THE ROLE OF MTOR INHIBITION IN THE CONTROL OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Autosomal dominant polycystic kidney disease (ADPKD), the most common type of genetic kidney disease, affects more than 12 million people worldwide. Effective therapies for ADPKD are desperately needed. Persistent progress has been made in the understanding of processes that are responsible for renal cyst formation and progression of ADPKD. Cellular pathways that involve polycystins, intracellular calcium and cAMP regulation, and the serine/threonine-protein kinase mTOR (mammalian target of rapamycin) pathway have been characterized. The understanding of the ADPKD phenotype at the cellular level and the encouraging results in experimental models of polycystic kidney disease have laid the foundation for the development of clinical trials and potentially effective targeted treatments. This review addresses the current knowledge about the pathogenesis of the disease and the overwhelming evidence in support of mTOR as a common molecular pathway for cystogenesis. The recent advances and challenges in understanding the role of mTOR inhibitors in controlling ADPKD in animal models and clinical trials will be discussed.