Transplantation and the Abnormal Bladder

12

Transplantation and the Abnormal Bladder ARMAN A. KAHOKEHR and ANDREW C. PETERSON

CHAPTER OUTLINE

Assessment of Lower Urinary Tract Function and Pretransplant Workup Physical Examination and Noninvasive Tests Indications for Invasive Investigations Pretransplant Imaging Normal Cystometric Values Special Pretransplant Issues Methods to Enhance Bladder Emptying Vesicoureteral Reflux and Abnormal Bladder Compliance Timing of Bladder Reconstruction and “Dry-Diversion” Posttransplant Issues Maintenance of Lower Urinary Function

The ability of the urinary bladder to store urine at low pressure and to empty completely at intervals with simultaneous relaxation of the sphincter complex is essential to preserve the integrity of the kidneys and to achieve continence. Although an abnormal lower urinary tract is not a contraindication to renal transplantation, lower urinary tract dysfunction (LUTD) needs to be addressed before and after transplantation. In this chapter we shall discuss the causes, evaluation, and methods of treatment of bladder dysfunction. Abnormal bladder function can be present in both adults and children with end-stage renal disease (ESRD) who are transplant candidates, but the problem is more prevalent in the pediatric age group. About 20% to 30% of children who develop renal failure have potential bladder dysfunction as the etiology of the renal failure or a contributor to ESRD.1,2 Patients at risk for bladder dysfunction include those with a history of posterior urethral valve (PUV), prune-belly syndrome (PBS), neurogenic bladder (NGB), bladder exstrophy, Ochoa and Hinman syndromes, patients with anorectal malformations, and persistence of the cloaca. In some of these conditions, the development of ESRD is frequently a consequence of the congenital anomaly associated with renal dysplasia (PUV, PBS, persistence of the cloaca);3–5 however, in others, such as NGB, whether congenital or acquired, renal damage results from bladder dysfunction and is preventable with good management. When renal failure results from underlying urologic anomalies (e.g., PUV, PBS, NGB), it can be assumed that

Urinary Tract Infections Methods to Achieve Continence Results of Renal Transplantation into Reconstructed and Abnormal Bladders Special Considerations for the Transplant Surgeon Posterior Urethral Valves Prune-Belly Syndrome Male Voiding Dysfunction, BPH/LUTS Female Voiding Dysfunction Conclusion

the abnormal bladder that contributed to the damage of the native kidneys might adversely influence the outcome of the transplant. Many reports have shown that bladder dysfunction can negatively affect graft function if left untreated. Reinberg and colleagues6 first pointed this out in 1988 for children with PUV, and since then other authors have verified these observations.7,8 Correction of structural anomalies and optimization of storage and emptying functions of the bladder are often recommended before transplantation.9 In fact, improvement of bladder function can slow down the progression of renal insufficiency and allow transplantation to be postponed.10 Although in general all anticipated reconstructive procedures on the lower urinary tract are best performed before transplantation, this is not always possible for several reasons. For example, in children before toilet training it may be difficult to predict future continence. When polyuria is present, it may be difficult to predict how the bladder will behave once normal diuresis is restored. Likewise it is difficult to predict future bladder function after a prolonged period of oligo- or anuria. It should also be kept in mind that bladders that seem to have normal function initially may become abnormal over time, such as is seen in cases of valve bladders or in children with tethered spinal cord, and sometimes in adults with bladder outlet obstruction from the prostate. The opposite is also true. For example, a bladder that has inadequate capacity or compliance in the face of polyuria may function adequately after transplantation when normal urine output is restored.11 173

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Assessment of Lower Urinary Tract Function and Pretransplant Workup The general principles of making the bladder useful to receive a renal graft include: (1) providing a method for emptying when spontaneous voiding is not possible, (2) restoring a safe bladder capacity and compliance to protect the graft, and (3) achieving continence. Although urinary incontinence may not affect the functional result of transplantation, restoring continence greatly enhances quality of life.12 ESRD often causes reduced urine production and loss of normal physiologic distention of the bladder, which may lead to a temporary reduction in bladder capacity and loss of compliance. In neurologically and structurally normal patients, this reduction in capacity has been shown to be directly related to the duration of time on dialysis with capacity of less than 150 mL seen after an average of 76 months on dialysis.13 However, it has been shown that bladder capacity improved once cycling of the bladder has been established after transplantation even in those with bladder capacity of less than 100 mL at the time of transplantation.14 A functional bladder may need to be reevaluated over time if the waiting time for renal transplantation is prolonged or if new lower urinary tract symptoms occur. It also is known that LUTD in children and adolescents occurs after transplantation, even when the bladder was normal before renal transplantation, warranting careful posttransplant attention.15,16 The pretransplant urologic evaluation aims to diagnose, treat, and optimize any preexisting LUTD.2,17,18 All patients in ESRD with known or suspected lower genitourinary abnormalities require evaluation of bladder function, and adults with lower urinary tract symptoms (LUTS) should be evaluated by a urologist before transplant. Additionally, we feel that all pediatric patients require complete evaluation of the lower urinary tract before renal transplantation and recommend referral to a pediatric urologist with specialization in LUTD. We perform preoperative evaluation with a detailed history and physical examination that includes a bladder diary kept over several days to record voided volumes and frequency, incontinent episodes, and presence of nocturia or nocturnal enuresis. In anuric patients, the history before the onset of anuria is very valuable.

PHYSICAL EXAMINATION AND NONINVASIVE TESTS On examination we look for scars, stomas, and skeletal deformities, and perform a pertinent neurologic examination. This includes mental status, sensory and motor function, and reflex integrity. Evaluation of the S2-4 reflexes using bulbocavernosus reflex and anal wink can help determine whether this pathway is intact, the absence may indicate sacral nerve disease. In females, determination of the pelvic floor strength and bimanual examination is performed to assess the neurologic system.

Routine office investigations include a 72-hour voiding diary (Fig. 12.1). This records the date, time, and volume of each void. In addition, each incontinent episode is recorded by the amount and the precipitating cause. This is very important to gauge the magnitude and frequency of incontinence, the overall voiding pattern, and the daily urine output, and estimates a functional bladder capacity. If incontinence is present, we insist on pad weight measurement; this is the most accurate and objective measure of incontinence before any invasive treatment. In adult male patients, an American Urological Association (AUA) symptom score (Fig. 12.2) is also a useful screening and baseline tool for LUTS/benign prostatic hyperplasia (BPH). Noninvasive urodynamics (UDs) such as uroflow (Fig. 12.3), and postvoid residual (PVR) are used routinely in our clinic. The uroflow by itself, although it cannot actually determine the etiology of abnormal voiding (some classic patterns are seen however; Figs. 12.4 and 12.5), serves as an excellent screening tool to determine whether further, more invasive testing is needed.19 In most patients without symptoms, a normal uroflow study and the absence of residual urine on ultrasonography are sufficient to rule out significant bladder dysfunction. Abnormal uroflow patterns or incomplete bladder emptying may be situational and should be repeated.20,21 Routine laboratory investigations (in addition to transplant workup) include urine analysis (UA) and culture. If hematuria or sterile pyuria is detected, this will lead to more invasive investigations with cystoscopy (discussed next). 

INDICATIONS FOR INVASIVE INVESTIGATIONS Invasive UDs with fluoroscopy (videourodynamics, VUDs) are a useful test for evaluating patients with LUTD. Some uncomplicated patients may not need these after the noninvasive investigations have been completed. The AUA has published guidelines on UDs and states that VUDs should be strongly considered in all NGB patients in the face of pending invasive surgical treatment.22 In nonneurogenic patients with suspected detrusor overactivity (DO), abnormalities of filling and storage, and bladder outlet obstruction, UDs may be performed. This can be helpful when there is a diagnostic dilemma, symptoms do not correlate with objective findings, and when considering irreversible invasive therapy. Our VUDs protocol includes cystometry and electromyography of the pelvic floor when the bladder capacity and compliance are questionable, the uroflow pattern is abnormal, or there is a history of bladder neck or outlet dysfunction. The use of fluoroscopy can also be valuable in helping determine the etiology of the voiding dysfunction. Cystoscopy is indicated in patients who demonstrate hematuria, sterile pyuria, and difficulty catheterizing or other indications of anatomic urethral or bladder abnormality. Patients who have had a prior augmentation cystoplasty or any other questionable surgeries should also undergo pretransplant cystoscopy to rule out stones, foreign bodies, lesions, and possible tumors

12 • Transplantation and the Abnormal Bladder

Time

Amount Leak Volume Activity During Urge? Voided (in cc’s 1 = Drop/Damp Leak (Yes/No) or Ounces) 2 = Wet 3 = Bladder Emptied

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Fluid Intake (Amount in Ounces/Type)

Fig. 12.1  An example of a 24-hour voiding diary; patients are asked to complete this over 3 days. (Reproduced with permission from Springer, Practical Urodynamics for the Clinician, page 24.)

that may arise in these situations. It is the gold standard test to rule out pathology of the bladder and urethra. It is also of some benefit in those with bladder outlet obstruction and also provides information on the urethral sphincter. 

PRETRANSPLANT IMAGING In addition to a screening ultrasound of the native kidneys performed in all transplant candidates, further imaging may be needed. In the case of hematuria and sterile pyuria, routine imaging of the upper urinary tract is indicated with contrast computed tomography (CT) with a delayed protocol to opacify the native collecting system. In cases where there is not enough renal function to opacify the collecting system, patients may need to undergo cystoscopy with evaluation of the collecting system by the use of retrograde pyelograms. If a previously unknown neurologic condition is suspected, investigation with magnetic resonance imaging (MRI) of the brain and spinal cord may be necessary to evaluate the central nervous system for possible etiology.

After the evaluation is completed, one can make a judgment as to the adequacy of the lower urinary tract. Criteria for a usable bladder relate to bladder capacity, bladder compliance, the bladder’s ability to empty completely, and urinary continence. The presence of vesicoureteral reflux also should be taken into consideration. Errando et al. found it necessary to perform UDs in 6.9% of 475 transplant recipients based on the following indications: (1) the presence of lower urinary tract symptoms as outlined by history and patient reported outcome surveys, (2) the presence of a defunctionalized bladder in the anuric patient, and (3) the presence of a complex urologic history where the diagnosis cannot be made on history alone. These investigators found that 45% of the evaluated patients had abnormal urodynamic studies.23 However, defunctionalized bladders that were normal before the onset of anuria, as a rule, recover function after diuresis is restored without specific management.20 In some cases of LUTD, a voiding cystourethrogram (VCUG) is useful to estimate bladder capacity and to outline its contour, and it may be performed at the same time as UDs when fluoroscopy is used. It is also essential to evaluate

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AUA SYMPTOM SCORE (AUASS) PATIENT NAME: ___________________________ (Circle One Number on Each Line) Over the past month or so, how often have you had a sensation of not emptying your bladder completely after you finished urinating?

Not at All

TODAY’S DATE: _____________

Less Less Than About More Almost Than 1 Half the Half the Than Half Always Time in 5 Time Time the Time

0

1

2

3

4

5

During the past month or so, how often have you had to urinate again less than two hours after you finished urinating?

0

1

2

3

4

5

During the past month or so, how often have you found you stopped and started again several times when you urinated?

0

1

2

3

4

5

During the past month or so, how often have you found it difficult to postpone urination?

0

1

2

3

4

5

During the past month or so, how often have you had a weak urinary stream?

0

1

2

3

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5

During the past month or so, how often have you had to push or strain to begin urination?

0

1

2

3

4

5

None

1 Time

2 Times

0

1

2

Over the past month, how many times per night did you most typically get up to urinate from the time you went to bed at night until the time you got up in the morning?

3 Times 4 Times

3

4

5 or More Times

5

TOTAL: _____________

Add the score for each number above and write the total in the space to the right. SYMPTOM SCORE: 1–7 (Mild) 8–19 (Moderate) 20–35 (Severe) QUALITY OF LIFE (QOL) Delighted Pleased

How would you feel if you had to live with your urinary condition the way it is now, no better, no worse, for the rest of your life?

0

1

Mostly Mixed Mostly Unhappy Terrible Satisfied Dissatisfied

2

3

4

5

6

Fig. 12.2  The American Urology Association symptom score, also known as the International Prostate Symptom Score (IPSS).

12 • Transplantation and the Abnormal Bladder

urethral anatomy and to determine the presence of vesicoureteral reflux when that information is necessary. Ramirez et  al. retrospectively looked at 271 pediatric renal transplantations and found VCUG useful in children less than 8 years of age and those with a history of urologic disease,18 whereas in adults without a history of urologic disease or symptoms VCUG is not necessary.24 

NORMAL CYSTOMETRIC VALUES Bladder capacity varies with age. Known formulae exist to determine whether the bladder capacity for age is

Volume (mL)

Normal Curve Maximum flow rate

Voided volume Time to maximum flow

Average flow rate

Time (s)

Flow time Fig. 12.3  Illustration of a normal uro-flow curve, continuous and bell shaped with a tail; Qmax is reached in the first third and final phase and shows a rapid decrease and a sharp cutoff at the end. (Reproduced with permission from Springer, Practical Urodynamics for the Clinician, page 36.)

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satisfactory for a given patient. With the capacity of the newborn bladder at about 30 mL, and bladder capacity increasing by about 30 mL each year almost until puberty,21 the formula (age in years + 1) × 30 = bladder capacity in mL is useful. For infants we prefer the estimation of 7 mL/kg.25 Although most calculations use the patient’s age, assuming that the body habitus is within normal limits, this is often not the case in patients with spina bifida and ESRD. In this population we prefer the formula mentioned earlier, which assumes 7 mL of capacity for every kg of body weight. The presence of a lower than expected bladder capacity on a preoperative evaluation should serve as an indication for more involved testing and referral to a urologist. Bladder compliance is defined as the change in bladder pressure for a given change in volume. It is calculated by dividing the volume change (ΔV) by the change in detrusor pressure (ΔPdet)—compliance ΔV/ΔP detrusor—and is expressed in mL/cmH2O. Decreased bladder compliance implies a poorly distensible bladder in which the pressure/volume curve is steep, and the pressure rise is rapid for low-volume increases. Although numerical values are often used to express compliance, interpretation of these numbers must take into consideration age and expected bladder capacity. The lowest full resting pressure is preferable regardless of the maximal bladder capacity. Normal compliance is thought by most experts to be greater than 12 mL/cmH2O. Transplantation into a small, low compliant bladder is possible, as demonstrated by a report on 13 patients transplanted into small

Continuous Flow Curves

A

B

C

D

Fig. 12.4  Abnormal continuous flow curves; (A) compressive (benign prostatic obstruction); (B) constrictive flow curve (urethral stricture); (C) idiopathic detrusor overactivity; (D) detrusor underactivity. (Reproduced with permission from Springer, Practical Urodynamics for the Clinician, page 36.)

Intermittent Flow Curves

A

B

Fig. 12.5  Abnormal intermittent flow curves; (A) detrusor sphincter dyssynergia; (B) Valsalva voiding curve: patients with areflexic or hypocontractile bladder void with valsalva maneuver that is represented as an intermittent and irregular curve. (Reproduced with permission from Springer, Practical Urodynamics for the Clinician, page 37.)

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bladders that had been defunctionalized for 3 to 20 years but not augmented (three PUVs). A graft survival of 62% at 4 years was seen.26 

Special Pretransplant Issues METHODS TO ENHANCE BLADDER EMPTYING Periodic, complete emptying of the bladder is important to prevent infections, keep the intravesical pressure low, and allow for urinary continence. Chronic urinary retention may lead to overflow incontinence and urinary tract infection (UTI). When intravesical pressures are high, hydronephrosis with or without vesicoureteral reflux and renal damage may develop. McGuire and associates27 stated that sustained detrusor pressures greater than 40 cmH2O can cause upper tract damage. Medications that relax the bladder neck musculature, such as alpha blockers, may be used but are of unproven effectiveness in patients with neuropathic voiding dysfunction (NVD) or PUV.28,29 Symptomatic improvement of lower urinary tract symptoms in adults has been documented.30,31 Botulinum A toxin injection to the sphincter mechanisms may be effective to improve bladder emptying in high spinal cord lesions but the effect is short-lived.32 Therefore in most cases of incomplete bladder emptying, clean intermittent catheterization may be necessary and provides a safe way to manage bladders that otherwise cannot function on their own.33 This is also true for renal transplant patients.34 

VESICOURETERAL REFLUX AND ABNORMAL BLADDER COMPLIANCE In nonneurogenic patients, the presence of vesicoureteral reflux (VUR) without LUTD may not necessarily put the graft at risk. However, when voiding dysfunction exists, VUR in an immunocompromised patient may lead to renal infections and other complications. Hence when preoperative VUR exists, a complete evaluation is warranted. This includes VUDs to rule out bladder outlet issues and loss of compliance. If severe reflux is identified in a neuropathic setting and is thought to be from poor compliance or high-pressure voiding, then augmentation may need to be performed preoperatively to produce a low capacity safe bladder reservoir. High-grade vesicoureteral reflux that is left untreated after transplantation is often accompanied by a higher risk of UTIs, even if it was not a problem before transplantation.35 Surgical options for treatment of VUR—with ureteral reimplantation or nephrectomy—have been associated with a reduced risk of infection after transplantation.36 A typical case is that of a boy with PUV with renal insufficiency and bilateral high-grade reflux. If there are no febrile UTIs, the best course of action is to wait until the time for transplantation is near. Nephrectomy either before transplant or at the time of transplant may be necessary to prevent recurrent infections and is at the discretion of the transplant surgeon.37 There are many possible causes that decrease compliance of the bladder. A previously normal defunctionalized bladder because of anuria or supravesical diversion may be small but usually returns to normal capacity and

compliance after refunctionalization by undiversion or transplantation. Cycling such bladders before transplantation is uncomfortable for the patient and unnecessary, and we no longer recommend this practice.38 A bladder may be anatomically small, as is often the case in patients with a history of bladder exstrophy or epispadias. A small bladder per se is not a threat to the upper tracts as long as the patient is incontinent and compliance is safe. However, when bladder outlet resistance has previously been surgically increased in an attempt to achieve continence, high intravesical pressure and hydronephrosis may ensue. Such bladders may require reconstruction with bladder augmentation or other aggressive therapies to improve their storage ability to safely accept a transplant kidney. Patients with neurogenic LUTD may have anatomically normal but functionally small bladder capacity at safe pressures. Some cases of low-volume and poor compliance may respond well to oral antimuscarinic medications or botulinum A toxin injected in the detrusor. Antimuscarinic drugs, although not without potential side effects, can be effective and well tolerated for long periods of time and thus should be tried before surgical augmentation. Botulinum toxin injections, on the other hand, have a limited and temporary effect and are impractical for long-term management.39 Both of these methods can only be effective when the cause of the decreased compliance lies in the detrusor. Surgical augmentation of bladder capacity with its consequent improvement in compliance is normally accomplished by adding a reconfigured intestinal segment to the existing bladder. The majority of patients, particularly those with NGB, will require intermittent catheterization to empty the reconstructed bladder. For patients without a bladder, an incontinent diversion such as an ileal or colonic conduit can be constructed either before the transplant or at the time of transplant. With current improved immunosuppressive drugs, it is feasible to perform an ileal conduit in patients who are already established on immunosuppression therapy or at the same time as graft implantation.40–42 Success of transplantation into such conduits is good and well documented.43,44 A continent urinary reservoir can also be used to avoid an incontinent stoma.45 

TIMING OF BLADDER RECONSTRUCTION AND “DRY-DIVERSION” The timing and type of bladder augmentation relative to the transplantation warrant comment. This can be a topic of contention; one argument is that healing of bowel anastomoses and incisions may be adversely affected by the immunosuppressive status. Historically most authors have performed the augmentation or urinary diversion with ileal or ileocecal segment before transplantation.46–48 This provides an optimal environment for transplantation and familiarity with the diversion. On the other hand, some have argued for a delay in reconstruction where it is possible for stabilization of renal function after successful transplantation.49,50 There is no randomized evidence, and reconstruction before transplantation seems to be a safe approach, but it presents a management problem when the patient is anuric. In those expecting a cadaver donor, the bladder or neobladder must be kept sterile, so as not to miss possible opportunities to use a well-matched organ. We usually

12 • Transplantation and the Abnormal Bladder

recommend daily bladder irrigations and instillation of an antibiotic solution. Instillation of aminoglycosides, which is usually safe in patients with normal renal function, may lead to complications in patients with ESRD.51 The small number of cases in which the bladder was augmented after transplantation attests to the feasibility of such an approach when needed.52 Recent case reports show that it is also feasible to perform ileal conduit diversion simultaneously at transplantation40,53 avoiding the dry-diversion scenario, reoperation, and the complications associated with the staged approach. Nevertheless, until there have been further studies on this issue, it is generally recommended that if a conduit or a bladder augmentation is needed, it should be done several weeks before transplantation. 

Posttransplant Issues MAINTENANCE OF LOWER URINARY FUNCTION In all pediatric patients or adults who had prior LUTD, regular evaluation by a urologist is recommended to ensure ongoing safe lower tract function and prolonged graft survival. In addition, any new issues such as UTI in the immunocompromised setting can be addressed. Evaluation includes an interval history, patient reported outcome measures such as the AUA symptom score, bladder diary, examination and uroflowmetry (see Figs. 12.3–12.5), and residual measures when indicated. Care is usually coordinated with the nephrologist so that any new issues can be addressed in a multidisciplinary setting.

Urinary Tract Infections In patients with bowel interposition into the urinary tract, the urinary tract will be colonized by bacteria. In the immunocompromised setting, UTIs are one of the most common and bothersome long-term issues. Asymptomatic bacteriuria does not need treatment, although formation of stones needs to be carefully monitored because urease splitting organisms may reside. We recommend annual imaging of the urinary tract to look for bladder or upper-tract stones if there has been a history of stones. Symptomatic UTIs are

A

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commonly seen in transplantation into abnormal bladders.54 The use of prophylactic single-dose antibiotic in the first 6 months after transplantation does reduce the incidence of UTI by half.55 In those with recurrent UTIs, imaging to evaluate for stones in the entire urinary tract, including native kidneys, in addition to cystoscopy of the bladder or reservoir is indicated. Mucus production from ileum or colon bowel mucosa occurs equally and is normal. Mucus can be dealt with by daily irrigation with saline and the use of alkalizers if needed. 

Methods to Achieve Continence Some patients with bladder abnormalities such as NGB and PUV when associated with ESRD may also suffer from urinary incontinence. In general urinary incontinence can be caused by: (1) failure of the bladder to empty (overflow incontinence); (2) failure to store urine at low pressure; (3) incompetence of the sphincter mechanisms (stress urinary incontinence); (4) urgency incontinence; and (5) rarely, bypass of the sphincter complex (such as ectopic ureters, fistulae). Frequently more than one factor is present. The history, imaging studies, and urodynamic evaluation are essential to establish the pathophysiology of incontinence in a given patient. Overflow incontinence is managed by removal of the obstruction or, when the cause is failure of detrusor contractility, intermittent catheterization. The management of poor capacity and compliance was discussed in the previous section. The management of sphincter failure requires simultaneous attention to the storage capacity of the bladder. In the authors’ experience, injection of bulking agents in the bladder neck or proximal urethra has only a secondary role in enhancing continence and seldom achieves satisfactory results in cases of neuropathic sphincter failure. Numerous procedures have been described in an attempt to “reconstruct” the bladder neck. With the possible exception of occasional success in cases of bladder exstrophy, we have been disappointed with the results of such procedures for neuropathic incontinence in the adult and have abandoned their use. Implantation of an artificial urinary sphincter (AUS) is effective as an initial option to manage sphincter incompetence (Fig. 12.6) and can be implanted at the bladder neck or the bulbar urethra. The AUS has become

B

Fig. 12.6  (A) The AMS-800 artificial urinary sphincter: It consists of a cuff implanted around the bulbar urethra, a pressure regulating balloon, and a pump that is positioned in the scrotum or labium major. (B) The plain radiograph shows components of the AMS-800—that contains contrast media within the system allowing troubleshooting of the device.

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the gold standard for treatment of incontinence associated with sphincter function loss.56 The current model (AMS 800, Boston Scientific, Boston, MA) was introduced in 1983 and has by and large remained unchanged to this day. Experience associated with the AMS-800 is therefore very high and 80% continence rates have been reported from numerous centers.57 In addition, the compatibility of the AUS with renal transplantation is well established. Revisions of the device may be needed for device malfunction, waning incontinence, infection, and urethral cuff erosion.56 These secondary procedures and salvage operations are associated with comparable outcomes compared with primary surgery.58 In carefully selected patients, the use of the male transobturator sling has comparable outcomes compared with the AUS.59 In females, aponeurotic slings created with the patient’s rectus fascia or other off-the-shelf biological materials (cadaveric fascia lata, porcine intestinal submucosa) are effective for those dependent on intermittent catheterization who have excellent bladder capacity and compliance (Fig. 12.7). 

Results of Renal Transplantation into Reconstructed and Abnormal Bladders Transplantation can be performed safely in patients with reconstructed bladders and urinary diversions with acceptable graft survival and function. Whereas some authors report an increased incidence of urologic complications, such as urinary leak, ureteral stenosis, symptomatic UTIs, metabolic acidosis, and calculi, there are few controlled studies that permit meaningful comparisons between results of transplantation in native versus reconstructed bladders. Comparison among reported series is difficult because some fail to define the source of the graft, which is one of the best-known determinants of graft survival. Some series combine patients with bladder

Fig. 12.7  Fluoroscopic image of voiding cystometrogram during urodynamics in an adult patient with a valve bladder, dilated posterior urethra, and cone-shaped bladder.

augmentation with patients with diversions; this is problematic because it is well recognized that nonrefluxing ureteroenterostomies, in contrast to ureteroneocystostomies, carry a risk of stenosis of greater than 10%.60 Nevertheless, one retrospective controlled study that included mostly adult patients with urinary diversion failed to show any differences with control patients with normal bladders.61 Most authors agree that, although more complicated, it is feasible to proceed with renal transplantation in patients who are known to have an abnormal bladder with good results in both adult62,63 and pediatric and transition patients.33,44,47,64–69 

Special Considerations for the Transplant Surgeon POSTERIOR URETHRAL VALVES Renal transplantation in patients with a history of PUV presents unique challenges. Some of these patients have bladder dysfunction (see Fig. 12.5) with poor compliance,70,71 and the proportion may be higher in those who have renal failure. Although many uncontrolled studies suggest that renal transplantation into the valve bladder is associated with good results,72,73 close examination of every controlled study reported to date indicates that patients with renal transplantation into nonreconstructed valve bladders exhibit higher creatinine levels at the end of 5 years compared with controls. This higher creatinine level has been observed in virtually all studies reported and has been attributed to bladder dysfunction.6,7,74,75 Salomon and colleagues76 reported worse results of transplantation in children with PUVs and symptomatic bladder dysfunction73 than in children without such symptoms. The graft survival may be normal or marginally decreased in these cases.77 Therefore it has been tempting to pursue an aggressive approach to the valve bladder in hopes of improving the lifespan of the native kidneys and the results of renal transplantation. However, others78 have shown that patients with PUVs managed by a limited intervention approach had better outcomes than patients who underwent extensive urologic procedures. Nonetheless, transplantation into a nonreconstructed valve bladder and into an augmented bladder can yield acceptable graft survival rates.28 With the lack of controlled studies of patients with PUVs to define the possible advantages and risks of lower urinary tract reconstruction, no recommendations can be made based on the available evidence as to the indications of bladder augmentation in this condition. In addition, one study indicates that the rate of posttransplantation UTIs is greater in patients with a history of PUV, regardless of the presence of reflux.6 This information is important, not to discourage renal transplantation in young patients with a history of PUV, but rather to pay particular attention to bladder care in these cases. It would seem rational to do everything feasible to optimize bladder function before transplantation by improving emptying, decreasing storage pressures, and providing adequate capacity. When evaluating these bladders, it must be remembered that what is considered adequate bladder

12 • Transplantation and the Abnormal Bladder

capacity and compliance varies with the obligatory diuresis of a given patient. Inadequate capacity in a polyuric child with ESRD may become acceptable after the transplant when the urine output normalizes. 

PRUNE-BELLY SYNDROME Renal failure develops in a significant number of patients born with PBS. The causes are renal dysplasia, obstruction, and pyelonephritis.4 The first renal transplant in a patient with PBS was reported in 1976 by Shenasky and Whelchel,79 followed by other single-case reports. In 1989 Reinberg and colleagues reported on a series of children with PBS that were transplanted, with results similar to those of a control group.80 These results were confirmed by Fontaine and colleagues68 in 1997. This is not surprising because bladder storage pressures are low in most cases of this syndrome. Later, an Italian group published their experience with a series of five boys and reported good results as well, but they stressed the need to address the lack of abdominal wall musculature by performing abdominal wall reconstruction in selected patients.81 A unique complication specific to renal transplantation performed in patients with PBS is torsion of the graft. Whether this complication occurred because of the lax abdominal musculature or the fact that the kidney was grafted intraperitoneally is not clear.82,83 

MALE VOIDING DYSFUNCTION, BPH/LUTS There are some special scenarios that warrant attention. The mean age of transplant recipients is increasing in the US as a result of improvement in care.84 In addition, because a greater number of older men are undergoing renal transplantation there are more issues with BPH. BPH is a chronic age-related condition and may lead to bladder outlet obstruction (BOO) and associated LUTS. The incidence of BPH/LUTS in this group may be masked in the pretransplant population because of decreased or absence of diuresis. Adult male transplant recipients with BPH and LUTS should be treated medically similarly to their healthier counterparts. With regard to invasive surgical treatment, special considerations need to be taken into account. The gold standard outlet procedure is a transurethral resection of the prostate (TURP), and the perioperative surgical risks need to be carefully balanced. Those who are in active renal replacement therapy have chronic uremia-associated platelet dysfunction, higher cardiovascular risk, and electrolyte and fluid imbalances, which increase the risk of the procedure. In addition, those who produce minimal or low volumes (<500 mL/day) of urine may be at additional risk from low volume flow through the urethra in the postoperative phase. These include poor healing and stricture and scar formation from a “dry” TURP cavity. Despite the immunocompromised state, posttransplant TURP is safe when indicated as the patient is metabolically optimized and overall cardiovascular risks improved. When performed at 6 months after transplantation, TURP has excellent safety and outcome profile and is durable.85 When TURP is performed less than 60 days after transplantation, the incidence of UTI and loss of renal function is increased.86 Hence our approach is to perform a staged TURP once the

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patient has progressed to 6 months posttransplant, allowing improvements in functional bladder capacity and metabolic anomalies. 

FEMALE VOIDING DYSFUNCTION Common causes of bladder outlet obstruction and voiding dysfunction in adult females include severe organ prolapse and prior incontinence surgery. Functional bladder outlet obstruction and detrusor underactivity are also prevalent in women. The AUA symptom score has been shown to be a poor screening tool for defining severity of bladder function in women with LUTS.87 Given the fact that no standard definition for BOO exists in females and screening uroflowmetry has limitations in recipient females, VUDs is the gold standard in diagnosis of female voiding dysfunction when associated with pelvic floor abnormalities. Pelvic organ prolapse management and incontinence surgery with synthetic mesh in transplant recipients improves quality of life and is feasible.88,89 Our approach is the same as in nontransplant patients, although we reserve all operative procedures for at least 6 months after renal transplantation. 

Conclusion ESRD caused by congenital genitourinary anomalies is common, especially in pediatric patients. Furthermore, lower urinary tract dysfunction is seen frequently in adult transplant candidates and recipients. Integrity of the lower urinary tract is mandatory before transplantation, and proper investigation should be done in selected patients, ideally by a urologic specialist. Graft implantation into the native bladder is always preferred. If the bladder is unsuitable, planning a multidisciplinary approach is advocated, and staged reconstitution of the lower urinary tract is feasible. Bladder reconstruction may be done at the time of transplant or prior when clinically feasible. Although not exempt from complications, reconstruction is an acceptable method for patients with an abnormal lower urinary tract who are candidates for renal transplantation. Posttransplant monitoring of LUTS by a urologic specialist is mandatory because procedures to correct incontinence, voiding dysfunction, and bladder outlet obstruction have excellent results in transplant recipients. Finally, even if the reported series of renal transplantation into abnormal bladders are small, the graft and patient survival rates in most series seem to be comparable to the rates for transplants into nonreconstructed bladders.

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