obstruction (AG number 65). He also had moderate prostatic symptoms that were controlled with oral α-blockers.

Conclusion

Patients with ESRD and DB secondary to nonurologic causes experienced significant improvement in the cystometry and PFS parameters once renal function and urine output had returned after renal transplantation. Our data suggest that cystometry and PFS are unnecessary before renal transplantation in patient with ESRD of nonurologic causes. We believe that the investigation and treatment of bladder dysfunction, before renal transplantation, should be done only in patients with ESRD of urologic causes and/or previous lower urinary tract surgery.

References