Serum Aldosterone Levels Could Predict Chronic Kidney Disease Progression

Ashish Verma, MD

An analysis of data from the Chronic Renal Insufficiency Cohort (CRIC) is providing clinicians with an overview of the impact of aldosterone levels on risk of worsening chronic kidney disease (CKD) among patients with CKD.

With a decade of follow-up data suggesting each doubling of aldosterone was linked to an 11% increase in risk of CKD progression, investigators suggest the results provide evidence backing use of the nonsteroidal MRA finerenone (Kerendia) for reducing the risk of CKD progression in these patients.

“These findings are important as they suggest that higher concentrations of aldosterone may play a role in CKD progression and cardiovascular disease in patients with CKD. This study provides evidence for the mechanism by which mineralocorticoid receptor antagonists could delay CKD progression and supports investigating their value in patients without diabetes,” said lead investigator Ashish Verma, MD, assistant professor at Boston University School of Medicine, in a statement.

As both fields have advanced in recent years, role of cardiologists and nephrologists become more intertwined. Now, thanks to advances in pharmacological therapies, the intersectionality of cardiovascular and nephrotic conditions has been transformed. With an interest in learning more about how the mechanism of action for MRAs in delaying CKD progression, Verma and a trio of colleagues from Boston-based institutions conducted the current study with the intent of assessing how aldosterone levels may impact CKD progression in patients with or without diabetes.

To do so, investigators designed the present study as an observational cohort analysis of data from 3680 participants aged 21-74 years enrolled within the CRIC study from April 8, 2003-September 3, 2018. Exclusion criteria for the present study included inability to provide written consent, institutionalization, pregnancy, enrollment in other studies, and being classified as New York Heart Association Classes III–IV heart failure, among others.

The primary outcome of interest for the observational cohort analysis was CKD progression, which was defined as a composite of 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, whichever occurred first. Investigators pointed out Cox proportion hazard models were used to estimate associations between serum aldosterone levels and CKD outcomes.

The 3680-patient cohort identified for inclusion had a mean age of 58.1 (SD, 11.1) years, 44.7% were female, 46.8% were White, 41.2% were Black, 86% had hypertension, 82% had a history of hypercholesterolemia, and the mean eGFR was 44.3 (SD, 15.0) mL/min/1.73m2. At baseline, higher aldosterone concentrations were associated with a lower eGFR, lower serum potassium, greater urinary potassium, and protein excretion. During a follow-up period lasting a median of 9.6 years, 1412 individuals developed the composite outcome of CKD progression and 1129 individuals developed end-stage kidney disease.

Initial analysis revealed those who developed the composite CKD outcome had a median baseline serum aldosterone concentration that was greater than those who did not develop the composite outcome or were censored for loss to follow-up or death (10.6 vs 9.6 ng/dL; P <.001). In adjusted models, results suggested each doubling in serum aldosterone levels was associated with an 11% increase in risk of CKD progression (HR, 1.11 [95% CI, 1.04-1.18]).

In fully adjusted analyses, those in the highest quartile of serum aldosterone had a 45% increased risk of CKD progression (HR, 1.45 [95% CI; 1.22–1.73]) compared to those in the lowest quartile. Investigators highlighted the risk for CKD progression was similar regardless of whether patients had concomitant diabetes (P-interaction=.10). In additional analyses assessing associations of serum aldosterone and all-cause mortality, which included 11.5 years of follow-up data, results indicated those win the highest quartile of serum aldosterone had a 22% greater risk of all-cause mortality (HR, 1.22 [95% CI, 1.02-1.45]) compared to those in the lowest quartile.

“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. 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,” wrote George Bakris, MD, of the University of Chicago Medicine, in an accompanying editorial.

This study, “Aldosterone in chronic kidney disease and renal outcomes,” was published in the European Heart Journal.