66 Congenital Anomalies of the Kidney and Urologic System

This chapter reviews several common congenital and inherited anomalies of the kidney and urologic system. Congenital abnormalities are a frequent cause of renal failure in children, accounting for more than 30% of end-stage renal disease (ESRD). Congenital anomalies can be subdivided into three categories based on the stage of the primary abnormality in renal embryologic development (Figure 66-1). The first category refers to a failure to form a functional nephron, leading to renal parenchyma malformations, such as renal agenesis or cystic dysplasia. The second group of defects relates to a failure of the developing kidney to migrate to its appropriate destination. This may lead to renal ectopy (pelvic or thoracic kidneys) or fusion abnormalities, such as a horseshoe kidney. The third category describes defects of the urinary collecting system, such as double ureters or posterior urethral valves (PUVs). Here, changes of the renal parenchyma (hydronephrosis, dysplasia) are often secondary to obstructive uropathy or urinary reflux disease. Inherited conditions such as the polycystic kidney diseases (PKD) are the result of specific genetic mutations that may present with detectable renal abnormalities at birth or may not develop until later in life. The following sections detail common and exemplary conditions representative of these subcategories.

Figure 66-1 Congenital anomalies categories.

Polycystic Kidney Disease

PKDs are a group of genetically inherited conditions in which cyst formation and renal parenchymal replacement can occur at anytime from fetal life to adulthood. There are two major forms, autosomal dominant PKD (ADPKD) and autosomal recessive PKD (ARPKD) (Table 66-1). In addition, a number of rare pleiotropic disorders exist, which are loosely associated because of similar clinical and pathophysiologic features, including renal cystic and hepatobiliary disease (Table 66-2). All of these disorders share ciliary dysfunction as a common principle in their pathogenesis. PKD proteins have been localized to the cilia or basal body, and loss or abnormalities of cilia in the kidney are associated with cyst development (Figure 66-2).

Table 66-1 Autosomal Recessive Polycystic Kidney Disease versus Autosomal Dominant Polycystic Kidney Disease

	Autosomal Recessive Polycystic Kidney Disease	Autosomal Dominant Polycystic Kidney Disease
Gene	Chromosome 6p21.2-p12	Chromosome 16p13.3, chromosome 4q13-q23
Protein	Fibrocystin	Polycystin 1, polycystin 2
Age of presentation	Commonly prenatally, childhood, adolescence	Highly variable
Renal cysts	Radial pattern	Anywhere in kidney, varying size
Extrarenal manifestations	Biliary obstruction, hepatic fibrosis with portal hypertension, liver failure	Liver cysts, pancreas cysts, vascular cysts (“Berry aneurysms”)
Things in common	Renal cysts do not communicate. Disease may present at any age, including prenatally. Gene defect leads to malfunction of the ciliary body. The kidneys are usually enlarged. Usually bilateral disease (exception: early diagnosis ADPKD in childhood with positive family history)

Table 66-2 Overview of the Ciliopathies*

Figure 66-2 Renal cystic diseases.

Autosomal Recessive Polycystic Kidney Disease

ARPKD typically presents early in life and is commonly detected in utero by routine prenatal ultrasound. Severe cases may be associated with the Potter sequence (i.e., oligohydramnios with subsequent lung hypoplasia and characteristic limb and facial abnormalities resulting from decreased intraamniotic space). ARPKD is reported to have an incidence of one in 20,000. The phenotype can be quite variable. One-third of identified patients do not survive beyond the neonatal period mainly because of respiratory insufficiency. Of those who survive infancy, approximately one-third will need chronic renal replacement therapy. In addition to the renal manifestations, cystic biliary dysgenesis is another hallmark of ARPKD. It can result in congenital hepatic fibrosis and may present later in childhood or adolescence, even in adults. Characteristically, patients presenting later in life have less severe renal disease and more prominent hepatic fibrosis. Hepatic fibrosis may lead to portal hypertension, gastrointestinal bleedings from esophageal varices, cholangitis, and hepatic failure. The gene identified with ARPKD is on the short arm of chromosome 6 and encodes fibrocystin (polyductin). Fibrocystin is expressed on the cilia of renal and bile duct epithelial cells and is thought to be critical in the maintenance of normal tubular architecture in the renal and biliary systems.

The diagnosis is established based on classical radiographic features. The classic sonographic appearances in newborns are large kidneys, increased echogenicity of the parenchyma, and loss of corticomedullary differentiation. There may be macrocysts that are less than 2 cm in diameter. The cysts are subcapsular extensions of radially oriented ectatic spaces. In addition to the sonographic findings, the diagnosis of ARPKD requires one or more of the following: (1) absence of renal cysts in both parents, (2) a previously affected sibling, (3) consanguinity, or (4) hepatic fibrosis.

Treatment is largely supportive. The primary prognostic determinant in the newborn period is the degree of lung hypoplasia. Renal failure and portal hypertension are treated with medications, dialysis, or transplant depending on an individual patient’s symptoms. In childhood, the most common features are renal failure, electrolyte abnormalities, and hypertension. The hypertension is usually responsive to angiotensin-converting enzyme inhibitors. Hepatic fibrosis may cause portal hypertension with resulting esophageal varices, gastrointestinal bleedings, and hypersplenism with thrombocytopenia. Liver failure may in some cases require liver transplant. Cholelithiasis is common. Ascending cholangitis is a potentially life-threatening concern.

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