The kidney not only regulates fluid and electrolyte balance but also functions as an endocrine organ. For instance, it is the major source of circulating
erythropoietin and
renin. Despite currently available
therapies, there is a marked increase in cardiovascular morbidity and mortality among patients suffering from
end-stage renal disease. We hypothesized that the current understanding of the endocrine function of the kidney was incomplete and that the organ might secrete additional
proteins with important
biological roles. Here we report the identification of a novel
flavin adenine dinucleotide-dependent
amine oxidase (
renalase) that is secreted into the blood by the kidney and metabolizes
catecholamines in vitro (
renalase metabolizes
dopamine most efficiently, followed by
epinephrine, and then
norepinephrine). In humans,
renalase gene expression is highest in the kidney but is also detectable in the heart, skeletal muscle, and the small intestine. The plasma concentration of
renalase is markedly reduced in patients with
end-stage renal disease, as compared with healthy subjects.
Renalase infusion in rats caused a decrease in cardiac contractility, heart rate, and blood pressure and prevented a compensatory increase in peripheral vascular tone. These results identify
renalase as what we believe to be a novel
amine oxidase that is secreted by the kidney, circulates in blood, and modulates cardiac function and systemic blood pressure.