Save Those Kidney Beans: Nephroprotective Effects of Finerenone for Patients With Diabetes

In a past Talking Therapeutics column, Dr Jennings opined the nephroprotective effects of SGL2 inhibitors for patients with CKD. In this week’s column, he continues the kidney-focused theme with an exposé on finerenone—a novel, highly selective mineralocorticoid receptor (MR) antagonist.

Point 1: Finerenone can save the kidneys

Finerenone is a third-generation potent, specific, orally bioavailable, non-steroidal MR antagonist. While it’s structurally a dihydropyridine, it has no activity on L-type calcium channels. Like epleronone, finerenone is >500-fold more selective for the MR than steroid receptors (like estrogen and progesterone). While traditional steroid-based MR antagonists typically build up to higher concentrations in the kidney vs the heart, a property that may contribute to hyperkalaemic side effects, finerenone achieves an equivalent distribution between cardiac and renal compartments.

The FIDELIO-CKD study¹ evaluated the effect of finerenone on CKD outcomes in type 2 Diabetes. Researchers in this study of over 5000 CKD patients (who were already on max tolerated ACE/ARB therapy) found that the primary composite outcome (kidney failure, sustained decrease of 40% in the eGFR from baseline, or death from renal causes) for finerenone vs placebo was 17.8% vs 21.1% (P=.0014). Rates of drug discontinuation due to hyperkalemia were double with finerenone vs placebo, and importantly an estimated 5% of patients were also taking a SGLT2 inhibitor.

Point 2: Finerenone also protects the heart

While not the primary focus of the FIDELIO-CKD trial, secondary analysis² pointed towards a cardiovascular protective effect. Rates of cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure were 13% for finerenone vs 14.8% for placebo (P=.03). These findings are salient as they were recently confirmed in a May 17report³ from Healio about the FIGARO-DKD trial, which showed that finerenone significantly reduced the composite risk of time to first occurrence of cardiovascular death or non-fatal CV events, defined as myocardial infarction, stroke, or hospitalization for heart failure. FIGARO, which included more patients with earlier stage CKD and type 2 diabetes, was the second large phase 3 trial demonstrating favorable cardiovascular outcomes.

Finally, in FEDELIO-CKD⁴ there also appeared to be a reduction in incident atrial fibrillation or flutter with finerenone in this patient population. This finding is hypothesis generating and will likely need to be further validated; however, I expect these findings will be confirmed with further study, as a similar benefit has been reported with eplerenone (but not with spironolactone).

References:

1. Bakris G, Agarwal R, Anker S et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. New England Journal of Medicine. 2020;383(23):2219-2229. doi:10.1056/nejmoa2025845
2. Filippatos G, Anker S, Agarwal R et al. Finerenone and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes. Circulation. 2021;143(6):540-552. doi:10.1161/circulationaha.120.051898
3. Schaffer R. FIGARO-DKD: Finerenone reduces CV death risk in diabetic kidney disease. Healio.com. https://www.healio.com/news/endocrinology/20210512/figarodkd-finerenone-reduces-cv-death-risk-in-diabetic-kidney-disease. Published 2021. Accessed June 2, 2021.
4. Filippatos G, Bakris G, Pitt B et al. Finerenone reduces onset of atrial fibrillation in patients with chronic kidney disease and type 2 diabetes. J Am Coll Cardiol. 2021. doi:10.1016/j.jacc.2021.04.079

Dr Jennings is currently an Associate Professor of Pharmacy at Long Island University and the clinical pharmacist for the Heart Transplant and LVAD teams at New York- Presbyterian Hospital Columbia University Irving Medical Center.  He is an active researcher in his field, and he has published over 120 peer-reviewed abstracts and manuscripts, primarily focusing on the pharmacotherapy of patients under mechanical circulatory support. As a recognized expert in this area, he has been invited to speak at numerous national and international venues, including meetings in France, Saudia Arabia, and India. Finally, Dr Jennings has been active in professional organizations throughout his career. He is a fellow of the American College of Clinical Pharmacy, the American College of Cardiology, the Heart Failure Society of America, and the American Heart Association.  

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