Steroidal MRAs Provide Little Benefit, Increase Hyperkalemia Risk in Kidney Transplant Patients

Data from the American College of Physicians Internal Medicine Meeting suggests use of steroidal mineralocorticoid receptor antagonists (MRAs) offered minimal benefit and increased the risk of hyperkalemia among patients with a history of kidney transplant.

A meta-analysis of 5 randomized controlled trials of steroidal MRAs, results demonstrate patients with a history of kidney transplant receiving MRAs experienced a similar preservation in kidney function as their counterparts receiving placebo, but more than quadrupled the risk of hyperkalemia.¹

“MRAs haven no superior efficacy compared with placebo in kidney transplant recipients and are associated with a 4-fold increase in the risk of hyperkalemia despite preserved kidney function,” wrote investigators.¹

As a result of their proven safety and efficacy, MRAs, namely spironolactone and eplerenone, are 1 of the 4 pillars of guideline-directed medical therapy for heart failure with reduced ejection fraction and have been a mainstay in treatment algorithms for more than 50 years. Though neither of the aforementioned agents can lay claim to an approval for chronic kidney disease, previous research indicates MRA use could provide a renoprotective benefit.^1,2

However, as investigators of the current study point out, much less is known about the safety and efficacy of MRAs in kidney transplant recipients. With this in mind, a team led by investigators at the University of Alabama at Birmingham designed a systematic review and meta-analysis of clinical trial data recorded in the PubMed, Embase, and Cochrane databases.¹

The investigators search sought to identify clinical trials of MRAs that included kidney transplant recipients and reported on the following outcomes: glomerular filtration rate (GFR), serum creatinine, systolic (SBP) and diastolic blood pressure (DBP), hyperkalemia, and interstitial fibrosis and tubular atrophy (IFTA) scores.¹

From their search, investigators identified 5 randomized controlled trials with 293 patients who had received a kidney transplant. Among this group, 142 (48.5%) underwent treatment with a steroidal MRA. Of note, trials of finerenone (Kerendia), a nonsteroidal MRA approved for CKD with type 2 diabetes, were not included in this study.¹

The overall study cohort had a follow-up time ranging from 5 days to 36 months, approximately two-thirds were male, the mean eGFR was 54.11 (SD, 18.36) ml/min/1.73m2, and approximately two-thirds were on dialysis prior to transplant.¹

Results of the study suggested there were no significant differences between the placebo and MRA groups for in GFR (Mean Difference [MD], 0.23 mL/min/1.73 m2; 95% CI, 1.16-1.62; P = .75), serum creatinine (MD, -0.21 mg/d; 95% CI, -0.62 to 020; P = .32), SBP (MD, 0.69 mmHg: 95% CI -0.69 to 2.08; P = .33), and DBP (MD 0.45 mmHg; 95% CI -0.69 to 1.59; P = .44). Analysis of IFTA scores suggested there were no between group differences in risk of having a mild IFTA (Risk Ratio [RR], 1.21; 95% 0.83 to 1.74; P = .32), moderate IFTA (RR, 0.82; 95% CI 0.45 to 1.50; P = .51), or severe IFTA scores (RR, 0.64; P = .39).¹

Investigators highlighted use of MRAs was associated with a more than 4-fold increase in risk of hyperkalemia compared to placebo therapy (RR, 4.06: 95% CI, 1.46 to 11.28; P = .007).¹

References:

1. Dibo Paula, Mareddy NSR, Kojima GSA, et al. Efficacy and Safety of Mineralocorticoid Receptor Antagonists in Kidney Transplant Patients: An Updated Meta-Analysis of Randomized Controlled Trials. Presented at: ACP IM Meeting 2025; April 3-5; New Orleans, Louisiana.

2. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart failure: a Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18). doi: 10.1161/cir.0000000000001063