Chapter 104

Pediatric Genitourinary System

John M. Park and Julian Wan

Key Points

1 Embryonic kidneys develop from the intermediate mesoderm, with the definitive kidney forming as

result of inductive interaction between ureteric bud and metanephric mesenchyme. Paramesonephric

(müllerian) and mesonephric (wolffian) ducts contribute reproductive structures.

2 Multicystic dysplastic kidney (MCDK) is the most common form of congenital cystic disease. It

rarely causes any clinical problems and often involutes over time.

3 Ureteropelvic junction obstruction (UPJO) is the most common form of hydronephrosis detected in

utero.

4 Ureteral duplication is a common anomaly. Upper pole ureter can be associated with either

obstructing ureterocele or ectopic ureter, whereas lower pole ureter is more likely to be associated

with vesicoureteral reflux.

5 Vesicoureteral reflux (VUR) is an important problem to identify and manage in children who present

with urinary tract infection (UTI). VUR can lead to recurrent parenchymal renal infections, resulting

in renal scarring and other lifelong problems such as hypertension and pregnancy-related

complications.

6 Posterior urethral valve (PUV) is the most common congenital obstructive uropathy that leads to

end-stage renal failure and renal replacement therapy. When severe, it can lead to oligohydramnios,

renal failure, and pulmonary hypoplasia.

7 Hypospadias is common, occurring in 1 of 200 live births. In most cases, they are mild, presenting

with urethral opening near the distal shaft and glans. When associated with cryptorchidism, the

differential diagnostic possibilities must include disorders of sex development (intersex).

8 Undescended testicle occurs in 3% to 4% of full-term newborn males. If it remains ectopic beyond

age 1, surgical orchidopexy should be performed prior to age 2 to 3 to preserve future fertility

potential. When testicles are nonpalpable, laparoscopy is the gold standard to locate an

intraabdominal testicle or confirm testicular absence.

9 Prepubertal testicular tumors are benign unless associated with an elevated alpha-fetoprotein (AFP),

in which case yolk sac tumor should be suspected. Testicular sparing enucleation is appropriate for

mature teratomas.

10 Patients with neurogenic bladder disorders (such as spina bifida) must be evaluated with

urodynamic pressure–volume study to characterize its urine storage and emptying function.

Managing bladder pressure and emptying with clean intermittent catheterization (CIC) is paramount

to preserve renal health and improve quality of life.

1 FETAL DEVELOPMENT OF GENITOURINARY SYSTEM

Kidneys develop as paired intermediate mesodermal structures stretching craniocaudally along the

length of the abdomen. The embryonic kidneys, in order of their appearance, are pronephros,

mesonephros, and metanephros. Pronephros is nonfunctional and transitory in mammals. By the fifth

week, it is replaced by mesonephros. The mesonephros is thought to provide a transient excretory

function and also provides substrate for subsequent reproductive structures. The final step in renal

development is metanephros, which becomes the true functional kidney. It develops in the sacral region

as a result of inductive interaction between the ureteric buds (sprouting from the distal portion of

mesonephric ducts) and the condensing blastema of metanephric mesenchyme. The nephron, which

consists of glomerulus, proximal tubule, loop of Henle, and distal tubule, derives from the metanephric

mesenchyme, while the collecting system, consisting of collecting ducts, calyces, pelvis, and ureter, is

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formed from the ureteric bud. The kidneys ascend from their initial pelvic position to their final position

in the upper retroperitoneum. At fifth week, the terminal portion of the endoderm-lined yolk sac dilates

to become the cloaca. It is partitioned by the developing urorectal septum to form urogenital sinus

anteriorly (future vesicourethral canal and vaginal vestibule) and anorectal canal posteriorly. During the

fifth week, primordial germ cells migrate from the yolk sac to the posterior body wall near the

mesonephros to form the genital ridges. In males, under the influence of SRY (the sex-determining

region of the Y chromosome), primordial germ cells begin to differentiate into Sertoli cells, which then

drive the formation of testis cords and Leydig cells (responsible for producing androgen). In females,

the paramesonephric ducts (lying medially adjacent to the mesonephros; also known as the müllerian

ducts) develop into reproductive structures, namely upper vagina, uterus, and fallopian tubes. In males,

mesonephric ducts (known as the wolffian ducts) develop into vas deferens and epididymis under the

influence of androgen. The presence of müllerian inhibiting substance (MIS) produced by Sertoli cells of

a developing testicle causes müllerian ducts to regress in males. In females, in the absence of Sertoli and

Leydig cells, mesonephric (wolffian) ducts regress and müllerian ducts continue to develop into female

reproductive structures. Starting sixth week, under the influence of androgen and more importantly,

dihydrotestosterone (converted intracellularly by the enzyme 5-alpha reductase), the genital tubercle

elongates and the genital and urethral folds fuse in the midline to form scrotum, penis, and penile

urethra. The formation of distal glandular urethra occurs by a combination of urethral fold fusion

proximally and the ingrowth of ectodermal skin tag distally. Both developing testicles and ovaries move

to the pelvic location by the third month. In males, with androgen-influenced regression of cranial

suspensory ligament and swelling/contraction of gubernaculum, the testicles undergo inguino–scrotal

descent during the third trimester.

ANOMALIES OF THE KIDNEY

Renal anomalies can be categorized into several recognized variants in position, number, and shape.1

When the kidney does not move to the normal expected position, it is termed an ectopic kidney. A

kidney that fails to ascend and remains near the bladder becomes a pelvic kidney, thought to occur in 1

of 3,000. It can travel too far and rise above the ipsilateral diaphragm to become an intrathoracic kidney.

It can cross over to the other side and end up in a contralateral position as a crossed ectopic kidney.

Crossed renal ectopia occurs with renal parenchymal fusion in 90%. Unlike the more commonly

encountered ureteral duplication, crossed ectopic kidney’s ureter crosses over the midline and drains

into the bladder in the contralateral side. In 30% to 50%, ectopic kidneys can have varying degrees of

hydronephrosis and vesicoureteral reflux (VUR). Most ectopic kidneys are asymptomatic and clinically

insignificant, except in cases of associated ectopic ureter. The adrenal glands develop independently

from the kidney, and it should be in normal position beneath the diaphragm, even if the ipsilateral

kidney is ectopic. The possibility of an ectopic kidney must be entertained if a kidney is missing in the

usual location during an exploratory laparotomy.

The embryonic metanephros can become fused at their caudal ends. The most common form of this

anomaly is the horseshoe kidney, so named because the lower poles of the kidneys are linked either by a

fibrous band or a section of functional tissue. It has an incidence of 0.2%. Horseshoe kidneys are notable

for their low position in the body due to isthmus trapping by the inferior mesenteric artery. VUR and

ureteropelvic junction obstruction (UPJO) have been found in up to 50% of patients with a horseshoe

kidney.

In addition to anomalies of position and fusion, there can be an extra or supernumerary kidney. This

very rare finding is usually discovered incidentally and occurs because there is separation of the

metanephric blastema allowing a distinct kidney to develop. This should not be confused with a

duplicated system where there are two collecting system draining a single kidney.

Failure of the ureteric bud to form or join the metanephric mesenchyme will result in renal agenesis.

Bilateral renal agenesis is very rare and the infants with this condition are either stillborn or perish soon

after birth due to respiratory failure. The characteristic Potter face and the presence of severe

oligohydramnios are pathognomonic. When unilateral renal agenesis occurs, it is associated with a

variety of other genitourinary findings; about 50% will still have a vestigial ureter, and about 30% will

have VUR. Anorectal anomalies are also common. müllerian duct anomalies – such as uterine

duplication or vaginal septum – occur in 25% to 50% of females with unilateral renal agenesis, and

likewise, up to one-third of females with müllerian duct anomalies will have unilateral renal agenesis. It

is important to note that true agenesis is relatively rare and should not be confused with a regressed

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dysplastic kidney, which is a common fate of a multicystic dysplastic kidney (MCDK).

2 Cystic Conditions of the Kidney

Renal cystic conditions are among the most common causes of pediatric abdominal masses, especially in

infants.2 It is important to accurately diagnose them due to their different prognosis and other

associated conditions (Table 104-1).

MCDK is the most common form of nonheritable renal cystic condition.3 Prior to prenatal sonographic

screening, it used to be the most common cause of an infantile palpable abdominal mass and was often

confused with the UPJO. MCDK is a developmental anomaly resulting in multiple noncommunicating

cysts of varying sizes and is without identifiable renal parenchyma. There is typically an associated

atresia of the ureter. The classic ultrasound findings are: absence of a large central lucency (that could

be confused with renal pelvis), variably sized noncommunicating cysts, and absence of renal

parenchyma. MCDK is nonfunctional, and nuclear scintigraphy shows no activity. Majority of MCDK

will involute and regress with time to the point that they may become undetectable on conventional

ultrasound. For patients with a very large MCDK, they may not complete involution and a small

residual clump of cysts may persist into adulthood. There is a high incidence (15% to 25%) of

contralateral VUR. Several long-term registries have shown that patients with MCDK do well, and

previous concerns of hypertension, infection, malignancy, and pain are thought to be very rare. Surgery

is rarely necessary unless there is confusion about the diagnosis with a cystic Wilms tumor or failure to

regress with worrisome changes on serial imaging. Rarely, it will cause any symptoms.

Table 104-1 Classification of Congenital Renal Cystic Diseases

Autosomal recessive polycystic kidney disease (ARPCKD) – also known as infantile polycystic kidney

disease – results from mutations in the PKHD1 gene of the chromosomal locus 6p12.2. The classic

presentation is a child born with bilateral large palpable kidneys that appear very bright on ultrasound.

The hyperechogenic appearance is due to the multiple cystic surfaces reflecting the sonographic waves.

Kidney function is uniformly poor, and oligohydramnios with pulmonary hypoplasia occurs in up to

50%. Among those who survive infancy, 30% progress to end-stage renal failure. Long-term survivors

can also develop portal hypertension, esophageal varices, and hypersplenism due to concomitant

periportal fibrosis. There is no specific therapy other than kidney transplantation.

Autosomal dominant polycystic kidney disease (ADPCKD) – adult-onset type – primarily affects the

kidneys but also can have significant effects on the pancreas, liver, brain, and blood vessels. The usual

onset is postpubertal with most patients progressing to renal failure by the fourth to sixth decade of life,

depending on the severity of penetrance. Two gene mutations are associated: PKD1 (85%) and PKD2

(15%) on chromosome 16. These genes encode membrane proteins that affect cilium and calcium

signaling. Cysts are present in the pancreas and liver, as well as cerebral berry aneurysms in the circle

of Willis. Autopsies of patients with ADPCKD found that 22% have cerebral aneurysms, and about 10%

of adult patients with ADPCKD die of subarachnoid hemorrhage. Though primarily a condition of

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adolescents and adults, pediatric care providers should be aware of ADPCKD due to the nature of its

inheritance. It affects 1 in every 400 to 1,000 people.

Acquired renal cystic disease of renal failure (ARCD) is a term that refers to the development of renal

cysts in patients with end-stage renal failure. Regardless of the type of therapy (peritoneal or

hemodialysis), cysts can develop in the kidneys. The longer the period of time of dialysis the more

prevalent the cysts become. By 10 years of dialysis, 90% will have cysts. Transplantation and the

restoration of normal renal function lead to cessation and regression of the cysts. The cysts are notable

because they can bleed and develop infections. More worrisome is the development of renal cell

carcinoma in about 0.2% of patients with ARCD. The condition occurs in equal frequency in adults and

children.

There are other conditions that are associated with renal cysts. Tuberous sclerosis is an autosomal

dominant condition characterized by mental retardation, epilepsy, sebaceous acne, and renal mass. The

renal tumors are benign hamartomas (usually angiomyolipomas), but cysts are also common. Von

Hippel–Lindau syndrome is an autosomal dominant condition with cerebellar hemangioblastoma, retinal

angiomata, pheochromocytoma, renal cell carcinoma (30% to 40% of all VHL patients), and cysts of the

pancreas and kidney.

Solitary Kidney

Patients with a solitary functional kidney in most cases can be expected to live a nearly normal life with

few limitations.4 Solitary kidney can be due to surgical removal for disease, congenital malformation,

trauma, regression of an MCDK, renal donation, or in rare cases, true agenesis. In general there are no

limitations on sports or other activities. Participation in contact sports (such as football, rugby, and ice

hockey) is allowed with the understanding that the participant use all of the needed protective gear and

that the risk of injury leading to organ loss is very small but not zero. For example, in American tackle

football, the risk of having cardiac arrest due to a blow to the chest, heat stroke during training, or

suffering a catastrophic central nervous system injury is actually much higher than the risk of losing a

kidney. For this reason the official position of the American Academy of Pediatrics is to allow

participation in general. It is advisable that patients know their history and be able to identify the side

of their functional kidney. It is also important to be aware that not every protective gear is subject to

standardized testing and evaluation. Helmets used in American football, soccer shin guards, and eye

protections are regulated, but most abdominal paddings are not. Therefore, although it would seem that

protection should be helpful, use of such gear should not give a false sense of security.

3, 4 ANOMALIES OF THE URETER

Ureteropelvic Junction Obstruction (UPJO)

UPJO is the most common form of congenital ureteral obstruction and is also the most common cause of

prenatally detected hydronephrosis.5 Multiple factors lead to poor transit of fluid across the obstructed

UPJ. There can be an intrinsic adynamic portion wherein the muscles lining the UPJ are aberrant. The

muscle fibers are deficient and replaced with collagen. The net effect is to alter the normal propagation

of the peristaltic waves. In addition to these intrinsic issues, there can be extrinsic factors such as

fibrous bands or aberrant lower-pole crossing vessels trapping the ureter at the UPJ.

The classic symptoms of UPJO are flank/abdominal pain, hematuria, and infection. Inexplicable

vomiting may be mistakenly termed idiopathic. Today many UPJO cases are diagnosed antenatally due

to abnormal prenatal ultrasound (Figs. 104-1 and 104-2). Ultrasound findings of dilated renal pelvis and

calyces without ureteral dilation are indicative of UPJO, but it cannot definitely establish the presence

of a true surgical obstruction. Functional study, such as diuretic nuclear renography, is commonly

required to assess both relative renal function and severity of obstruction. Magnetic resonance

urography is a newer modality, which is increasingly utilized because it avoids ionizing radiation and

yields excellent functional and anatomic details. Not all antenatally discovered UPJO need immediate

surgery, and many could be safely observed with spontaneous resolution in some, especially those with

a preserved relative renal function.

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Figure 104-1. Ultrasound demonstrating dilated renal pelvis and calyces caused by ureteropelvic junction obstruction.

UPJO repair can be done effectively using an open or laparoscopic approach, with possible aid of a

surgical robot. The principle is to excise the narrowed, dysplastic portion and reconnect the ureter and

renal pelvis back together to create a dependent drainage (Fig. 104-3). This dismembered pyeloplasty

can be done with a better than 95% success rate. Other approaches using pelvic flap are applied

selectively based on the anatomy.

Ureteral Duplication

Ureteral duplication is a common anomaly of the urinary tract. The incomplete duplication has two

ureters exiting the kidney, but they join prior to entering the bladder, so there is only one ureteral

orifice in the bladder. A complete duplication has two ureters that enter the bladder separately,

resulting in two orifices. These occur in about 1 in every 150 to 500 individuals. In a complete

duplication, the upper pole ureter ends up with a more inferior and medial orifice closer to the bladder

neck while the lower pole ureter has a superior and lateral orifice (Weigert–Meyer rule). The more

lateral position of the lower pole ureter can result in potentially shorter submucosal tunnel, making it

more prone to VUR. The more medial upper pole ureter, on the other hand, can enter ectopically into

the bladder neck and proximal urethra, resulting in obstruction. In females, the ectopic upper pole

ureter can drain to the vestigial Gartner duct (wolffian duct remnant) and thereby open up onto the

anterior lateral vaginal wall, resulting in continuous incontinence. In males, the ectopic upper-pole

ureter can insert into reproductive structures such as vas deferens and seminal vesicle, resulting in

obstruction or recurrent epididiymitis. Most patients with partial or complete duplication are otherwise

healthy.

Figure 104-2. Prenatal sonography showing dilated left renal pelvis with thin parenchyma caused by ureteropelvic junction

obstruction.

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Figure 104-3. Dismembered pyeloplasty where the obstructive segment has been excised and the anastomosis is performed

between the pelvic opening and spatulated ureter, creating a dependent drainage.

Ectopic Ureter

Ectopic ureter usually drains more caudal and inferior to the normal trigone. It is commonly associated

with a complete duplication. In males, they can exit into the prostatic urethra, bladder neck, and

epididymis (rare). In females, they can drain into the bladder neck, urethra, and vagina. For girls, an

ectopic ureter that drains outside of the bladder is the classic cause of persistent day and night wetting

despite otherwise excellent toilet habits. This can be a vexing condition for many patients and families,

but once properly diagnosed, it offers one of the most successful surgical solutions for incontinence (Fig.

104-4). Treatment is usually upper pole partial nephrectomy or reimplant of the upper pole ectopic

ureter into the bladder.

Ureterocele

Ureterocele develops as the result of a narrowed opening of the ureteral orifice.6 The narrow opening

results in submucosal and ureteral dilation that can extend all the way up to the kidney. The dilation

varies in severity. It can be mild, contained wholly within the bladder wall and appear like a pearl

onion (Fig. 104-5). Or it can be massive and create a cavernous space under the trigone, extending

beyond the bladder neck and into the urethra (Fig. 104-6). Ureteroceles are typically associated with

upper pole ureter of a complete duplication. Single-system ureteroceles do occur but are rare. Similar to

UPJO, they are often found as part of an antenatal hydronephrosis evaluation. Other common

presentation is symptomatic urinary tract infection (UTI) or prolapse. Infected ureterocele can cause

severe sepsis and requires an emergent decompression of the ureterocele using an endoscopic

transurethral puncture. Options for longer term, more definitive treatment approaches are designed

depending on the salvageable function of the upper moiety. If the upper pole is functional, it is usually

preserved, and the surgical approach is aimed at eliminating the distal ureteral obstruction at the

ureterocele. The dilated ureter is tapered and reimplanted into the bladder after excising the

ureterocele, either separately or en bloc with the normal lower-pole ureter in a common sheath.

Alternatively, the upper pole ureter can be connected to the lower-pole pelvis (ureteropyelostomy) near

the kidney. If the upper pole is nonfunctional, a partial nephrectomy is preferred. Advances in

minimally invasive surgery make laparoscopic and robotic techniques practical in even small children.

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Figure 104-4. Ectopic ureter opening outside the bladder and urethra causing continuous incontinence. Catheter is inserted into the

left upper pole ectopic ureter.

Figure 104-5. Intravenous urogram demonstrating ureterocele that has an appearance of “Pearl onion.”

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Figure 104-6. Bulging right ureterocele belonging to the upper pole. Bladder has been opened. Catheters are inserted into the right

lower pole ureter and left ureter.

Megaureter

A persistently dilated ureter from the kidney all the way to the ureterovesical junction (UVJ) is referred

to as megaureter.7 They are classified by description and causation. They can be refluxing, obstructing,

refluxing/obstructing, and nonobstructing/nonrefluxing. When they are due to an intrinsic abnormality

of the distal ureter (such as fibrosis of the UVJ), it is a called primary megaureter. When it is caused by

another condition of the bladder (such as a neurogenic bladder or bladder outlet obstruction), it is called

a secondary megaureter. Primary megaureters, like UPJO and ureterocele, are often diagnosed

prenatally. Majority of moderate megaureters – especially those detected in utero – improve with

observation. If they require treatment because of pain, UTI, or poor renal function, they can be

temporarily drained with a stent, nephrostomy, or cutaneous ureterostomy. Long-term solution requires

a ureteral reimplantation with tapering of the wide ureter.

5 Vesicoureteral Reflux

The ureter transports urine from the pelvis to the bladder with active antegrade peristalsis. Once in the

bladder, the urine is stored until it is emptied without sending the urine back toward the kidney. This

whole process is independent of gravity. When the bladder urine moves in a retrograde manner toward

the kidney, it is termed as VUR (Fig. 104-7).8 It is an abnormality that can occur primarily due to a

congenital deficiency in the UVJ submucosal tunnel or secondarily to high bladder pressures such as in

patients with neurogenic bladder or posterior urethral valves (PUVs). The incidence of VUR in general

population is estimated to be around 1%. The incidence is much higher in children who present with

UTI and hydronephrosis. Among children age 4 years or less who present with a first-time UTI, the VUR

incidence can be as high as 40%. VUR is found in 25% to 30% of children with antenatal

hydronephrosis. The primary form of VUR occurs because the length of the intramural tunnel – so-called

flap valve (like stepping on a straw on the ground) – is insufficient to seal the ureter during bladder

filling and emptying. The secondary form usually occurs because of high storage pressure that

overwhelms an otherwise normal intramuscular tunnel. Reflux is of clinical significance because it

interferes with effective emptying of urine and helps bacteria ascend to the kidneys more easily,

thereby transforming cystitis into potentially damaging renal parenchymal infection (pyelonephritis).

Pyelonephritis in turn increases the risk of long-term kidney damage by creating parenchymal scar.

Infants and children are more prone to scarring than adults. Renal scarring and damage early in life can

increase the risk of hypertension and pregnancy-related complications in females.

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