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J. D. Chamberlin et al.

136

managed conservatively [54, 57]. Rarely, surgical
intervention is indicated for recurrent pyelonephritis, in cases where LUT dysfunction has been
ruled out or controlled.
The presence of persistent unilateral reflux
into a dysplastic nonfunctioning kidney in males
with PUV, referred to as posterior urethral valve,
unilateral vesicoureteral reflux and renal dysplasia (VURD) syndrome, has been associated with
a better kidney functional prognosis than what is
experienced by standard PUV patients in the
short term [55, 58, 59]. The dysplastic kidney is
thought to provide a protective effect as the renal
pelvis and ureter absorb the high pressures generated by the bladder during voiding. Despite this
protective effect, up to 50% of patients with
VURD may develop some kidney scarring, voiding dysfunction, UTI, diurnal incontinence, and
long-term hydroureteronephrosis [58]. Therefore,
every boy with PUV, regardless of the presence
of favorable prognostic features, should have
close multidisciplinary team follow-up to identify and appropriately treat potential risk factors
to the remaining kidney function.
When necessary, kidney transplantation is
successful in patients with PUV with proper evaluation of the bladder for storage and emptying
[60]. Vesicostomy or bladder augmentation may
be needed in some PUV patients prior to kidney
transplant. Patients with PUV are at a higher UTI
risk after kidney transplantation [61].
a

Vesicoureteral Reflux
in the Pediatric Dialysis Patient
Reflux nephropathy is kidney damage or abnormal kidney development related to VUR.  The
kidney damage may be congenital or acquired
from repeated insults. Congenital sources of
reflux nephropathy represent renal dysplasia that
coexists with reflux rather than being directly
caused by it (Fig. 10.5). Subsequently, postnatal
kidney function may be worsened by pyelonephritis, which is facilitated by the reflux of
infected urine into the abnormal kidney unit [62–
65]. Differentiation between primary and secondary reflux has important therapeutic implications.
Primary VUR is reflux, which occurs in the
absence of secondary functional or anatomical
causes, such as PUV, ureteroceles, or neurogenic
bladder. Secondary reflux is associated with
transmission of high bladder pressures to the
upper tracts, which can further compromise the
kidney parenchyma. This section will cover primary VUR, while secondary VUR is discussed
under the specific primary conditions.
Primary VUR accounts for 7–25% of pediatric
CKD cases [6, 66, 67]. Over half of children with
VUR and CKD may require renal replacement
therapy by the age of 20  years, suggesting that
they have a relatively poor kidney prognosis and
deserve particular attention [68]. Neither medical
nor surgical management can alter the function of

b

Fig. 10.5  Findings suggestive of renal dysplasia: (a) bilateral high-grade reflux detected in infant without a history of

urinary tract infections; (b) DMSA scan demonstrates poor function of the left kidney moiety and photopenic defects


10  Urological Issues in Pediatric Dialysis

a dysplastic kidney, and treatment should therefore concentrate on preventing further UTI and
kidney damage by early diagnosis and treatment
of a febrile UTI (pyelonephritis) and correction
of bladder and bowel dysfunction. Medical treatment may involve increased fluid intake, constipation management, biofeedback, bladder
training, and prophylactic antibiotics.
Increased fluid intake allows for more urine
production. This, in turn, increases the volume
and frequency of voiding, effectively flushing the
LUT and mechanically clearing out bacteria.
Prophylactic antibiotics have long been held as
the cornerstone of conservative management of
VUR [69]. Recent large series have begun to
question this conventional wisdom [70–73].
Selective use of antibiotics based on UTI risk factors is a reasonable approach.
Bladder training is helpful for children with an
element of dysfunctional voiding. The process
involves the education and retraining of the voiding process to achieve volitional, regular, and
complete bladder emptying. Emphasis is placed
on the awareness of the pelvic musculature and
coordination of the detrusor muscle contraction
with sphincter relaxation.
This training can be enhanced by biofeedback
technology that registers and rewards the correct
identification and control of pelvic musculature.
The effective elimination of urine is very closely

tied to the effective elimination of feces, i.e.,
bladder and bowel dysfunction. Active management of constipation has been shown to improve
voiding dysfunction, incontinence, enuresis,
urgency, and UTI frequency [74–76].
The surgical approach to the child with VUR
and recurrent pyelonephritis who fails to respond
to medical management is usually a graded escalation in intervention, which includes circumcision in males, endoscopic sub-ureteric injection
of a bulking agent such as dextranomer/hyaluronic acid, and ureteral reimplantation. Although
surgical reimplantation is more invasive than
endoscopic therapy, it carries a higher overall
success rate in terms of reflux correction and a
lower future reflux recurrence rate. This is an
important distinction when considering the child
with borderline kidney function and a predisposi-

137

tion to recurrent, scarring UTIs. These patients
may benefit from a more aggressive approach,
consisting of early prophylactic circumcision and
surgical reimplantation of the ureter.
As for the reflux patient with CKD who
requires dialysis, the indications for medical
management or surgical intervention are essentially no different from those patients with normal kidney function. One must be aware that
once transplanted, these children will be immunosuppressed and have an additional kidney unit.
Following kidney transplantation, UTIs may
occur in children with VUR; approximately 60%
of these patients experience at least one episode
[77, 78]. The risk is highest in the first-year posttransplantation and then decreases over time
[79]. VUR is associated with acute pyelonephritis in patients with kidney transplants, but this

does not necessarily translate to kidney graft loss
[79–83]. Thus, due to the increased morbidity in
the setting of immunosuppression, proper evaluation should address pretransplant vesicoureteral
reflux, especially in patients with a history of
multiple episodes of pyelonephritis. In cases with
high-grade reflux and an associated poorly functioning kidney, performing a nephroureterectomy
rather than reimplantation should be considered.
Following kidney transplantation, VUR into
the allograft is common and varies according to
the ureteral implantation procedure used [79, 80,
84, 85]. As such, routine screening for VUR of
the transplant kidney is not recommended.
However, a VCUG is warranted to exclude reflux
into the native or transplanted kidneys in the setting of recurrent UTI posttransplant. Treatment
for posttransplant reflux-associated UTI is initially conservative. Patients who fail to improve
are candidates for surgical intervention. This may
involve efforts to stop the reflux or remove a
poorly functioning, refluxing native kidney unit.
Recently, the sub-ureteric injection of
dextranomer/hyaluronic acid has gained wide
­
acceptance as a minimally invasive method of
correcting VUR.  However, when compared to
open reimplantation of the ureters, the success
rate of ureteric injection is lower in both native
and transplant kidneys. Reported reflux resolution rates in the transplant kidney following ure-


138

teric injection are only 29–44% [86, 87].
Similarly, surgical reimplantation has reported
transient obstruction and a persistent increase in
serum creatinine in 60% of reimplanted children
[85]. Given the above issues, combined with the
efficacy of conservative management and the
concept that adult donor kidneys are less susceptible to the effects of refluxed bacteriuria, surgical intervention is rarely indicated in this patient
population.

J. D. Chamberlin et al.

rogenic voiding dysfunction difficult. As a result,
popular classifications tend to focus on the dysfunction rather than on the underlying cause [89].
Wein developed a clinical classification for
patients with urinary incontinence, dividing the
etiology into two broad categories: a failure of
storage and a failure of emptying [90]. Adequate
storage requires high bladder compliance, reasonable capacity, and the absence of detrusor
overactivity combined with adequate sphincteric
function. Efficient emptying requires a coordinated interaction of detrusor contraction and a
Neurogenic Voiding Dysfunction
lowering of the outlet resistance. Four broad,
simplified scenarios exist: (1) a bladder with adeUnder normal bladder circumstances, the detru- quate storage and an outlet with low resistance,
sor muscle and the sphincter complex function in (2) a bladder with adequate storage and an outlet
a coordinated fashion, which optimizes both with increased resistance, (3) a bladder with
urine storage and emptying. During the filling inadequate storage and an outlet with low resisphase, the detrusor muscle is relaxed and is com- tance, and (4) a bladder with inadequate storage
pliant, as it fills in volume without an increase in and an outlet with increased resistance (Fig. 10.6).
bladder pressure. As capacity is reached, the With this understanding, it is not uncommon for
intravesical pressure gradually rises. A full blad- the neurogenic bladder to be either incontinent,
der is detected by stretch receptors and perceived continent, or dyssynergic (i.e., lack of coordinain the central nervous system. During appropriate tion between detrusor muscle and bladder outlet,

voiding, the sphincteric mechanism relaxes in resulting in outlet occlusion in response to detruanticipation of a coordinated detrusor contrac- sor contraction leading to dangerously elevated
tion, expelling urine from the bladder. If voiding intravesical pressures).
needs to be delayed, afferent nerves stimulate
Regardless of detrusor compliance, poor tone
sympathetic and pudendal outflow activity, initi- in the sphincter mechanism typically results in
ating the guarding reflex, which inhibits detrusor urinary incontinence. However, as long as the
contraction and stimulates the rhabdosphincter to incontinence is associated with low leak point
increase outflow resistance [88]. Disrupted inner- pressures, there is little risk of damage to the
vation can lead to an alteration of this normal, upper tracts. In contrast, the “hostile bladder” is
coordinated interaction.
found in situations of a hyperreflexic, poorly
Neurogenic bladder dysfunction is an all-­ compliant, and small capacity bladder that is
encompassing term that describes vesicourethral combined with high outlet resistance. This resisunits with abnormal neural anatomy or function. tance is caused by sphincter hypertonia and
Neurological lesions vary considerably in their detrusor-sphincter dyssynergia. In these situainfluence on the key bladder functions of storage tions, high filling and voiding pressures are transand emptying. Upper motor neuron lesions tend mitted to the kidney, leading to kidney dysfunction
to produce a hyperreflexic bladder with sphincter and, if not corrected (especially if associated with
dyssynergia. Lower motor neuron lesions tend to UTI), permanent kidney damage [91].
produce an areflexic bladder with variable
Following the diagnosis of neurogenic voidsphincter function. Unfortunately, there are many ing dysfunction, initial management is directed at
neurological lesions that have various effects on maintaining acceptable bladder storage presthe detrusor muscle, the striated urethral sphinc- sures, ensuring efficient emptying, and preventter, and the smooth muscle of the bladder neck. ing UTIs [92]. Early medical management and
This high variability makes classification of neu- close monitoring are the cornerstones of a suc-


10  Urological Issues in Pediatric Dialysis

a

139

b

Compliant bladder

Poor sphincter tone

c

d

Compliant bladder

Increased sphincter tone

Fig. 10.6  The four broad scenarios based on bladder and
sphincter functionality: (a) good bladder compliance with
poor sphincter tone, (b) poor bladder compliance with

Small volume, poorly
compliant bladder

Upper tracts protected by
low outlet resistance

Small volume, poorly
compliant bladder

Upper tracts threatened by
high outlet resistance

poor sphincter tone, (c) good bladder compliance with
increased sphincter tone, (d) poor bladder compliance

with increased sphincter tone

Table 10.2  Basic concepts of management for neurogenic voiding dysfunction based on Wein’s classification [90]
Facilitate storage

Facilitate
emptying

Bladder
Decrease tone
 Bladder muscle relaxants
Increase capacity
 Bladder augment
Increase bladder pressure
 Trigger zones
 Bladder training

Outlet
Increase resistance
 
α-Agonists
 Mechanical compression

Bypass
CIC
Diversion

Decrease resistance
 
α-Blockade

 Sphincterotomy
 Bladder neck disruption
 Urethral dilation

CIC
Diversion


140

J. D. Chamberlin et al.

cessful outcome for these children. Patients vary tinent diversion, a safe and reliable method of
in their need for specific medical interventions decompressing the upper tracts in young children
but should be managed according to their unique with neurogenic bladders [103].
urodynamic dysfunction. The basic concepts of
When continence is the goal of treatment,
this management are outlined in Table 10.2. The bladder emptying aided by CIC through the uremajority of children with “hostile bladders” are thra is favored. In some children, this is not feamanaged with a combination of CIC to ensure sible, as catheterization may be anatomically
regular and complete emptying [93–95]; difficult or impossible (as seen in children with
­anticholinergics to attenuate neurogenic detrusor urethral strictures), poorly tolerated (in patients
overactivity, increase capacity, and decrease tone with a sensate urethra), or difficult to perform
[96, 97]; α-blockers to decrease the sphincter (related to body habitus and poor manual dextermuscle tone [98, 99]; and prophylactic antibiotics ity) [9]. These patients may benefit from a surgito prevent recurrent UTI.
cally constructed continent catheterizable
Surveillance is a crucial component of the channel, usually fashioned with the appendix
management of the neurologically impaired (Mitrofanoff channel) or reconfigured small
child. In myelodysplasia, the neurological conse- bowel (Monti channel) [104]. These conduits
quences are often dynamic, with changes taking should be as short and straight as possible, to
place throughout childhood but particularly at avoid catherization issues, and enter the bladder
puberty when linear growth is accelerated. The from an easily accessible, cosmetically approprientire urinary system should be screened regu- ate site. Accessibility is the principal goal and is
larly for evidence of deterioration. Ultrasound of ideally determined preoperatively by the surgeon,

the kidneys, ureter, and bladder is useful in patient, and a stoma nurse. Cosmesis is a seconddetecting kidney growth failure, scarring, loss of ary concern to function, often best achieved with
cortico-medullary differentiation, hydronephro- the stoma placed at the umbilicus (Fig. 10.7).
sis, bladder wall thickening, and significant
Surgical interventions that augment the bladresidual bladder volumes. In the patients who are der are aimed to improve compliance, increase
able to void, urinary flow rates may demonstrate capacity, and decrease uninhibited detrusor conabnormal flow curves and, combined with elec- tractions. Bladder augmentation with enterocystromyography, may demonstrate detrusor-­toplasty is the most commonly used technique,
sphincter dyssynergia. Urodynamic studies are
useful in monitoring bladder dynamics during the
filling and emptying phases. Spinal MRI is indicated for the initial workup of many of these
patients and may be indicated during the surveillance period when changing clinical features suggest the development of a potentially correctable
cause, such as a tethered spinal cord.
If the medical management is ineffective or
not tolerated, treatment will need to be escalated.
Surgical strategies are mainly aimed at addressing three different issues: decreasing bladder outlet resistance, providing alternative access for
catheterization, and enhancing bladder capacity
and compliance. For patients in whom continence is not necessary, strategies aimed at reducing outlet resistance include urethral dilation Fig. 10.7 Patient with an appendicovesicostomy
[100, 101] and sphincterotomy (in older male (Mitrofanoff channel), performing self-catheterization
patients) [102]. Vesicostomy produces an incon- through stoma located at the umbilicus


10  Urological Issues in Pediatric Dialysis

and it involves the use of a portion of the intestine
that has been detubularized, reconfigured into a
patch, and then sutured into the defect of a widely
incised bladder. The gastrointestinal patch can be
ileum or colon, but the most commonly used is
the ileum, due to its preferred absorptive and
secretory profile [105, 106]. Following enterocystoplasty, metabolic abnormalities may develop
over time, due to the exposure of intestinal epithelium, with its absorptive and secretory characteristics, to urine. This is more clinically relevant in
children with marginal kidney function.

To avoid the metabolic impact of the intestinal
augments, the bladder may be augmented using
tissue naturally lined by urothelium, such as the
ureter. While most urothelium-lined augmentations create only modest urodynamic improvement, the best improvement is seen with the use
of a dilated tortuous ureter of a poorly functioning kidney unit [107, 108]. While now uncommonly performed due to inferior results, an
auto-augmentation of the bladder was proposed
to excise the hypertrophied detrusor muscle, thus
creating a diverticulum of bladder mucosa
through the detrusor muscle, thereby increasing
compliance and capacity. A summary of the
advantages and disadvantages of common bladder augmentation procedures is provided in
Table 10.3.

 ladder Augmentation and End-­
B
Stage Kidney Disease
A severely dysfunctional bladder that has caused
or facilitated failure of the native kidneys will put
a transplanted kidney at risk. If this hostile environment is left untreated, a transplanted kidney
will fail. Prior to effective reconstruction of the
lower urinary tract to create a safe reservoir for
urine storage, severe bladder dysfunction was a
contraindication to kidney transplantation. This
has allowed for a successful kidney transplantation in children with stage 5 CKD and severe
LUT dysfunction.
The safety and timing of bladder augmentation in the child with ESKD in the context of kidney transplantation has been controversial

141
Table 10.3  A summary of the advantages and disadvantages of common augmentation procedures
Auto-augmentation

 Lined by urothelium
   No metabolic sequelae
   No bowel harvesting
  Extraperitoneal approach
    Not reliable at increasing bladder volume
Ureterocystoplasty
 Native ureter
 Lined by urothelium
   No metabolic sequelae
   No bowel harvesting
   Mucosa backed by muscle
   Not always available
   Not always sufficient
   Additional exposure required (laparoscopic/
open)
Colocystoplasty
 Sigmoid/ileocolic
  Large diameter
   Reliable blood supply
  Mobile segments
  Ileocecal valve can be used to prevent urinary
reflux
   Can be tunneled
   Not always available
    Can impact gut function
   Bowel surgery required
    Absorption of urinary waste
   Lifelong alkalinization required if kidney
function impaired
   Mucus production +++

    Bladder stone and UTI risks +++
   Higher perforation rate
   Tumor risk
Ileocystoplasty
 Preterminal ileum
   Reliable blood supply and length
   Most compliant bowel segment
   Hyperchloremic metabolic acidosis
   Mucus production ++
    Bladder stone and UTI risk ++
    Vitamin B12 deficiency
   Tumor risk

[109–117]. The cumulative graft survival rates
for children who underwent major LUT reconstruction seem favorable, despite the lack of
standardized follow-up between cohorts [111,
­
113, 114, 118]. The safety of transplantation in
patients with bladder augmentation has been
established; however, the timing of the reconstruction in relation to the timing of the kidney
transplant is debated. If bladder augmentation
occurs before transplantation, adequate capacity