Targeted Therapies for Autosomal Dominant Polycystic Kidney Disease.

摘要: Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening genetic in humans, affecting approximately 1 500 people. ADPKD characterized by cyst growth leading to progressive parenchymal damage and underlying pathology 10% of patients requiring hemodialysis or transplantation for end-stage disease. The two proteins that are mutated ADPKD, polycystin-1 polycystin-2, form a complex located on primary cilium plasma membrane facilitate calcium ion release cell. There currently no Food Drug Administration (FDA)-approved therapy cure slow progression Rodent models do not completely mimic human disease, therefore preclinical results have always successfully translated clinic. Moreover, toxicity many these potential therapies has led patient withdrawals from clinical trials. Results Here, we review compounds trial treating examine feasibility using kidney-targeted approach, with broadening therapeutic window, decreasing treatment-associated increasing efficacy agents demonstrated activity animal models. We make recommendations integrating kidney- targeted current treatment regimes, achieve combined approach ADPKD. Conclusion Many yet, date, none FDA-approved this Patients could benefit efficacious pharmacotherapy, especially if it can be kidney-targeted, intensive efforts continue focused goal.