Brief Introduction and Genetics of Autosomal Dominant Polycystic Kidney Disease (ADPKD)

ADPKD is the most common life-threatening monogenic disease. It occurs worldwide and in all races, affecting 1 in 400–1000 individuals. In the United States, approximately 500,000 people are affected and about 2000 begin hemodialysis each year.

ADPKD is an autosomal dominantly transmitted disease. It is composed of two types: ADPKD1, caused by mutations in the PKD1 gene and responsible for 85% of the clinical cases of ADPKD, and ADPKD2, caused by mutations in the PKD2 gene and accounting for approximately 15% of cases. A very small percentage of ADPKD patients, with a milder form of disease not linked to mutations in either PKD1 or PKD2, might have mutation(s) in a yet to be identified third PKD gene.

The severity of cystic renal dysfunctions is highly heterogeneous with significant interfamilial and intrafamilial variations. In general, ADPKD1 is more severe and is marked by an early onset of end-stage renal failure (mean age of 54 years) versus that of ADPKD2 (mean age of 74 years). Compared to female patients male ADPKD2 patients tend to develop more extensive cystic renal dysfunction, although they have less cystic liver disease.