The pivotal role of melatonin in ameliorating chronic kidney disease by suppression of the renin-angiotensin system in the kidney

Melatonin is a hormone produced by the pineal gland, predominantly at night, and plays a pivotal role in regulating the circadian rhythm as well as a variety of biological functions, including anti-inflammation, anti-oxidation, inhibition of sympathetic nerve activity, and preservation of endothelial cell function. The intrarenal renin-angiotensin system (RAS) is one of the most important contributors in the pathophysiology of chronic kidney disease (CKD) and hypertension, independent of the circulating RAS, due to sodium reabsorption and inflammation and fibrosis in the kidney. However, the relationship between melatonin secretion and intrarenal RAS activation has remained unknown. It has been recently shown that impaired nighttime melatonin secretion is associated with nighttime urinary angiotensinogen excretion, a surrogate marker of intrarenal RAS activation and renal damage in patients with CKD. Moreover, it has also been indicated that melatonin administered exogenously exercises antioxidant effects that ameliorate intrarenal RAS activation and renal injury in chronic progressive CKD animal models. As a result, the new roles of melatonin in suppressing RAS in the kidney via amelioration of reactive oxygen species have been clarified. Therefore, we review the relationship between melatonin and intrarenal RAS activation and indicate the possibility of a new strategy to suppress CKD, which is a risk factor for cardiovascular and end-stage renal diseases.