MRA Users Less Likely To Experience Progression of Chronic Kidney Disease

An analysis of real-world data from more than 3000 patients with chronic kidney disease suggests long-term mineralocorticoid receptor antagonist (MRA) use was associated with improved renal prognosis.

A retrospective cohort study of patients from Osaka University Hospital in Japan treated between 2005 and 2018, results of the study indicate MRA use was significantly associated with a 28% lower rate of renal replacement therapy, with this relationship being dose-dependent and consistent across patient subgroups.

“The present results suggest that the clinical benefit of MRA use may extend to MRA subtypes other than finerenone. The present study spotlights MRA use by nephrologists, which can reinforce conventional treatment plans in patients with CKD not on dialysis,” wrote investigators.

Citing a lack of information on the renoprotective effects of MRA use and the recent revelations surrounding the benefits of finerenone, a team of investigators from Osaka University sought to assess the association between MRA use and risk of disease progression within a cohort from the department of nephrology within the university hospital from January 2005-December 2018. For inclusion in the study, patients needed to have an eGFR of 10 or more but less than 60 mL/min/1.73m² and follow-up of at least 90 days.

The exposure of interest was MRA use. Investigators noted MRA use was treated as a binary time-dependent variable and the clinically available MRAs in Japan were spironolactone, eplerenone, and potassium canrenoate. The primary outcome of interest was renal replacement therapy initiation, which investigators defined as initiation of chronic hemodialysis, peritoneal dialysis, or kidney transplantation. The study also included secondary outcomes, which were a composite of death from any cause and renal replacement therapy initiation and a composite of an eGFR of below 15 mL/min/1.73m2 and renal replacement therapy initiation.

A total of 3747 outpatients were identified for potential inclusion. After exclusion of those younger than 20 years of age and those without adequate follow-up, investigators identified a cohort of 3195 patients for inclusion in their analyses.

The study cohort had a median age of 66 years at baseline, 65.1% were men, and 41.3% had diabetes. The median baseline eGFR of the cohort was 38.4 mL/min/1.73m² and the median follow-up was 5.9 (IQR, 2.9-9.9) years. During the follow-up period, 770 patients received MRAs, 211 died, and 478 initiated renal replacement therapy.

Using inverse probability of weighted-weight pooled logistic regression model, investigators determined MRA use was significantly associated with a 28% lower rate of renal replacement therapy initiation (HR, 0.72 [95% CI, 0.53-0.98]) and a 24% lower rate of the composite of renal replacement therapy initiation and death (HR, 0.76 [95% CI, 0.59-0.99]). Investigators pointed out the association between MRA use and renal replacement therapy initiation was dose-dependent (P for trend <.01) and consistent across subgroups.

Further analysis indicated MRA use was associated with a lower risk of progression of proteinuria (HR, 0.75 [95% CI, 0.59-0.95]) and an increase in incidence of hyperkalemia (HR, 1.14 [95% CI, 0.88-1.48]), but this association was not statistically significant. Investigators also noted no significant associations were observed between use of statins, warfarin, DOACs, and nitrates with renal replacement therapy initiation.

In sensitivity analyses, reclassifying patients receiving MRAs for less than 1 year produced a stronger association with renal replacement therapy initiation, with a 42% lower rate of initiation for MRA users (HR, 0.58 [95% CI, 0.40-0.85]). Additionally, analyses where MRA use was refined as spironolactone only suggested a similar association.

“Even after adjustment for time-varying confounding, MRA use was found to be associated with lower risks of kidney failure with replacement therapy and the composite of death and kidney failure with replacement therapy. This association was consistently observed in patients without diabetes and those with advanced CKD, who were not included in FIDELIO-DKD,” wrote investigators.

This study, “Mineralocorticoid Receptor Antagonist Use and Hard Renal Outcomes in Real-World Patients with Chronic Kidney Disease,” was published in Hypertension.