EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Lower urinary tract abnormalities are difficult to resolve in pediatric kidney transplant patients. Measure of residual urine, voiding cystourethrography, retrograde urethrography, cystometry, electromyography of urethral external sphincter muscle, urethrometry, and uroflowmetry are the primary methods for evaluation of lower urinary tract abnormalities. Endoscopic resection or ablation of urethral valves is required in children with posterior urethral valve to treat obstruction, but bladder function does not always recover and may deteriorate to end-stage renal failure even after the obstruction is released. This bladder dysfunction in posterior urethral valve defines valve bladder syndrome. Vesicoureteral reflux caused by high vesical pressure can cause even worse renal graft function posttransplant. In our patient group, urinary diversion occurred with Mitrofanoff conduit using an appendix in 6 children, a Yang-Monti channel conduit using ileum in 1 patient, with cystostomy in 3 children, and with augmented cystoplasty in 9 children before or simultaneously with kidney transplant. These procedures should be selected based on the type of lower urinary tract abnormality including bladder function. Recently, we have preferred a continent diversion for self-catheterization in children with lower urinary tract abnormalities. We have conducted 9 augmented cystoplasty procedures using a portion of the sigmoid colon or ileum. Seventeen children retained their own bladders when the transplant ureter was implanted. Most patients needed clean intermittent catheterization, depending on the residual urine volume and a bladder function. Ten-year graft survival rate in kidney transplant in our department is 98% in 36 children with lower urinary tract abnormalities. Lower urinary tract abnormality is not always a risk factor for pediatric kidney transplant; however, a preoperative evaluation is important to choose the best option for urinary diversion.

Key words : Bladder function, Preoperative evaluation, Urinary diversion

Lower urinary tract abnormalities (LUTAs) can be divided into 2 groups: neurogenic bladders and lower urinary tract anomalies. A neurogenic bladder is caused by spina bifida,¹ anal atresia,² spiral cord injury or tumor, or cerebral palsy. Prune belly syndrome,³ persistent cloaca,⁴ and posterior or anterior urethral valve^5-7 all involve lower urinary tract anomalies.

Pretransplant evaluations of LUTAs are important, particularly for children with neurogenic bladdersand those unable to void through a native urethra. In this situation, a diversion or a conduit should be considered.

The Mitrofanoff conduit using an appendix is preferred to a simple diversion for kidney transplant.^8,9 It is easy for a parent or a child to manage the clean intermittent catheterization (CIC) required with the Mitrofanoff conduit. The Mitrofanoff conduit is advantageous for children because it can be kept dry and a urine storage bag is not required.

An augmentation cystoplasty for a neurogenic bladder with high pressure and small capacity is a good option for children with LUTA.¹⁰ A ureterocystostomy with an antireflux submucosal tunnel can be created easily in an augmented colon in which a submucosal layer is thicker than the ileum.

Here, we describe the challenging surgical techniques and skills required for children with LUTAs during kidney transplant and their kidney transplant outcomes.

Mitrofanoff Conduit
In our reported patient group, the Mitrofanoff conduit was used during kidney transplant in 7 children with LUTA from our department and from the Tokyo Metropolitan Children’s Hospital (Table 1). An appendix and a contralateral ureter were used as a conduit in 6 and 1 children, respectively (Figure 1 and Figure 2). As shown in Figure 1, the appendix was mobilized and separated from the cecum and placed in the retroperitoneal space, preserving the vascular pedicle. The one end of an appendix is introduced through a bladder submucosal tunnel and anastomosed with a bladder in an antireflux method to act as a continence mechanism (Figure 1 and Figure 2). The other end is passed through an opening in the umbilicus, and a catheter can pass to empty the bladder 4 to 6 times per day (Figure 3).

Case Presentations

Case 1
Case 1 was a 5-year-old boy who had a posterior urethral valve. At birth, he required a cystostomy for megalocystis and bilateral grade 5 reflux. At 3 months, a posterior urethral valve was diagnosed, and transurethral incision and resection of valves were performed (Figure 4).

His renal function gradually deteriorated; at 2 years of age, his serum creatinine value was 1.42 mg/dL. The Mitrofanoff conduit using an appendix was indicated, and the Mitrofanoff conduit and a living-donor kidney transplant were simultaneously performed. So far, the patient has had stable renal function with catheterization 6 to 7 times daily.

Case 2
Case 2 was a 6-year-old boy with anal atresia, hypoplastic kidneys, and a neurogenic bladder. A Mitrofanoff conduit was indicated for his neurogenic bladder. A right native ureter after right nephrectomy was used as a conduit (Figure 5). One end was anastomosed with the bladder using the antireflux method. The other end was placed in the skin orifice (Figure 5). Renal function has so far been stable with catheterization 2 to 4 times daily.

Case 3
Case 3 was a 6-year-old boy with posterior urethral valve. A Mitrofanoff conduit was indicated for a neurogenic bladder. A 2- to 2.5-cm segment of the ileum with a strip of mesentery was isolated from the distal ileum to serve as a conduit (the Spiral Yang-Monti channel; Figure 6).^11-13 The conduit was anastomosed with the bladder using the antireflux method, and an orifice of the conduit was made in the lower abdomen. Renal function has so far been stable with catheterization at 4 to 5 times per day.

Augmentation Cystoplasty
We treated 9 recipients with neurogenic bladders with augmentation cystoplasty. A cystoplasty using a sigmoid colon was performed in 5 kidney transplant recipients with meningocele, in 1 recipient with posterior urethral valve, in 1 recipient with spina bifida, and in 1 recipient with persistent cloaca (Table 1). A 30-cm-long segment of the colon was mobilized, preserving the mesentery (Figure 7).¹⁴ A seromuscular end-to-end anastomosis was made between the remaining oral and anal sides of the colon stump (Figure 7). The posterior wall of the colon pouch was created by side-to-side anastomosis of the opposed margins (Figure 7).

One patient with an anal atresia and a neurogenic bladder underwent an augmentation cystoplasty using an ileum. A 45-cm-long segment of an ileum cystostomy was mobilized, preserving the mesentery, and a seromuscular end-to-end anastomosis was made between the remaining oral and anal sides of the ileum stump (Figure 8). The longer ileum segments were sutured in a “W-shaped” configuration to each other to create an ileum pouch (Figure 8). The bladder was opened transversally to create an anastomosis site with a colon or an ileum pouch (Figure 9). A colon or an ileum pouch was sutured to the bladder remnant (Figure 9).

Outcomes
We conducted cystoplasty procedures in 9 children, Mitrofanoff in 7 children, and diversion (cystostomy) in 3 children from Kiyose Tokyo Metropolitan Childen’s Hospital from 1975 to 2009 and Toho University Omori Medical Center from 2005 to 2016. Seventeen children retained their own bladder during kidney transplant, despite presence of LUTA (Table 1), and CIC was performed from 2 to 6 times daily. Graft survival rates in children with LUTA (n = 36) and those without LUTA (n = 85) were 100% and 97% at 1 year, 98% and 97% at 5 years, and 98% and 92% at 10 years posttransplant, respectively (Figure 10), in our centers.

In the 2010 North American Pediatric Renal Trials and Collaborative Studies annual transplant report, causes of end-stage renal disease were classified into hypo/dysplastic kidney (15.8%), obstructive uropathy (15.3%), focal segmental glomerular sclerosis (11.7%), reflux nephropathy (5.2%), and others (52%).¹⁵ An obstructive uropathy and reflux nephropathy including LUTA and renal hypo/dysplastic kidney were accompanied by LUTA. Adams and associates reported that malformations of the lower urinary tract were the reasons for end-stage renal failure in 66 children (18.6%) among 349 pediatric kidney transplant patients.¹⁶ Lower urinary tract abnormalities also included neurogenic bladders due to meningocele.

Valve bladder syndrome is defined as persistent or progressive severe hydroureteronephrosis without residual or recurrent obstruction in patients with posterior urethral valve.¹⁷ Renal function can occasionally deteriorate even after ablation of posterior valves. A bladder overdistention due to a combination of polyuria, impaired bladder sensation, and residual urine volume can develop hydronephrosis and impair renal function.¹⁷ Therefore, a conduit or diversion with CIC is indicated to keep the bladder emptying in kidney transplant for children with the valve bladder syndrome.¹⁸ The Mitrofanoff conduit is an excellent surgical procedure and has an advantage as a continent diversion. It is also easy to introduce CIC posttransplant.^8,9 We mainly used an appendix as a conduit; however, we used an ileum with the spiral Yang-Monti channel method in one child.^11-13

Intravesical pressure should be controlled below approximately 35 to 40 cmH₂O under administration of anticholinergic drugs and catheterization.^19,20 An augmentation cystoplasty is indicated for children with small bladder capacity, low bladder compliance, and high intravesical pressure.¹⁰ An augmentation cystoplasty is a safe and effective option for children with end-stage renal disease undergoing kidney transplant. Recurrent urinary tract infection can occur posttransplant in children with an augmentation cystoplasty.²¹ It can also increase the risk of deterioration of renal graft function. Clean intermittent catheterization and antibiotic prophylaxis are important treatments to prevent urinary tract infection.

Reabsorption of ammonium chloride and ammonia and secretion of bicarbonate by the bowel can create an acid-base disturbance with augmentation cystoplasty, resulting in hyperchloremic metabolic acidosis.^21-23 Most patients who have augmentation cystoplasty require bicarbonate, resulting in a longer follow-up.²¹ Chronic metabolic acidosis could lead to depletion of calcium carbonate from bone, which may cause growth retardation in children.²¹

There is no significant increased risk of bladder cancer after bladder augmentation for a dysfunctional bladder.²⁴ However, patients with spina bifida are at risk for cancer regardless of whether augmentation is performed.

The graft survival rate of children with LUTA in our centers was 98% at 5 and 10 years posttransplant. Adams and associates reported that the graft survival rates in children with posterior urethral valve, Prune belly syndrome/VATER association, neurogenic bladder, and vesicoureteral reflux were 62.9%, 71.4%, 50%, and 78.5% at 5 years posttransplant, respectively.¹⁶ Kamal and associates reported that 5-year graft survival rate in living-donor kidney transplant in children with posterior urethral valve was 81%.⁶ Hatch and associates reported that 5- and 10-year graft survival rate in kidney transplant for 31 children with augmentation or diversion was 60%.²³ Our 5- and 10-year graft survival rates in kidney transplant for children with LUTA of 98% may be because we conduct pretransplant evaluations of LUTA, use appropriate indications for diversion including the Mitrofanoff conduit, and use augmentation cystoplasty and effective surgical skills.

Surgical challenges are present in pediatric kidney transplant patients with LUTA. The Mitrofanoff conduit, Yang-Monti channel, and augmentation cystoplasty are complicated urologic surgical techniques. A pediatric transplant surgeon should train and master the surgical skills necessary for LUTA. Proper care and successful surgery may promise better long-term outcomes of kidney transplant for children with LUTA.

Volume: 16 Issue: 1 March 2018 - Supplement - 1

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