mTOR inhibition in autosomal-dominant polycystic kidney disease (ADPKD): the question remains open

Extract

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common heritable kidney disorder with a prevalence of 1 in 400 to 1 in 1000 and accounting for ∼5% of the patient population requiring maintenance dialysis [1, 2]. Polycystins are required for the maintenance of differentiated epithelium, are expressed in kidney, liver and pancreas tubular cells, vascular smooth muscle cells and endothelium and play a role in multiple signalling pathways [3]. Disturbance of function results in increased tubular cell proliferation and apoptosis, fluid secretion resulting in progressive renal cyst formation and proliferation [1]. Mutations of the PKD1 gene, encoding polycystin-1, a membrane receptor, account for 85% of cases. A further 15% of cases are due to mutations of the PKD2 gene, encoding polycystin-2, a calcium-permeable channel binding polycystin-1. In general, PKD1 disease is associated with a more severe clinical phenotype than PKD2, with earlier onset of end-stage kidney disease (mean age 54 years compared with 74 years) and greater numbers of renal cysts [1, 4, 5].