Polycystic Kidney Disease

Can be autosomal dominant, recessive, or sporadic (sporadic is very rare). Characterized by multiple, bilateral fluid-filed cysts caused by defects in the primary cilia of the renal tubule cells. See Gross Image The exact role of the primary cilia in renal cyst formation is uncertain, but it's thought to play a key role in the signaling pathways that establish and maintain functional tubule epithelium differentiation. Cysts arise from the tubule epithelial cells: the dysregulated tubules dilate and fill with filtrate, and eventually separate to form cysts. As they grow and multiply, the cysts enlarge the kidneys and impair renal functioning by displacing normal parenchyma and compressing the vasculature, which can lead to renal failure. Caused by mutations in the genes PKD1 or PKD2, which code for the polycystin proteins. This disorder has complete penetrance; clinical manifestations are present in many patients by age 30, and are present in all patients by age 80. Because patients don't typically experience signs or symptoms of autosomal dominant polycystic kidney disease until adulthood, we used to call this form of polycystic disease "adult polycystic disease." The most common direct signs and symptoms include:

• Flank and abdominal pain with proteinuria and hematuria
• Hepatic cysts
• Renal stones and urinary tract infections
• Hypertension (due to activation of the renin-angiotensin-aldosterone system), cardiovascular problems, and intracranial aneurysms.

Treatments: There is no cure for autosomal dominant polycystic kidney disease, but we can give Tolvaptan to slow the growth of kidney cysts and antihypertensive drugs (ACE inhibitors and ARBs) to help manage the disorder. Caused by mutations in PKHD1 (which codes for fibrocystin, aka, polyductin) and DZIP1L (which has a role in cilia formation). Rarer and more severe than the autosomal dominant form, and, because it often leads to renal failure in early childhood, was formerly called "pediatric" or "infantile" polycystic kidney disease. The cysts tend to be in the collecting tubules and create a dilating radial pattern. See Gross Image In addition to polycystic kidneys, children with autosomal recessive polycystic kidney disease also tend to have hepatic fibrosis and hypertension; fetuses with severe renal impairment may have pulmonary hypoplasia, which is often fatal. Due to early and severe renal impairment, patients require hemodialysis and kidney transplants.