Subclinical Primary Aldosteronism and eGFR Decline Over Time

KEY POINTS: This prospective study of 976 adults measured the association between subclinical primary aldosteronism and kidney outcomes. Among a general healthy adult population, subclinical primary aldosteronism was associated with steeper decline in eGFR over time. Primary aldosteronism pathophysiology spans a wide unrecognized continuum that parallels the risk for kidney disease. BACKGROUND: Primary aldosteronism, an overt form of renin-independent aldosterone production, leads to steeper eGFR decline compared with primary hypertension. Mounting evidence suggests that milder forms of renin-independent aldosterone production (subclinical primary aldosteronism) are highly prevalent; however, the link between subclinical primary aldosteronism and eGFR decline remains unknown. METHODS: This prospective cohort study included 976 Canadian adults aged 40-69 years, with predominantly normal BP or mild untreated hypertension, from the randomly sampled, population-based CARTaGENE cohort. Aldosterone and renin concentrations were measured at enrollment (2009-2010). Creatinine and cystatin C were measured at enrollment and 5-7 years postenrollment. Multivariable linear mixed regression models were used to measure the associations of aldosterone, renin, and the aldosterone-to-renin ratio (ARR) with eGFR decline over time. RESULTS: The mean (SD) age of participants was 53 (7) years; 51% were female. Mean BP was 121 (15)/72 (10) mm Hg, and 11% had BP ≥140/90 mm Hg. Mean eGFR CrCysC was 109 (16) ml/min per 1.73 m 2 . At higher ARR levels, there was steeper mean eGFR decline over time (Tertile 1 [ARR, ≤0.49 ng/dl per mU/L]: -1.40 [1.77] ml/min per 1.73 m 2 /yr, Tertile 2 [ARR, 0.50-0.87 ng/dl per mU/L]: -1.48 [1.75] ml/min per 1.73 m 2 /yr, Tertile 3 [ARR, >0.87 ng/dl per mU/L]: -1.57 [1.79] ml/min per 1.73 m 2 /yr; P = 0.01), representing 11% steeper decline in the highest versus lowest ARR tertile. At lower renin levels, there was steeper mean eGFR decline over time (Tertile 1 [renin, ≤9.2 mU/L]: -1.59 [1.80] ml/min per 1.73 m 2 /yr, Tertile 2 [renin, 9.3-15.9 mU/L]: -1.53 [1.77] ml/min per 1.73 m 2 /yr, Tertile 3 [renin, >15.9 mU/L]: -1.33 [1.72] ml/min per 1.73 m 2 /yr; P = 0.04), representing 16% steeper eGFR decline in the lowest versus highest renin tertile. There was no significant association between aldosterone and eGFR change over time ( P = 0.50). All aforementioned associations were independent of BP and were consistent among participants with normal BP in isolation. CONCLUSIONS: Independent of BP, elevated ARR and suppressed renin were associated with steeper eGFR decline over time. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2026_04_30_ASN0000001039.mp3.