Purpose of review: Renalase is a secreted amine oxidase that is synthesized in the kidney, and that metabolizes circulating catecholamines. Tissue and plasma renalase levels are decreased in models of chronic kidney disease. Recent data indicate that renalase deficiency is associated with increased blood pressure and elevated circulating catecholamines. The mechanisms of hypertension in renalase deficiency and the possibility that renalase regulates the renal dopamine system are discussed.
Recent findings: Characterization of the renalase knockout mouse model revealed that renalase deficiency increases SBP and DBP. Renal and cardiac functions are unaffected, but there is evidence of sympathetic activation, with elevation of plasma and urine catecholamines. Renalase is continually excreted in urine, and is enzymatically active and could modulate catecholamines levels in tubular fluid. Renalase expression is modulated by salt intake, and recombinant renalase has a potent and prolonged hypotensive effect on blood pressure in Dahl salt-sensitive rats and rats with chronic kidney disease. Plasma renalase levels are inversely associated with SBP in patients with resistant hypertension. A functional mutation in renalase (Glu37Asp) associated with essential hypertension also predicts more severe cardiac hypertrophy, dysfunction, and ischemia in individuals with stable coronary artery disease, comparable blood pressure and normal renal function.
Summary: Urinary renalase metabolizes urinary catecholamines, and perhaps regulates dopamine concentration in luminal fluid, and modulate proximal tubular sodium transport. Renalase deficiency is associated with increased sympathetic tone and resistant hypertension. Recombinant renalase is a potent antihypertensive agent in Dahl salt-sensitive rats and in rats with chronic kidney disease.