Vascular Complications in Autosomal Dominant Polycystic Kidney Disease: Perspectives, Paradigms, and Current State of Play.

ABSTRACT

Autosomal dominant polycystic kidney disease (ADPKD) is the leading cause of inherited kidney disease with significant contributions to CKD and end-stage kidney disease. The underlying polycystin proteins (PC1 and PC2) have widespread tissue expression and complex functional roles making ADPKD a systemic disease. Vascular complications, particularly intracranial aneurysms (ICA) are the most feared due to their potential for devastating neurological complications and sudden death. Intracranial aneurysms occur in 8-12% of all patients with ADPKD, but the risk is intensified 4-5-fold in those with a positive family history. The basis for this genetic risk is not well understood and could conceivably be due to features of the germline mutation with a significant contribution of other genetic modifiers and/or environmental factors. Here we review what is known about the natural history and genetics of unruptured ICA in ADPKD including the prevalence and risk factors for aneurysm formation and subarachnoid hemorrhage. We discuss two alternative screening strategies and recommend a practical algorithm that targets those at highest risk for ICA with a positive family history for screening.