Subclinical Primary Aldosteronism and eGFR Decline Over Time

Background: Primary aldosteronism, an overt form of renin-independent aldosterone production, leads to steeper eGFR decline compared to 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 blood pressure 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 post-enrollment. 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 blood pressure was 121 (15)/72 (10) mmHg, and 11% had blood pressure ≥140/90 mmHg. Mean eGFRCrCysC was 109 (16) mL/min/1.73m2. 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/1.73m2/year, Tertile 2 (ARR 0.50-0.87 ng/dL per mU/L): -1.48 (1.75) mL/min/1.73m2/year, Tertile 3 (ARR >0.87 ng/dL per mU/L): -1.57 (1.79) mL/min/1.73m2/year; 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/1.73m2/year, Tertile 2 (renin 9.3-15.9 mU/L): -1.53 (1.77) mL/min/1.73m2/year, Tertile 3 (renin >15.9 mU/L): -1.33 (1.72) mL/min/1.73m2/year; 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 blood pressure and were consistent among participants with normal blood pressure in isolation. Conclusions: Independent of blood pressure, elevated ARR and suppressed renin were associated with steeper eGFR decline over time.