Autosomal dominant polycystic kidney disease: modification of disease progression

Autosomal dominant polycystic kidney disease is a common inherited disorder , which is characterised by the formation of fluid-filled cysts in both kid neys that leads to progressive renal failure. Mutations in two genes, PKD1 and PKD2, are associated with the disorder. We describe the various factors that cause variation in disease progression between patients. These includ e whether the patient has a germline mutation in the PKD1 or in the PKD2 ge ne, and the nature of the mutation. Detection of mutations in PKD1 is compl icated, but the total number identified is rising and will enable genotype- to-phenotype studies. Another factor affecting disease progression is the o ccurrence of somatic mutations in PKD genes. Furthermore, modifying genes m ight directly affect the function of polycystins by affecting the rate of s omatic mutations or the rate of protein interactions, or they might affect cystogenesis itself or clinical factors associated with disease progression . Finally, environmental factors that speed up or slow down progress toward s chronic renal failure have been identified in rodents.