Polycystic kidney disease (PKD) includes inherited diseases that cause an irreversible decline in kidney function. PKD may be inherited as an autosomal dominant or recessive trait. The autosomal dominant form (ADPKD) is the most common genetic cause of chronic kidney disease [1,2]. The majority of individuals with PKD eventually require renal replacement therapy .
The course and treatment of ADPKD in adults are discussed here. The diagnosis, genetics and pathogenesis of ADPKD, and autosomal recessive PKD in children are discussed elsewhere. (See "Diagnosis of and screening for autosomal dominant polycystic kidney disease" and "Genetics of autosomal dominant polycystic kidney disease and mechanisms of cyst growth" and "Autosomal recessive polycystic kidney disease in children".)
Autosomal dominant PKD (ADPKD) occurs in all races and has a reported prevalence of 1:400 to 1:1000 . ADPKD is the underlying cause of kidney disease in approximately five percent of patients who initiate dialysis annually in the United States [4,5].
ADPKD is caused by mutations of either PKD1 (which encodes polycystin-1) on chromosome 16 or PKD2 (which encodes polycystin-2) on chromosome 4 . PKD1 mutations are more common (approximately 85 percent) than PKD2 mutations (approximately 15 percent). The relative frequency of PKD1 and PKD2 mutations depend on the age of the population being studied since patients with PKD2 mutations present at an older age and progress more slowly than patients with PKD1 mutations. As a result, PKD2 mutations may be underreported compared to PKD1, and the frequency of PKD2 underestimated among populations in which only symptomatic individuals are tested. This is demonstrated by the following:
- PKD1 mutations were present in 85 percent and PKD2 mutation in 15 percent of cases, respectively, in a study of patients who had known PKD . By contrast, the frequency of PKD2 mutations was higher (27 percent) in population-based studies that included individuals who were at risk for ADPKD but had no evidence of clinical renal disease [3,6].
- Since patients with PKD1 reach end stage renal disease or die at a younger age compared to those with PKD2 , studies of older patients with ADPKD demonstrate a higher proportion of disease attributable to PKD2 [2,8]. In a study of 46 patients with ADPKD who had not yet started dialysis by age 63, 18 had mutations of PKD2. This contrasts to only 4 of the 40 patients with ADPKD younger than age 63 who served as a control group . (See "Genetics of autosomal dominant polycystic kidney disease and mechanisms of cyst growth".)