Renalase is a novel renal hormone that regulates cardiovascular function

Patients with chronic kidney disease suffer from a significant increase in cardiovascular morbidity and mortality. While the reasons for this observation are not entirely clear, it is generally accepted that current methods of renal replacement therapy do not adequately mimic the various roles of the kidney, and that the diseased kidney may generate signals that affect other systems with detrimental consequences. We hypothesized that the kidney synthesized proteins, which were unrecognized, but were secreted in the circulation and modulated the cardiovascular system. To gain a fuller understanding of the process, we embarked on a search for novel, secreted renal proteins, using a number of complementary approaches. We identified a flavin adenine dinucleotide-dependent amine oxidase (renalase) that is made and secreted by the kidney. Renalase blood levels are easily measured in healthy subjects, but are markedly reduced in patients with end-stage renal disease. In vitro studies indicate that renalase is a novel amine oxidase that specifically metabolizes circulating catecholamines including epinephrine and norepinephrine. Renalase infusion leads to a decrease in cardiac contractility, heart rate, and blood pressure and prevented a compensatory increase in peripheral vascular tone. These results identify renalase as a novel renal hormone that modulates cardiac function and systemic blood pressure by regulating catecholamine levels. Since patients with chronic kidney disease have increased sympathetic tone and decreased renalase blood level, we speculate that renalase administration will improve cardiovascular outcome in this patient population.