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.

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