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).

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.

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.

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.

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.

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.

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 /Δ 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.

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 associates stated that sustained detrusor pressures greater than 40 cmH ₂ O 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. Symptomatic improvement of lower urinary tract symptoms in adults has been documented. 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. 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. This is also true for renal transplant patients.

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.

Surgical options for treatment of VUR—with ureteral reimplantation or nephrectomy—have been associated with a reduced risk of infection after transplantation. 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.

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. 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. 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. Success of transplantation into such conduits is good and well documented. A continent urinary reservoir can also be used to avoid an incontinent stoma.

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. 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. 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 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. The small number of cases in which the bladder was augmented after transplantation attests to the feasibility of such an approach when needed.

Recent case reports show that it is also feasible to perform ileal conduit diversion simultaneously at transplantation 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.