Renin-Aldosterone Profiles and Cardiorenal Outcomes in Hypertension: A Nationwide Cohort Study.

Abstract (English)

BACKGROUND: Renin-independent aldosterone production may contribute to adverse cardiorenal outcomes, but population-based evidence remains limited. OBJECTIVES: In this study, we sought to investigate the association of renin-aldosterone profiles with cardiorenal events in adults with hypertension. METHODS: This cohort study used linked Danish health registries with complete laboratory test results from January 2017 to November 2024. All adults with hypertension selected by clinicians for aldosterone and renin testing in the study period were included. Endpoints included kidney function decline and cardiovascular outcomes. We used Cox regression and restricted cubic spline models adjusted for age, sex, index year, comorbidities, and comedications. RESULTS: Among 12,650 adults with hypertension, 1,840 (15%) had an aldosterone-to-renin ratio (ARR) of 27.7 to <70 pmol/mIU, 480 (4%) 70 to <138.7 pmol/mIU, and 310 (2%) ≥138.7 pmol/mIU. Median follow-up was 3.6 years. Higher ARR, higher aldosterone, and lower renin levels were associated with increased adjusted HRs (aHRs) of rapid kidney function decline (eGFR decrease of at least 5 mL/min/1.73 m² per year), kidney failure or ≥40% eGFR decline, and major adverse cardiovascular events (MACE) in cubic spline models. Risk of kidney function decline outcomes varied across combinations of aldosterone and renin levels, with higher risk observed in individuals with elevated aldosterone in the context of low renin. Analyses using predefined ARR levels showed similar trends. Specifically, the aHRs for rapid kidney function decline were 1.27 (95% CI: 1.17-1.38), 1.98 (95% CI: 1.75-2.25), and 2.66 (95% CI: 2.31-3.08) for ARR 27.7 to 70.0, 70.0 to 138.7, and >138.7 pmol/mIU, respectively. For kidney failure or ≥40% eGFR decline and for MACE, the aHRs were not elevated at ARR 27.7-70.0 pmol/mIU, but increased at higher ARR levels. CONCLUSIONS: Adults with hypertension and renin-independent aldosterone production are at increased risk of rapid kidney function decline as well as, at higher ARR levels, kidney failure and MACE. Although clinical practice guidelines recommend distinct thresholds for diagnosing primary aldosteronism, our findings underscore that the risk for kidney and cardiovascular outcomes in adults with hypertension manifests as a continuous gradient that parallels the magnitude of renin-independent aldosterone production.