Non-steroidal mineralocorticoid antagonists: Prospects for renoprotection in diabetic kidney disease

Abstract

Diabetic kidney disease (DKD) is the major cause of kidney failure in the world and the combination of DKD and diabetes mellitus contributes to an additive incidence of worsening cardiovascular mortality rates. Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) remain the mainstay of therapy and have reduced kidney function decline in DKD from 8 to 10 to ~4 mL/min/y. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, in the presence of ACE inhibitors or ARB agents, further slowdown DKD progression by an additional 58% to 1.8 mL/min/y. Moreover, SGLT2 inhibitors reduce heart failure risk. However, the normal rate of kidney function decline in humans is between 0.7 and 0.9 mL/min/y, hence, there is still room for improvement. Mineralocorticoid receptor antagonists (MRAs) already have a track record of benefit in heart failure risk reduction, and efficacy in reducing albuminuria and treating resistant hypertension; however hyperkalaemia and other adverse effects preclude their routine use in DKD. Novel non-steroidal MRAs offer a reduced risk of hyperkalaemia, and yet have many benefits that they share with their steroidal cousins. This paper reviews the data for both steroidal and non-steroidal MRAs in DKD and presents some data from soon-to-be-completed ongoing renal and cardiovascular outcome trials in DKD.