Higher serum aldosterone levels were linked to a greater risk of kidney failure in chronic kidney disease (CKD), both for those with and without diabetes, a study showed.
Every doubling in aldosterone level was associated with 11% (95% CI 1.04-1.18) greater risk of progression of CKD to end-stage kidney disease or halving of estimated glomerular filtration rate (eGFR) over a median follow-up of 9.6 years.
The highest quartile had 45% higher risk of CKD progression than those in the lowest quartile, reported Ashish Verma, MD, of Boston University School of Medicine, and co-authors in a study published in the European Heart Journal.
Notably, the risk for CKD progression was similar regardless of whether patients had concomitant diabetes (P=0.10 for interaction).
“These findings provide mechanistic support for MR [mineralocorticoid receptor] antagonists in delaying CKD progression and suggest that they may also have a role in those without diabetes,” Verma’s group concluded.
Whether MRA drugs might have a broader role has been a question since the landmark FIDELIO-DKD and FIGARO-DKD trials showed that the nonsteroidal MRA drug finerenone (Kerendia) delayed CKD progression and reduced cardiovascular events in patients with CKD and diabetes.
The drug gained FDA approval for prevention of CKD progression based on those results — but only for diabetic patients.
Verma’s group said their study “extends the relationship between pathogenic aldosteronism and CKD progression beyond overt cases of primary aldosteronism, and beyond the development of CKD to progression of CKD, and beyond only those with diabetes.”
It’s time for trials to establish MRA therapy’s value in CKD patients without diabetes, they suggested, pointing to the FIND-CKD trial now underway to do just that.
But the results also give impetus to measuring aldosterone, argued George Bakris, MD, of the University of Chicago, and Frederic Jaisser, MD, PhD, of the Université de Paris, in an invited editorial.
“Taken together, these studies suggest that aldosterone levels need to be assessed in all patients at risk for and/or in the presence of cardiorenal disease, especially if they have central obesity and/or resistant hypertension,” wrote the editorialists. “We now have relatively safe and better-tolerated agents than traditional steroidal agents that can and should be used to reduce cardiorenal risk in these groups of patients.”
Fears of hyperkalemia that have held back long-term use of the steroidal MRA drugs in advanced CKD are largely allayed with their non-steroidal cousins, Bakris and Jaisser noted. Study discontinuation due to hyperkalemia occurred in only 1.7% of finerenone-randomized patients in the trials, compared with 0.6% on placebo after a median follow-up of 3 years.
Verma’s study utilized the Chronic Renal Insufficiency Cohort (CRIC) to analyze CKD progression in 3,680 patients with follow-ups to the initial analysis from 2003 through 2008. At that point an average of 9.6 years later, 1,412 patients developed CKD and 1,129 participants had developed end-stage kidney disease.
The average age in the cohort was 58.1 years; 46.8% of the participants were white, and 44.7% were women.
Limitations to the study included lack of data regarding the use of angiotensin receptor blockers or ACE inhibitor duration, a single measurement of serum aldosterone levels during the baseline analysis, and no data regarding albumin or renin, proteins that could act as a determining factor in high aldosterone levels.
Bakris and Jaisser also pointed out that “while plasma aldosterone is adequate to measure the level of this hormone, it should be in the context of plasma renin activity to fully assess activation of the axis. Moreover, due to increased platelet adherence of aldosterone, 24 h urine aldosterone corrected for creatinine is a more accurate way to determine aldosterone levels.”
Vaidya reported relationships with Corcept Therapeutics, Mineralys, and HRA Pharma.
Bakris disclosed relationships with Bayer, KBP Biosciences, Ionis, Alnylam, AstraZeneca, Quantum Genomics, Horizon, Novo Nordisk, DiaMedica Therapeutics, and inRegen.
Jaisser disclosed no relevant relationships with industry.