Recognition and Management of a Less Common Cause of Chronic Kidney Disease: Autosomal Dominant Polycystic Kidney Disease

LEARNING OBJECTIVES
After reading this review article on ADPKD, participants should be able to:
• Identify people at high risk for ADPKD
• Conduct a diagnostic evaluation
• Initiate evidence-based therapy to slow kidney progression and treat
extra-renal manifestations

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder with an incidence of 1 in 1000 live births in the United States. The progressive development and enlargement of renal cysts results in an exponential increase in total kidney volume.
Some polycystic kidneys grow to be as large as a football and weigh as much as 30 pounds. Despite destruction of renal parenchyma, normal renal function usually is maintained for decades because of compensatory hyperfiltration in surviving glomeruli. However, when the majority of nephrons have been destroyed, typically during the fourth decade of life, renal function begins to decline, often leading to end-stage kidney disease (ESKD).
This is in sharp contrast to the much rarer autosomal recessive form of polycystic kidney disease that often is apparent at birth or in early infancy, frequently leading to death early in life. ADPKD is caused by mutations in the PKD1 and PKD2 genes. These genes provide instructions for making proteins thought to be involved in normal kidney development, organization, and function. Approximately 90% of individuals with ADPKD inherit a PKD1 or PKD2 mutation from 1
affected parent. The other 10% of cases are acquired, resulting from a new mutation in 1 of the genes in people with no family history of the disorder.
Historic evidence indicates that the PKD1 mutation occurs in 85% of people with ADPKD and the PKD2 mutation in 15%. Recent evidence in individuals from Canada and the United States suggests that the revalence of PKD2 could be approximately 30%. Variants in other genes linked to PKD, as well as environmental factors such as acute kidney injury, can influence cyst formation and disease progression. Compared with PKD2, PKD1 mutation is associated with greater cyst number and
volume at a given age and results in more severe disease.
People with the PKD2 genetic mutation generally experience milder kidney disease with fewer kidney cysts, delayed onset of hypertension and ESKD by nearly 2 decades, and longer overall survival. However, because the renal prognosis differs according to the type of mutation in both PKD1 and PKD2, the renal prognosis of patients with a PKD2 mutation is not always favorable compared with patients with a PKD1
mutation.

Post presentation survey link: https://wh1.snapsurveys.com/s.asp?k=159234582163