Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening monogenic genetic disorder, caused by autosomal dominant mutations in the PKD1 and PKD2 genes; it is a quantitatively important cause of ESRD. Autosomal recessive polycystic disease is a less much common cause of renal failure, typically presenting in infancy; hepatic involvement is much more prominent. The massive renal cysts in ADPKD can lead to progressive CKD, episodic flank pain, hematuria (often gross), hypertension, and/or urinary tract infection. The kidneys are often palpable and occasionally of very large size. Hepatic cysts and intracranial aneurysms may also be present; pts with ADPKD and a family history of ruptured intracranial aneurysms should undergo presymptomatic screening. Other common extrarenal features include diverticulosis and mitral valve prolapse.

The expression of ADPKD is highly variable, even within individual families, with the age of onset of ESRD ranging from childhood to old age. The renal phenotype is more severe in pts with mutations in PKD1, who on average develop ESRD approximately 15 years earlier than those with PKD2 mutations. Indeed, some pts with ADPKD discover the disease incidentally in late adult life, having had mild to moderate hypertension earlier.

The diagnosis is usually made by ultrasonography. In a 15- to 29-year-old at-risk individual from a family with ADPKD, the presence of at least two renal cysts (unilateral or bilateral) is sufficient for diagnosis. Notably, however, renal cysts are a common ultrasound finding in older pts without ADPKD, particularly those with CKD. Therefore, in at-risk individuals 30–59 years of age, the presence of at least two cysts in each kidney is required for the diagnosis; this increases to four cysts in each kidney for those aged >60. Conversely, the absence of at least two cysts in each kidney excludes the diagnosis of ADPKD in at-risk individuals between the ages of 30 and 59.

Hypertension is common in ADPKD, often in the absence of an apparent reduction in glomerular filtration rate. Activation of the renin-angiotensin system appears to play a dominant role; angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are the recommended antihypertensive agents, with a target blood pressure of <130/80 mmHg. Dual therapy with an ARB and ACE inhibitor does not confer additional benefit in slowing progression of ADPKD to ESRD. Promising treatment modalities for halting progression of CKD in ADPKD include vasopressin antagonists, somatostatin analogues, and inhibitors of cell proliferation.

Urinary tract infections are also common in ADPKD. In particular, pts may develop cyst infections, often with negative urine cultures and an absence of pyuria. Pts with an infected cyst may have a discrete area of tenderness, as opposed to the more diffuse discomfort of pyelonephritis; however, clinical distinction between these two possibilities can be problematic. Many commonly used antibiotics, including penicillins and aminoglycosides, fail to penetrate cysts and are ineffective; therapy of kidney infections in ADPKD should use an antibiotic that is known to penetrate cysts (e.g., quinolones), guided initially by local antimicrobial susceptibility patterns.