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Mechanism-based therapeutics for autosomal dominant polycystic kidney disease: recent progress and future prospects.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, accounting for up to 10% of patients on renal replacement therapy. There are presently no proven treatments for ADPKD and an effective disease-modifying drug would have significant implications for patients and their families. Since the identification of PKD1 and PKD2, there has been an explosion in knowledge identifying new disease mechanisms and testing new drugs. Currently, the three major treatment strategies are to: (1) reduce cAMP levels; (2) inhibit cell proliferation, and (3) reduce fluid secretion. Several compounds shown to be effective in preclinical models have already undergone clinical trials and more are planned. In addition, a whole raft of other compounds have been developed from preclinical studies. The purpose of this paper is to evaluate the results of recent published trials, review current trials and highlight the most promising compounds in the pipeline. There appears to be no shortage of potential candidates, but several key issues need to be addressed to facilitate clinical translation.

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