What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Chronic kidney disease (CKD) (n=15817). Intervention: Nonsteroidal mineralocorticoid receptor antagonists (MRAs) vs. Placebo or eplerenone. Primary outcome: Proportion of patients with ≥40% decline in estimated glomerular filtration rate (eGFR) from baseline (RR 0.85, 95% CI 0.78, 0.92, p=<0.001).

What does this research mean for the field?

Nonsteroidal mineralocorticoid receptor antagonists significantly reduce the proportion of patients with a ≥40% decline in estimated glomerular filtration rate and lower the incidence of cardiovascular events compared to placebo in patients with chronic kidney disease. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

February 27, 2024Open Access

Efficacy and safety of nonsteroidal mineralocorticoid receptor antagonists for renal and cardiovascular outcomes in patients with chronic kidney disease: a meta-analysis of randomized clinical trials

Q: What are the key findings of this study?

Nonsteroidal mineralocorticoid receptor antagonists significantly reduced the proportion of patients with a ≥40% decline in eGFR from baseline (RR 0.85) compared to placebo in patients with chronic kidney disease.

Q: What does this research mean for the field?

Nonsteroidal mineralocorticoid receptor antagonists significantly reduce the proportion of patients with a ≥40% decline in estimated glomerular filtration rate and lower the incidence of cardiovascular events compared to placebo in patients with chronic kidney disease. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Key Result

Nonsteroidal mineralocorticoid receptor antagonists significantly reduced the proportion of patients with a ≥40% decline in eGFR from baseline (RR 0.85) compared to placebo in patients with chronic kidney disease.

Study Design

Type

Meta-Analysis (n=15,817)

Structured PICO

Do nonsteroidal mineralocorticoid receptor antagonists reduce renal and cardiovascular events in patients with chronic kidney disease?

Population

15,817 patients with chronic kidney disease (CKD) pooled from 11 RCTs

Intervention

Nonsteroidal mineralocorticoid receptor antagonists (MRAs) as a class

Comparator

Placebo or eplerenone

Outcome

Proportion of patients with ≥40% decline in estimated glomerular filtration rate (eGFR) from baselinesurrogate

Nonsteroidal MRAs significantly improve renal and cardiovascular outcomes in patients with CKD compared to placebo, though they are associated with an increased risk of hyperkalemia.

Main Result

Effect estimate: RR 0.85 (95% CI 0.78, 0.92)

p-value: p=<0.001

Limitations

Most of the RCTs were compared with the placebo group, and only two were compared with eplerenone.
The included studies comprised only published literature, excluding conference reports and other related research findings.
Only two trials had a long duration, while most other trials were of short duration.

Abstract

Objective: To systematically review the efficacy and safety of nonsteroidal mineralocorticoid receptor antagonists (MRAs) in chronic kidney disease (CKD). Methods: We systematically searched six databases to identify randomized controlled trials (RCTs) about nonsteroidal MRAs for CKD, from inception to 22 August 2023. Two reviewers independently screened the retrieved articles, extracted data, and assessed the risk of bias of included RCTs using the Cochrane risk of bias tool. We then conducted meta-analysis of the data using Stata 17.0 software. Results: 11 RCTs (n = 15,817) were included in this meta-analysis. Compared with placebo, nonsteroidal MRAs significantly reduced the proportion of patients with ≥40% decline in estimated glomerular filtration rate (eGFR) from baseline RR = 0.85, 95% CI (0.78, 0.92), p 0.001 , although the magnitude of eGFR reduction was greater WMD = −2.83, 95% CI (−3.95, −1.72), p 0.001 . The experimental group also had lower incidence of composite renal outcome RR = 0.86, 95% CI (0.79, 0.93), p 0.001 and greater reduction in urine albumin-to-creatinine ratio (UACR) from baseline WMD = −0.41, 95% CI (−0.49, −0.32), p 0.001 , as well as reduced cardiovascular events RR = 0.88, 95% CI (0.80, 0.95), p = 0.003. MRAs did not increase any adverse events compared to placebo RR = 1.00, 95% CI (0.99, 1.01), p = 0.909, but had higher incidence of hyperkalemia RR = 2.05, 95% CI (1.85, 2.280), p 0.001. Compared with eplerenone, there was no significant difference in the proportion of patients with ≥40% decline in eGFR RR = 0.57, 95% CI (0.18, 1.79), p = 0.335 or hyperkalemia RR = 0.95, 95%CI (0.48, 1.88), p = 0.875. Conclusion: Nonsteroidal MRAs can reduce the incidence of end-stage renal disease and cardiovascular adverse events in patients. Although there was still a risk of hyperkalemia compared to placebo, there was no significant difference in any adverse events compared to either placebo or eplerenone. It has become a new option for drug treatment of CKD patients, but more clinical trials are still needed to verify its efficacy and safety. Especially further direct comparison of the nonsteroidal MRAs to eplerenone in view of the relatively small number of patients reviewed are needed.

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