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 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.
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.
, 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.
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 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.
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 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 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.
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.”
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.
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.
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.
Figure 104-7. Vesicoureteral reflux to the left lower pole ureter.
VUR severity is described using the International Reflux Study scale. Grading is important for several reasons. Most VUR patients (80%) have grades I or II with an excellent chance of spontaneous resolution (75% to 90%) over time. The higher grades (III to V) are less likely to improve with time and more often require surgery. The diagnosis of VUR depends on the demonstration of reflux on an imaging study. Voiding cystourethrogram (VCUG) is the preferred imaging modality. It offers excellent anatomical detail of the entire lower urinary tract (bladder and urethra) and reproducible grading. In males, it provides important details regarding urethra such as possible valves. The presence of other anomalies such as periureteral diverticulum can affect the clinical decision-making. Alternatively one can use nuclear cystogram (NUC) that offers less anatomical detail and a different grading system (grades 1 to 3) but is offset by the advantage of less radioactive exposure and the ability to continuously monitor reflux throughout filling and emptying. Ultrasound of the kidneys and bladder, while helpful in assessing renal size and appearance, cannot diagnose reflux. The detection of kidney scarring is usually confirmed with nuclear renal scintigraphy using DMSA (Fig. 104-8).
Figure 104-8. DMSA renal scintigraphy demonstrating renal parenchymal defect associated with pyelonephritis. A: Cortical defects seen in the right kidney during the acute phase of pyelonephritis. B: The same kidney 6 months later showing a persistent cortical scar involving the upper pole.
The management of children with VUR depends on their presentation and other clinical factors (Fig. 104-9). The vast majority of patients have low-grade VUR and are expected to resolve spontaneously with time. They can be managed with low-dose antibiotic prophylaxis with intermittent testing every 1 to 2 years. The most recent multi-institution randomized clinical trial suggested that antibiotic prophylaxis is beneficial in children with dilating, high-grade reflux (grade III or higher). If they cannot remain infection free and sustain breakthrough infections, surgery may be necessary to prevent recurrent renal parenchymal infection. For most patients, spontaneous resolution occurs after 4 to 5 years and those who fail to resolve may also need surgery. There are two major surgical options. There is the less invasive endoscopic approach. Using cystoscope, a small bleb of a bulking material is injected into the floor of the ureteral orifice. This creates a submucosal mound that turns the usual round oval opening into an upside-down crescent. Currently, FDA-approved dextranomer/hyaluronic acid copolymer (Deflux®) is available for this approach. The efficacy of Deflux® injection is good but not spectacular. About 70% to 75% of VUR can be corrected with this approach. Lower the grade, the more likely that injection will succeed. The long-term durability also remains unknown. The more time-tested surgery for correcting VUR is ureteral reimplantation (ureteroneocystostomy), where the ureter is revised or repositioned to create a more effective ureterovesical flap-valve mechanism by restoring the submucosal tunnel. The affected ureter is detached and mobilized. A new submucosal tunnel of sufficient length (more than 4 to 5 times the width of the ureter) is created, and the ureter is placed into it. It is critical that the muscle underneath the tunnel is firm and secure to allow the collapse of the reimplanted ureter with bladder filling and emptying. The ureter may require tapering (in megaureter or obstructed upper pole of duplication anomaly), so it can meet the needed width-to-length ratio of the tunnel. An extravesical approach is called detrusorraphy, where the muscle flaps are freed from the underlying bladder mucosa and wrapped behind the ureter at the UVJ to create a more effective flap-valve mechanism. The success rate of open surgery for VUR is very high (96% or more for grades III or less).
Traditionally, all children who present with a culture-proven UTI were recommended to undergo evaluation for VUR using ultrasound and VCUG. More recently this paradigm has been called into question because of the observation that some children seem to tolerate VUR better than others without long-term clinical problems, especially those with low-grade VUR. A modified evaluation approach using the initial ultrasound has been suggested. Because the key concern with VUR is the prevention of kidney damage and its consequences (hypertension, scarring, and loss of renal function), some argued that because most VUR are of low grade and most cases of low-grade VUR resolve spontaneously, it may be reasonable to defer VCUG for only those patients who have recurrent UTIs or whose ultrasound is abnormal. This led to a major shift in the recommendations from the American Academy of Pediatrics (AAP) in 2011. Others have argued that determining the presence of renal scarring should be the dominant factor and advocated an initial nuclear DMSA renal scintigraphy rather than ultrasound. Recently a double-blind controlled randomized clinical trial looked into the benefits of antibiotic prophylaxis. The Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) study that completed in 2014 studied 600 children with proven VUR.9 Half received antibiotic prophylaxis and half received a placebo. Prophylaxis reduced the risk of recurrent UTI by 50%, especially in those with dilating, high-grade reflux (III to V). The occurrence of new renal scarring however did not differ significantly between the two groups.
Figure 104-9. International reflux grading system. Majority of reflux are grades I or II, with high likelihood of spontaneous resolution, whereas higher grades (III to V) with dilating ureters are at a greater risk of UTI, renal injury, and nonresolution, often requiring surgery.
Women with a history of VUR may be at increased risk later in life for UTI during pregnancy regardless of whether the VUR was corrected or not. Renal scarring rather than the presence of active VUR itself appeared to be a key risk factor for pregnancy-related morbidity. In general, for girls with VUR, the families should be aware that when they become adults of child-bearing age, they need to know their medical histories, so that appropriate perinatal care and monitoring is instituted.
During fetal development, urachus is the cephalad attachment of the cloaca to the allantois. As the bladder and urethral sphincter develop, it becomes atretic. It remains only as a fibrous cord from the dome of the bladder to the umbilicus. Occasionally the urachus remains patent either completely or partially. When completely open (patent urachus), urine can be found exiting the umbilicus. In other cases, there can be a deep sinus or entrapped cyst. These can be areas that can be infected due to poor drainage and present with fever, nausea, and umbilical drainage. Detection is usually made by clinical suspicion, along with abdominal ultrasound or other imaging. Because the epithelial lining of the urachus is that of the bladder and not of the skin, rarely tumors can occur. Mucinous adenocarcinoma is thought to arise from the urachal remnant in middle-aged or elderly patients. For this reason, when detected, even when asymptomatic, some have advocated prophylactic removal.
During development if the cloacal membrane fails to breakdown at the appropriate time, medial migration of the mesenchyme to form the anterior abdominal wall is affected. The bladder can end up as an exposed urothelial plate (bladder exstrophy) (Figure 104-10).10 The urethra may be incompletely formed dorsally (epispadias). The whole lower abdomen can be exposed with the hindgut or colon being unformed with the bladder split into two halves (cloacal exstrophy). Pelvic bone is also abnormally developed, and there is a diastasis of pubic symphysis.
The least severe manifestation is epispadias. In males, it is a defect with a dorsally placed urethral meatus and urethra, along with dorsal penile curvature. Visually it looks like a reverse, dorsal form of hypospadias. When the meatus is very proximal, the bladder neck and continence can be affected. In females, epispadias typically present with bifid clitoris (Fig. 104-11). It is more commonly associated with bladder exstrophy, but can occur as an isolated defect. Recognition and protection of the bladder plate against contact irritation is important. If possible, primary closure of the exposed bladder plate, pelvic placement and abdominal closure should be done during infancy. Most studies have suggested that a concomitant pelvic osteotomy is beneficial for successful initial closure as well as the subsequent bladder function. Repair can be staged with closure of the bladder first, followed by later bladder neck reconstruction and epispadias repair. Alternatively a complete primary repair could be accomplished with simultaneous closure of the bladder plate and reconstruction of the epispadias and genitalia. Bladder exstrophy is associated with other anomalies including inguinal hernia and VUR.
Figure 104-10. Male bladder exstrophy with associated epispadias.