Objectives: Successful kidney transplant depends partly on the normal physiologic functioning of the bladder, which involves effective urine storage and emptying. The bladder may become abnormal owing to various urologic and neuropathic disorders. Patients with abnormal bladders need careful management before and after transplant. In this study, we aimed to determine the outcomes of renal transplants in relation to various causes of abnormal bladder.

Materials and Methods: We conducted a retrospective review of 25 patients with abnormal bladder who received 30 renal transplants between 1990 and 2014. The patients were divided into neurologic and urologic groups based on the causes of abnormal bladder. Patient demographics, graft function, survival, and postoperative complications were compared.

Results: The most common urologic cause was posterior urethral valve (14 patients), while the most common neurologic cause was spina bifida (6 patients). There was no statistically significant difference in graft survival at 1, 3, and 5 years between patients with neurologic and urologic causes of abnormal bladder as well as at long-term follow-up. However, the mean estimated glomerular filtration rate at 1, 3, and 5 years was higher among patients with neurologic causes than in those with urologic causes, although the difference was statistically significant only at 1 year (61 ± 34 vs 37 ± 19 mL/min; P = .025). Stone formation was reported only in patients whose abnormal bladder had neurologic causes, and no incidence was reported in patients with urologic causes (20% vs 0%; P = .038). The incidence of other postoperative complications was not statistically significant between the 2 groups.

Conclusions: With careful evaluation and proper preoperative correction of abnormal bladder dys­function and optimization of the emptying and storage functions of the bladder, the causes of abnormal bladder did not appear to impact graft function and survival or overall rate of postoperative complications.

Key words : Posterior urethral valve, Spina bifida, Urethral stricture, Urinary bladder diseases, Urologic diseases, Vesicoureteric reflux

Introduction

End-stage renal disease is associated with structural urologic abnormalities in approximately 15% of patients in the adult population and ≤ 20% to 30% in the pediatric population.¹ However, an abnormal urinary bladder is no longer a contraindication to renal transplant. With appropriate selection, patient and graft survival do not significantly differ from those of the general transplant population.² However, patients with an abnormal bladder need careful evaluation to plan the most satisfactory technical approach to the transplant procedure.³

The normal urinary bladder stores urine at low pressure, does not leak, and completely empties by natural voiding. A urinary bladder may be abnormal due to neuropathy, bladder outlet obstruction (of the posterior urethral valve [PUV] or due to urethral stricture), or acquired bladder disease (eg, caused by interstitial cystitis, postradiotherapy changes, fibrosis from intravesical chemotherapy, or a perivesicular scar from a pelvic hematoma).⁴ The aim of this study was to determine the effects of different causes of bladder abnormality on graft survival outcomes after renal transplant.

Materials and Methods

This was a single-center, retrospective review of the electronic and paper records of patients with pretransplant structural and/or functional bladder abnormalities who received a kidney transplant between 1990 and 2014. Patients were categorized into 2 groups according to the causes of abnormal bladder: neurologic or urologic.

Data were collected between May and September 2015. Endpoints were transplant failure or last follow-up at the end of the study. Graft failure was defined as estimated glomerular filtration rate (eGFR) < 15 mL/min. Information about patient demographics, type of donor kidney, number of transplants, previous urologic operations, and op­tions for abnormal bladder management were collected. Graft function, graft survival, and post­operative complications were compared between the 2 groups. Statistical analyses were done using IBM SPSS Statistics software for Windows (version 20.0, IBM Corp., Armonk, NY, USA). The t test was used to derive the mean, and the chi-square test was used to obtain the categorical variable. P values < .05 were considered significant.

The study protocol was approved by the ethics committee of the Faculty of Medicine, Menofia University.

Results

Patient characteristics
The study included 30 patients who had received ≥ 1 transplant (25 patients received 1 transplant; 5 patients received 2 transplants). For statistical purposes, each transplant was considered to be a separate case. Patients were followed up for ≤ 21 years (mean ± SD, 106 ± 88 mo).

In these patients, abnormal bladder was attributed to urologic causes in 20 patients and neurologic causes in 10 patients. Urologic causes included bladder outlet obstruction at the PUV (14 patients), primary vesicoureteric reflux (4 patients), urethral stricture (1 patient), and epispadius (1 patient). Neurologic causes included neuropathic bladder secondary to spina bifida (6 patients), paraplegia (1 patient), diabetic autonomic neuropathy (1 patient), sacral agenesis and cloacal anomalies (1 patient), and VATER association syndrome (1 patient) (the co-occurrence of the birth defects of vertebral anomalies, anal atresia, tracheoesophageal fistula and/or esophageal atresia, and renal and radial anomalies).

Of the patients with urologic causes of abnormal bladder, 18 (90%) were men compared with 5 patients (50%) with neurologic causes (P = .015). Patients with urologic causes of abnormal bladder received their renal transplant at a younger age (28 ± 16 y) than patients with abnormal bladder due to neurologic causes (39 ± 15 y), although this difference did not reach statistical significance (P = .10). All other patient characteristics did not significantly differ between both groups, as shown in Table 1.

Abnormal bladder management
To make the bladder safe and suitable for kidney transplant, surgical rehabilitation of the bladder (urinary diversion, bladder augmentation, or arti­ficial urethral sphincter insertion) was frequently used in patients with neurologic causes (9/10, 90%) but less so in patients with urologic causes (3/20, 15%) (P = .60 for both).

In patients with urologic causes of abnormal bladder, the surgical procedures performed were as follows: Mitrofanoff channel formation in 1 patient with bladder outlet obstruction at the PUV (the patient could not tolerate clean intermittent catheterization [CIC] through the urethra), an ileal conduit in 1 patient with bladder outlet obstruction at the PUV, and vesicostomy in 1 patient with primary reflux (as a form of urinary diversion with stoma bags [the patient had learning difficulties and controlled seizures]). In patients with neurologic causes of abnormal bladder, surgical procedures included bladder augmentation cystoplasty (6 patients), an ileal conduit (1 patient), and an artificial urinary sphincter insertion (2 patients).

Other options for abnormal-bladder manage­ment, such as CIC, suprapubic catheter, and medical treatment, were also used but were not significantly different between both groups. Some patients required more than one management option, such as CIC in patients with bladder augmentation. The different management options for abnormal bladder are shown in Table 2.

Postoperative complications
As shown in Table 3, stone formation was reported in only 2 patients (20%) with abnormal bladders with neurologic causes, but 0 patients with urologic causes (P = .038). There were no statistically significant differences in the incidence of other postoperative complications.

Graft function
Overall graft survival rates in patients with abnormal bladder were 90%, 90%, and 85% at 1, 3, and 5 years posttransplant, as demonstrated in Figure 1. Graft survival at 1, 3, and 5 years was 90%, 87%, and 80% among those with urologic causes of abnormal bladder versus 90%, 88%, and 87% among those with neurologic causes (Figure 2), with no statistical significance (P = 1.0, .91, and .65 at 1, 3, and 5 y).

Mean eGFR at 1, 3, and 5 years was higher among the 10 patients with abnormal bladder due to neurologic causes (61 ± 34 mL/min at 1 y, P = .025; 48 ± 33 mL/min at 3 y, P = .20; and 43 ± 32 mL/min at 5 y, P = .26) than in the 20 patients with urologic causes (37 ± 19 mL/min at 1 y, P = .025; 32 ± 20 mL/min at 3 y, P = .20; and 29 ± 20 mL/min at 5 y, P = .26). However, these data were statistically significant at 1 year only.

On long-term follow-up, there was also no signi­ficant difference between overall graft survival in patients with abnormal bladder due to urologic causes and those with neurologic causes (log rank test, P = .82) as shown by the Kaplan-Meier curves in Figure 2.

Discussion

Studies of renal transplant patients with abnormal bladder have shown conflicting results. Some showed that these patients are poor candidates for renal transplant.^5,6 In contrast, other studies have shown that renal transplant is a safe and effective treatment for end-stage renal disease in children with lower urinary tract abnormalities.^3,7

In our study, urologic causes of abnormal bladder accounted for 20 of the cases (67%), and neurologic causes accounted for 10 cases (33%). The most common urologic causes were bladder outlet obstruction at the PUV in 14 patients (47% of the total population) and vesicoureteric reflux in 4 patients (13%); the most common neurologic cause was spina bifida in 6 patients (20%). Eighteen patients (90%) with urologic causes of abnormal bladder were male compared with 5 (50%) of those with neurologic causes (P = .015). This disparity can be explained by the fact that bladder outlet obstruction at the PUV was the most common urologic cause, and it occurs only in male patients.

In a study done by Mishra and associates (2007), bladder outlet obstruction at the PUV was the cause of abnormal bladder in 33 of 44 (75%) of the cases.4 Also in a study by Rigamonti and colleagues (2005), urologic causes were found in 52 patients (62%), and bladder outlet obstruction at the PUV was the most common cause (in 18 patients, 21%), whereas neuro­logic causes (without specification) were found in 31 patients (37%).⁸

In our study, patients with abnormal bladder due to urologic causes received their renal transplant at an earlier age than those with neurologic causes. Most of these patients presented with renal im­pairment at a younger age, or even at birth, compared with those with neurologic causes, who generally take longer to present with renal failure.

Many studies of renal transplant in patients with bladder outlet obstruction at the PUV were done in children whose mean age was low. For example, in a study done by DeFoor and associates (2003), mean age at transplant in the PUV group was 10.0 years (range, 3.3-20.6 y). Also in a study by Connolly and colleagues (1995), the mean age of patients at the time of kidney transplant was 16.3 years.^9,10

In contrast, patients with spina bifida tend to receive their renal transplant at older ages than those with bladder outlet obstruction at the PUV, as reported by several studies on patients with spina bifida. For example, in a study by Power and colleagues (2002), mean age at the time of transplant was 20.2 years (range, 10-35 y). Also in a study by Little and coworkers (1994), mean age at the time of transplant was 22.5 years (range, 10-36 y).^11,12

Owing to the structural or functional abnormality of the lower urinary tract, multiple operations are usually required to prevent the deterioration of kidney function and the development of end-stage renal disease, which eventually results in dialysis or renal transplant. “Previous urologic operations” include all urologic operations (eg, valve ablation for PUV, urethrotomy for stricture urethra, epispadias repair, ureteric reimplantations, nephrectomy) performed from the diagnosis of the abnormality until renal transplant, to treat either the cause of the abnormal bladder or its complications.

Surgical rehabilitation of the abnormal bladder (eg, reconstructive bladder operations, urinary diversion, or artificial urinary sphincter insertion) is sometimes required to make it safe for the ongoing functioning of the graft and to ensure continence.¹³ In the past, urinary diversion was the usual approach used to bypass the abnormal bladder. At present, with the use of augmentation cystoplasty and CIC in a small-volume, poor-compliance bladder, a low-pressure and compliant reservoir can be created that is able to protect the upper urinary tract.¹⁴

In our study, 19 patients (95%) with urologic causes required urologic operations, but only 3 of them (15%) required bladder rehabilitation (ie, Mitrofanoff channel creation, an ileal conduit, and a vesicostomy). In contrast, 9 patients (90%) with neurologic causes had required urologic operations, and all of these patients also required bladder rehabilitation operations (eg, augmentation cysto­plasty in 6 patients, ileal conduit in 1 patient, and artificial urinary sphincter insertion in 2 patients).

In a study by Nahas and colleagues (2008), prior to renal transplant, all patients with neurologic causes of bladder dysfunction (8 patients) (mostly due to meningomyelocele and sacral agenesis) and only 9 patients of 34 patients with lower urinary tract abnormality due to urologic causes (5 of 16 patients with PUV, 3 of 15 patients with vesicoureteric reflux, and 1 of 3 patients with prune belly syndrome) underwent surgical procedures on the bladder to create a reservoir with good capacity, adequate compliance, and efficient bladder drainage. These surgical procedures included bladder augmentation in 15 patients (ureterocystoplasty in 6, entero­cystoplasty in 9), continent urinary diversion in 2 patients, autoaugmentation in 1 patient, and the Mitrofanoff procedure at the bladder for easier drainage in 1 patient.¹⁵

In our study, the overall graft survival rates in patients with abnormal bladder were 90%, 90%, and 85% at 1, 3, and 5 years—slightly higher than those reported by Otukesh and associates (2005), who reported graft survival at 1, 3, and 5 years among 48 patients with abnormal bladder as 90%, 76%, and 65% regardless of cause.16 Further, in the present study, graft survival rates in the patient subgroups with urologic causes (90%, 87%, and 80%) and neurologic causes (90%, 88%, and 87%) were higher than those reported by Otukesh et al. (2005), although their sample size was larger (48 vs 30 patients).

Urinary tract infection (UTI) after renal transplant is a common event and affects > 75% of adult and 30% of pediatric transplant recipients. It might present as either asymptomatic bacteriuria or symptomatic infection.¹⁷ The rate of UTIs among patients with abnormal bladder tends to be high.^18,19 This may be in part due to the frequent use of CIC and the different surgical interventions required to repair the bladder, such as bladder augmentation and urinary diversion.

In our study, all 10 patients (100%) with neuro­logic causes of abnormal bladder had UTI episodes that required hospital admission compared with 17 patients (85%) with urologic causes. Furthermore, patients with neurologic causes of abnormal bladder experienced more UTI episodes requiring hos­pitalization (4.5 ± 2.4) than did patients with urologic causes (3.8 ± 3.3). Although this difference was not statistically significant (P = .61), it may be better delineated in a larger study group. This high rate of UTIs might have been caused by the high number of augmentation cystoplasty and CIC procedures in patients with abnormal bladder due to neurologic causes rather than urologic causes. The use of prophylactic antibiotic therapy with effective bladder drainage could reduce the incidence of symptomatic UTI in these patients.

Compared with our study, the study done by Salomon and colleagues (1997) on renal transplant in PUV obstruction patients showed that the incidence of UTI was lower: 14 of 80 patients (17.5%) in their study group compared with 36 of 126 patients (28.5%) in their control group, with no significant differences (P > .05).20 Furthermore, in a study by Power and associates (2002) on patients with spina bifida, only 6 of 16 patients (37.5%) developed 13 episodes of urosepsis that required hospital admission to administer intravenous antibiotics and place an indwelling catheter.¹¹

According to the literature, urinary stones occur in 8% to 52% of patients who undergo bladder augmentation.²¹ In a study done by Capizzi and associates (2004), kidney stones occurred in only 1 patient who had undergone ileocystoplasty and the Mitrofanoff stoma procedure.²² A single incidence of urinary stones was also reported by DeFoor’s group (2003) and Hatch’s group (2001).^18,23

In the present study, among all urologic com­plications, the formation of urinary stones was reported only in 2 patients (20%) with neurologic causes, and an incidence of 0 was reported among patients with urologic causes (0%; P = .038). One patient with neuropathic bladder due to spina bifida who had an ileal conduit placed at the age of 4 years experienced recurrent ureteric stones that were managed endoscopically. The other patient with neuropathic bladder due to VATER syndrome had recurrent bladder stones in the augmented bladder. All other postoperative complications did not significantly differ between the 2 groups.

Limitations of this study include its small sample size (N = 30), retrospective design, and unequal study group arms (20 for neurologic causes and 10 for urologic causes), which might explain the nonstatistically significant differences between the 2 groups in many parameters. Renal transplant outcomes need larger-scale studies to confirm or reject these differences. Despite these limitations, we were able to report on the impact that different causes of abnormal bladder had on renal transplant outcomes. If confirmed by larger or multicenter studies, these results could help with proper patient selection and preparation for renal transplant.

In conclusion, the cause of abnormal bladder did not appear to affect renal graft function, graft survival, or overall postoperative complications. Individualized evaluation of the lower urinary tract according to the cause of abnormal bladder is needed to plan the most satisfactory disease management options, and bladder reconstruction should be frequently considered in patients with neurogenic bladder dysfunction.

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