European Primary Care Cardiovascular Society

Kidney outcomes reduced by non-steroidal MRA in CKD and T2DM

Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes

Literature - Bakris GL, Agarwal R, Anker SD, et al. - N Eng J Med, 2020, DOI: 10.1056/NEJMoa2025845

Introduction and methods

Clinical strategies for the management of CKD in patients with T2DM include treatment with an angiotensin receptor blocker (ARB) or an angiotensin-converting-enzyme (ACE) inhibitor, or a sodium glucose co-transporter (SGLT2) inhibitor to control hypertension and hyperglycemia [1,2]. However, a risk of CKD progression still remains, showing the need for newer therapies.

Aldosterone binds to the mineralocorticoid receptor (MR), leading to sodium absorption and potassium excretion, thereby controlling fluid and electrolyte status as well as blood pressure. Overactivation of the MR has been associated with the development of cardiorenal diseases such as CKD and diabetes, through increased levels of inflammatory cytokines and profibrotic factors [3]. Although a meta-analysis showed a reduction of 31% in urinary protein or albumin excretion after steroidal MR-antagonist (MRA) treatment in patient with CKD, data on hard clinical outcomes are lacking [4].

The dihydropyridine finerenone is a nonsteroidal, selective antagonist of the MR, and showed in preclinical models, more potent anti-inflammatory and antifibrotic effects than steroidal MRAs [5-8]. Also, patients with T2DM and CKD treated with finerenone had reduced albumin-to-creatinine ratio compared to those treated with a RAS blocker and smaller effects on serum potassium levels compared to those treated with spironolactone [9,10].

This study assessed the long-term efficacy and safety of finerenone on kidney and CV outcomes in patients with advanced CKD and T2DM.

The phase 3 Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) trial was a double-blind, placebo-controlled, randomized (1:1), multicenter trial. Patients (n=5674, ≥18 years) diagnosed with type 2 diabetes and CKD receiving an ACE-inhibitor or ARB medication at maximum tolerable dose were included in the study and randomized to finerenone or placebo. Baseline potassium concentration levels had to be 4.8 mmol/L or less and eGFR levels had to be stable. CKD was defined as persistent moderately elevated albuminuria (urinary albumin-to-creatinine ratio [UACR] of 30 to <300 mg/g) and an eGFR of 25 to <60 mL/min/1.73m² and a history of diabetic retinopathy or persistent, severely elevated albuminuria (UACR of 300-5000 mg/g) and a eGFR of 25-<75 mL/min/1.73m². The primary outcome was a composite of kidney failure defined as end-stage kidney disease (dialysis ≥90 days or kidney transplantation) or an eGFR <15mL/min/1.73m², sustained decrease of ≥40% of eGFR in ≥4 weeks, or renal death. The secondary CV outcome was a composite of CV death, non-fatal MI, non-fatal stroke, or HF hospitalization. Other secondary outcomes were all-cause death, change in UACR from baseline to 4 months and a composite of kidney failure, sustained decrease of ≥57% of eGFR from baseline for a minimum of 4 weeks or renal death. Median follow-up was 2.6 years.

Main results

Conclusion

Patients with T2DM and CKD, who received finerenone had a significant lower risk of a primary kidney event compared to patients treated with placebo. In addition, a composite of CV events was reduced by finerenone in these patients when compared to placebo.

References

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Find this article online at New Eng J Med.

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