Subclinical Primary Aldosteronism as a Common Accelerator of Kidney Function Decline: Evidence from a Population-Based Cohort

Background: Primary aldosteronism (PA) is a renin-independent cause of hypertension that accelerates decline in kidney function more than essential hypertension. Milder forms of this phenotype, called “subclinical PA,” are common, but their association with kidney function decline remains unknown. We evaluated whether subclinical PA is associated with steeper decline in kidney function in a population-based cohort. Methods: We conducted a prospective cohort study of 976 adults aged 40-69 years from CARTaGENE, a population-based cohort in Québec, Canada. At enrollment (2009–2010), plasma aldosterone and renin were measured to calculate the aldosterone-to-renin ratio (ARR). Serum creatinine and cystatin C were measured at baseline and again 5-7 years later to estimate eGFR using the 2021 CKD-EPI creatinine-cystatin C equation. The annual rate of eGFR decline was calculated for each participant. Multivariable linear regression models measured associations between ARR, renin, and aldosterone levels and eGFR decline, adjusting for a priori demographic and clinical covariates. Results: Participants had a mean (SD) age of 53 (7) years; 51% were female. Mean blood pressure was 121/72 mmHg and mean (SD) baseline eGFRCrCysC was 109 (16) mL/min/1.73m2. Higher ARR was associated with steeper median annual eGFR decline across tertiles (T1: −1.21 [−0.25 to −2.43], T2: −1.39 [−0.45 to −2.33], T3: −1.52 [−0.55 to −2.47] mL/min/1.73m2/year; p=0.04), representing a 21% steeper decline in the highest vs. lowest tertile. Lower renin was similarly associated with faster decline (T1: −1.50 [−0.58 to −2.50], T2: −1.41 [−0.31 to −2.43], T3: −1.17 [−0.32 to −2.15]; p=0.01), corresponding to a 22% steeper eGFR decline in the lowest vs. highest renin tertile. Aldosterone levels alone were not significantly associated with eGFR decline. All associations were independent of blood pressure. Conclusion: In this prospective population-based study, the presence and magnitude of subclinical primary aldosteronism were independently associated with steeper decline in estimated glomerular filtration rate. These findings challenge the traditional approach of treating PA as a categorical disease and suggest that early detection and targeted intervention may help mitigate kidney and cardiovascular risk in this common, underrecognized population. Funding: Private Foundation Support, Government Support – Non-U.S.

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