Renalase, a new renal hormone: its role in health and disease.

PURPOSE OF REVIEW: Renalase is a secreted amine oxidase that metabolizes catecholamines. The approach used to identify this novel renal hormone will be discussed, as will the experimental data suggesting it regulates cardiovascular function, and its deficiency contributes to heightened cardiovascular risks in patients with chronic kidney disease.

RECENT FINDINGS: The sympathetic nervous system is activated in chronic kidney disease and end-stage renal disease, and patients have a significant increase in cardiovascular disease. Parenteral administration of either native or recombinant renalase lowers blood pressure and heart rate by metabolizing circulating catecholamines. Plasma levels are markedly reduced in patients with chronic kidney disease and end-stage renal disease. Renalase deficiency occurs in salt-sensitive Dahl rats as they develop hypertension. Renalase inhibition by antisense RNA increases baseline blood pressure, and leads to an exaggerated blood pressure response to adrenergic stress. Most recently, two single nucleotide polymorphisms in the renalase gene were found to be associated with essential hypertension in humans.

SUMMARY: The renalase pathway is a previously unrecognized mechanism for regulating circulating catecholamines, and, therefore, cardiac function, and blood pressure. Abnormalities in the renalase pathway are evident in animal models of chronic kidney disease and hypertension. Collectively, these data suggest that renalase replacement may be an important therapeutic modality.