Polycystic Kidney Disease

Polycystic Kidney Disease results from mutations in the PKD1 gene (chromosome 16, accounting for 85% of cases) or PKD2 gene (chromosome 4, accounting for 15% of cases). These genes encode proteins involved in cellular structure and communication. The mutations lead to uncontrolled cyst formation and expansion within the kidney, progressively destroying normal kidney tissue. PKD1 mutations typically cause more aggressive disease with kidney failure by age 50-60, while PKD2 mutations generally lead to later onset disease. As cysts enlarge, they damage remaining functional kidney tissue through inflammation, ischemia, and fibrosis. Most patients develop hypertension even before significant loss of kidney function, which can accelerate disease progression. Patients may have numerous complications including chronic pain from cyst hemorrhage, urinary tract infections, kidney stones, and hepatic cysts that rarely cause symptoms. About 50% of PKD1 patients develop end-stage renal disease by age 60. Extrarenal manifestations include aortic root dilation, mitral valve prolapse, intracranial aneurysms, and arachnoid cysts.