Mineralocorticoid receptor antagonists may stave off renal replacement therapy in CKD
In a real-world outpatient population, mineralocorticoid receptor antagonist use in patients with chronic kidney disease was associated with lower rates of renal replacement therapy initiation compared with nonuse, researchers reported.
According to data published in Hypertension, mineralocorticoid receptor antagonist (MRA) use in patients with an estimated glomerular filtration rate (eGFR) of 10 mL/min/1.73 m2 to 60 mL/min/1.73 m2 was tied to lower rates of chronic hemodialysis, peritoneal dialysis or kidney transplantation.
“Preventing kidney failure with replacement therapy is an ultimate treatment goal for patients with chronic kidney disease (CKD). Unfortunately, the global number of patients receiving renal replacement therapy has been increasing, despite guideline-recommended therapies for CKD, including the use of ACE inhibitors and angiotensin II receptor blockers. This may be partly because of the phenomenon of aldosterone breakthrough,” Tatsufumi Oka, of the department of nephrology at Osaka University, and colleagues wrote. “Notably, there has been a lack of real-world evidence examining the association between MRA use and hard renal outcomes, including kidney failure with replacement therapy.”
To meet this knowledge gap, Oka and colleagues conducted a retrospective study that included 3,195 adult outpatients with CKD referred to the department of nephrology at Osaka University Hospital from 2005 to 2018.
MRA use was defined as administration of spironolactone, eplerenone or potassium canrenoate. The primary outcome was renal replacement therapy initiation, defined as chronic hemodialysis, peritoneal dialysis or kidney transplantation.
MRA use in CKD
At baseline, the median age of participants was 66 years and eGFR was 38.4 mL/min/1.73 m2. During a median follow-up of 5.9 years, 770 patients received MRAs, 211 died and 478 initiated renal replacement therapy.
Researchers reported MRA use was associated with a 28% lower rate of renal replacement therapy initiation (HR = 0.72; 95% CI, 0.53-0.98; P = .039) and a 24% lower rate of the composite of renal replacement therapy initiation and death compared with nonuse (HR = 0.76; 95% CI, 0.59-0.99; P = .046).
Researchers observed a similar association favoring MRA use over nonuse for the composite of the primary outcome plus achieved eGFR less than 15 mL/min/1.73 m2 and renal replacement therapy initiation (HR = 0.75; 95% CI, 0.57-0.99; P = .045).
According to the study, MRA use was also associated with lower risk for progression of proteinuria compared with nonuse (HR = 0.75; 95% CI, 0.59-0.95).
Although the incidence of hyperkalemia was greater among patients taking MRAs, the finding was not significant (HR = 1.14; 95% CI, 0.88-1.48).
In a subsequent sensitivity analysis, researchers excluded patients who were taking MRAs for less than 1 year and observed somewhat stronger association between MRA use and replacement therapy initiation (HR = 0.58; 95% CI, 0.4-0.85).
Moreover, higher-dose MRAs were associated with greater risk reduction for replacement therapy initiation (P for trend < .01). This finding remained significant when MRA use was redefined as use of spironolactone only.
“The present study first showed that MRA use was significantly associated with a lower risk of renal replacement therapy initiation in a real-world CKD population,” the researchers wrote. “This association was consistently observed in patients with and without diabetes, those with advanced CKD, and those with overt proteinuria, some of whom were not included in the recent FIDELIO-DKD trial, which elucidated the renoprotective effect of finerenone (Kerendia, Bayer). The present study spotlights MRA use, which can reinforce conventional treatment plans for various CKD patients not on dialysis.”