Developmental Abnormalities of the Genitourinary System

Renal Agenesis

Renal agenesis is the congenital absence of the kidneys. Renal agenesis can be bilateral or unilateral. Bilateral renal agenesis occurs in roughly 1 in 4000 births, with male predominance. Prenatally, it is discovered in the second or third trimester because of severe oligohydramnios on ultrasound. Findings of absent kidneys, no bladder filling, and lack of renal arteries on color Doppler ultrasonography support the diagnosis. Postnatally, infants are noted to have the characteristic Potter facies with a prominent skin fold from the eye to the cheek, blunted nose, low-set ears, and orthopedic abnormalities, including clubbed legs or fused lower extremities. Lack of adequate amniotic fluid results in pulmonary hypoplasia and respiratory distress. These findings, or lack of urine output within 24 hours, should prompt renal ultrasound. Bilateral renal agenesis is almost universally fatal, with 40% demise in utero due to cord compression, and those born alive surviving for less than 48 hours because of pulmonary compromise. There have been reports of survival of monoamniotic twins discordant for bilateral renal agenesis and reports of bilateral renal agenesis managed with serial amnioinfusion with survival through delivery with successful initiation of peritoneal dialysis, but in general prognosis remains poor. There is an increased prevalence of congenital renal anomalies in relatives, and screening ultrasound has been recommended for parents and siblings of children with renal agenesis.

Unilateral renal agenesis occurs in approximately 1 in 500 to 1000 births. The true incidence can be difficult to measure because of the frequent involution of multicystic dysplastic kidneys. In fetal ultrasounds with a unilateral empty renal fossa, 47% have an absent kidney, while most of the rest have renal ectopia. Unilateral renal agenesis is associated with abnormalities of the paramesonephric and mesonephric ducts, including absence of the ipsilateral uterine horn or vas deferens. Due to the risk of obstruction at the time of menarche, screening for OHVIRA syndrome (obstructed hemivagina with ipsilateral renal agenesis) at puberty should be considered. About a third of children with unilateral renal agenesis will have extra-renal anomalies including gastrointestinal, cardiac, and musculoskeletal; there is also an association with a number of multisystem syndromes. There is an increased risk of contralateral renal anomaly, including UPJO and VUR.

Patients with unilateral renal agenesis have a higher risk of end stage renal disease than those with solitary kidney from donor nephrectomy or MCDKD, with 50% requiring dialysis by 30 years of age. Because of the low risk of renal injury, the American Academy of Pediatrics recommends participation in sports for those with solitary kidney, particularly non-contact sports. Children with unilateral renal agenesis should be followed regularly to monitor urine protein, blood pressure, and kidney function blood pressure.

Renal Ectopia and Fusion

Renal ectopia describes a kidney that fails to reach its standard location. The kidney can be pelvic, iliac, abdominal, thoracic, and contralateral or crossed. Renal ectopia occurs in about 1 in 700 infants on ultrasound screenings. Abnormalities of renal ascent during fetal development are thought to be the cause of ectopia. Most patients with renal ectopia are asymptomatic.

Half of ectopic kidneys are hydronephrotic, of which 50% are due to obstruction, 25% are due to vesicoureteral reflux, and 25% are due to abnormal rotation without obstruction. There is a strong association with extrarenal anomalies, which are seen in almost half of patients. An association with genital anomalies is common, and a large number of girls with müllerian anomalies, including cloacal anomalies, are also noted to have ectopic kidneys. Because of this, the finding of an ectopic kidney in a female should prompt further investigation. Prognosis for the ectopic kidney is good, with no evidence of adverse effects on blood pressure or renal function.

When the ectopic kidney is located on the opposite side from where its ureter enters the bladder, this is called crossed renal ectopia . This is found in 7.5 per 10,000 newborns, and 90% of these kidneys are also fused to the adjacent kidney. The cause of crossed renal ectopia is unknown. The condition is found more commonly in males, and left-to-right crossover is most frequent. Approximately 20% to 40% of patients with crossed renal ectopia also have VUR, and there is a high incidence of associated cardiac, skeletal, genital anomalies with solitary crossed renal ectopia, although it is not known if this is due to the ectopia or the agenesis.

The most common renal fusion abnormality is the horseshoe kidney, which consists of two renal masses on either side of the midline connected by an isthmus of tissue. Horseshoe kidney is found in approximately 1 in 600 on autopsy study. There is male predominance, an association with syndromes such as Edwards syndrome, Down syndrome, and Turner syndrome, and an increase in associated genitourinary anomalies, including hypospadias, undescended testes, bicornuate uterus, septate vagina, and duplication of the ureter. Up to half of children with horseshoe kidney have associated urologic anomalies including VUR and UPJO.

Most patients with horseshoe kidney are asymptomatic, although the incidence of Wilms tumor is higher in patients with horseshoe kidney than in the average population, and about a third develop stones in adulthood. Neither risk is significant enough to justify routine screening of these patients.

Supernumerary Kidney

A supernumerary kidney is a separate or loosely attached renal mass with its own blood supply and collecting system. It is exceedingly rare, with only about 100 cases reported. About 50% have a structural abnormality such as a duplicated system or hydronephrosis, and this condition is usually diagnosed due to infection, obstruction, or urinary incontinence.

Cystic Disease of the Kidney

Cystic diseases of the kidney are classified as having inheritable or noninheritable causes ( Box 76.2 ). Most cases present during the neonatal period.

Multicystic Dysplastic Kidney

Multicystic dysplastic kidney disease is the most common type of renal cystic disease, occurring in 1 in 4300 live births. It is diagnosed based on ultrasound findings of a collection of cysts of various sizes without any evidence of renal parenchyma ( Fig. 76.2 ). There is a male and a left-sided predominance. The cause is unknown. Since 60% of MCDK will involute spontaneously with associated contralateral hypertrophy, early nephrectomy is rarely needed. While vesicoureteral reflux is common in the contralateral kidney, it is rarely clinically significant and so a screening voiding cystourethrogram (VCUG) should be considered only if there are anomalies on the contralateral kidney. Poor neonatal outcomes are generally only found when there are contralateral or extrarenal anomalies. Isolated multicystic dysplastic kidneys typically follow a benign course with hypertension and malignancy occurring at a similar proportion to general population.

Renal Tumor

Malignancies are rare in neonates, and renal tumors make up 7% to 12% of neonatal malignancies. The most common finding of renal tumor is a palpable abdominal mass, but more commonly they are noted on prenatal ultrasound, after which a fetal MRI can help characterize the lesion. The first line of treatment is radical nephrectomy for all unilateral renal tumors. Biopsy before surgery is generally reserved for complex cases such as those with bilateral disease or metastases at presentation.

The most common renal tumor in neonates is congenital mesoblastic nephroma, generally diagnosed before 3 months of age. There is a male predominance of 1.5:1. The mainstay of treatment is a radical nephrectomy, and surgery is generally curative in stage I/II tumors, with rare need for chemotherapy. The overall survival rate for congenital mesoblastic nephroma is excellent, around 95%.

Wilms tumor is the second most common neonatal renal tumor. It affects males and females equally and is associated with several syndromes, including Beckwith-Wiedemann syndrome, WAGR syndrome, Denys-Drash syndrome, and Perlman syndrome. Treatment generally begins with radical nephrectomy, although there is increasing evidence that partial nephrectomy in appropriately selected patients is safe and may be preferred for those with bilateral masses or predisposing syndromes. After surgery, treatment is based on risk stratification and may include chemotherapy and radiation therapy based on protocols from two international oncologic groups, the Children’s Oncology Group and the International Society of Pediatric Oncology. The overall survival rate is high at 90%, but long-term survivors are at risk of cardiac disease, adverse pregnancy outcomes, and renal dysfunction, as well as secondary primary tumors in 16%.

Malignant rhabdoid tumor of the kidney is a rare and aggressive cancer that generally presents at advanced stages. The overall survival rate in neonates is 16%. Other renal tumors in neonates include clear cell carcinoma of the kidney, which presents at advanced stage but for which there is an overall survival rate of 50%, ossifying renal tumor of infancy, which is generally benign, nephroblastomatosis, which is a premalignant condition requiring observation, and cystic nephroma, which is benign but indistinguishable from rare malignancies and therefore generally surgically removed.

Renal Vein Thrombosis

The risk factors for renal vein thrombosis include umbilical vein catheterization, perinatal asphyxia, maternal diabetes, and dehydration, as well as the presence of prothrombotic states. The classic presentation is gross hematuria, a palpable flank mass, and thrombocytopenia. Contrast angiography is the gold standard for diagnosis, but because of concerns regarding radiation, Doppler ultrasound is often used as an alternative. This will show enlarged and echogenic kidneys with either absent flow in the renal vein or increased resistance in the renal artery. The current standard is treatment with anticoagulation; thrombolysis can be considered with life-threatening renal vein thrombosis. Optimal targets for anticoagulation have not been established, so adult ranges are generally used. Even with anticoagulation, over 60% of affected kidneys will become atrophic.

Adrenal Hemorrhage

Adrenal hemorrhage occurs after birth in approximately 2 in 1000 live births. While presentation can include prolonged jaundice, palpable abdominal mass, anemia, or scrotal hematoma, these symptomatic cases are less common in the era of ultrasound diagnosis. Predisposing factors include vaginal birth, macrosomia, perinatal hypoxia, birth asphyxia, and sepsis. Treatment is generally supportive and adrenal insufficiency rare. Serial ultrasounds should be obtained to confirm resolution given the rare chance of a fetal neuroblastoma mimicking an adrenal hemorrhage.

Duplication of the Ureters

Ureteral duplication can develop if there are duplicate ureteral buds or early division of these buds. Ureteral duplication occurs in between 0.8% and 1.67% of the population. Ureteral triplication and even quadruple ureters have also been reported in the literature, but are much rarer. Complete duplication results in two separate ureters, while partial duplication results in a bifid renal pelvis with distal confluence into a single ureter. There is a strong genetic link to duplication of the ureter, which occurs in 12% of screened siblings and parents of affected patients. Diagnosis is generally by ultrasound. Some clues can indicate a duplex kidney prenatally, including renal length greater than the 95th percentile with a cyst-like structure in the upper pole surrounded by a rim of parenchyma, two noncommunicating renal pelvises, or a cystic structure in the bladder consistent with a ureterocele. The location of the ureters in the bladder of patients with complete ureteral duplication generally follows the Weigert-Meyer law, with the upper pole ureter found caudal to the lower pole ureter.

About half of patients with duplex kidneys are otherwise asymptomatic, and the anomaly by itself is not thought to have any clinical significance. Duplex kidneys is, however, associated with other conditions; a quarter of patients have upper pole obstruction, usually associated with a ureterocele, 10% have lower pole scarring, and 4% have lower pole VUR. Both lower pole UPJO and rarely upper pole UPJO have been reported, as has upper pole ectopia. Long-term renal outcome is generally related to the presence of these associated conditions, although ureteral duplication itself is a risk factor for a slower rate of spontaneous reflux resolution.