Transplantation and the Abnormal Bladder


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.

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); 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 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 colleagues first pointed this out in 1988 for children with PUV, and since then other authors have verified these observations. Correction of structural anomalies and optimization of storage and emptying functions of the bladder are often recommended before transplantation. In fact, improvement of bladder function can slow down the progression of renal insufficiency and allow transplantation to be postponed. 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.

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.

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. 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. 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.

The pretransplant urologic evaluation aims to diagnose, treat, and optimize any preexisting LUTD. 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).

Fig. 12.1, An example of a 24-hour voiding diary; patients are asked to complete this over 3 days.

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

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. 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.

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

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

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.

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. 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 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. However, defunctionalized bladders that were normal before the onset of anuria, as a rule, recover function after diuresis is restored without specific management.

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 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, whereas in adults without a history of urologic disease or symptoms VCUG is not necessary.

Normal Cystometric Values

Bladder capacity varies with age. Known formulae exist to determine whether the bladder capacity for age is 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, the formula (age in years + 1) × 30 = bladder capacity in mL is useful. For infants we prefer the estimation of 7 mL/kg. 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 (Δ V ) by the change in detrusor pressure (Δ P det )—compliance Δ V P detrusor—and is expressed in mL/cmH 2 O. 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/cmH 2 O. Transplantation into a small, low compliant bladder is possible, as demonstrated by a report on 13 patients transplanted into small 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.

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