Renalase deficiency in chronic kidney disease, and its contribution to hypertension and cardiovascular disease.
OBJECTIVE
Recent experimental data shed light on the regulation of renalase, a secreted amine oxidase, which circulates in an inactive form (prorenalase). Abnormalities in the renalase pathway are evident not only in animal models of chronic kidney disease, but also during the development of hypertension, at a time when kidney function appears normal.


RESULTS
Prorenalase is rapidly (30-60 s) activated by increased plasma catecholamines and systolic blood pressure. Catecholamine administration promotes the secretion of preformed renalase within 5 min. Plasma renalase is markedly reduced in patients with chronic kidney disease and end-stage renal disease, and in animal models of chronic kidney disease and salt-dependent hypertension. Rats subjected to subtotal nephrectomy develop hypertension and chronic kidney disease, and exhibit low plasma and cardiac renalase, and abnormal renalase activation.


CONCLUSIONS
The renalase pathway is a previously unrecognized mechanism for regulating circulating catecholamines, cardiac function and blood pressure. In this pathway, prorenalase is rapidly activated by increased catecholamines and converted to renalase, which in turn degrades catecholamines. Abnormalities in the renalase pathway are evident in animal models of chronic kidney disease and hypertension. Collectively, these data suggest that renalase plays a key role in the regulation of sympathetic tone, blood pressure and cardiac function.
Desir
Gary V
GV
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8029, USA. gary.desir@yale.edu
D000818:Animals; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D002395:Catecholamines / Q000097:blood; D002908:Chronic Disease; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000097:blood / Q000172:deficiency*; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D007668:Kidney / Q000201:enzymology*; D007674:Kidney Diseases / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology; D008995:Monoamine Oxidase / Q000097:blood / Q000172:deficiency*
D002395:Catecholamines; D004792:Enzyme Precursors; D008995:Monoamine Oxidase; C521557:renalase