Relaxin Improves Renal Function and Decreases Cyst Progression in a Rat Model of Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disorder that affects over 600,000 Americans and is characterized by the development and growth of fluid-filled cysts, inflammation, and fibrosis within both kidneys.  These events ultimately destroy renal function and lead to end-stage renal disease.  Without a cure and few therapeutic options, identification and targeting of additional pathogenic mechanisms is crucial for the continued development of ADPKD treatment strategies.  Relaxin is a hormone essential for renal vasodilation during pregnancy.  Additionally, relaxin has anti-fibrotic and anti-inflammatory properties and regulates collagen metabolism, and multiple signaling pathways.  These same processes and signaling pathways are altered in ADPKD patients and male cystic (Cy/+) rats.  We tested the hypothesis that relaxin treatment of male Cy/+ rats will slow disease progression by increasing blood flow and limiting renal fibrosis.  We treated Cy/+ and normal male rats with synthetic relaxin or vehicle control.  Relaxin improved renal function by increasing the glomerular filtration rate.  Using immunohistochemical techniques, we identified decreases in cyst size and decreased fibroblast numbers within Cy/+ kidneys.  Relaxin receptor, RXFP1, was expressed in Cy/+ rat and human cystic renal epithelial cells, indicating that these cells are capable of ligand binding.  Current studies are focusing on gene expression profiles of molecules involved in matrix metabolism within Cy/+ kidneys and human ADPKD epithelia.  Collectively, our studies show that administration of relaxin decreases cyst growth and disease progression in a model of ADPKD by modulating matrix metabolism and identify new druggable targets that can slow progression of ADPKD.