Kidney function predicts new-onset cardiorenal events and mortality in primary aldosteronism: approach of the 2021 race-free eGFR equation

Abstract

Individuals with primary aldosteronism (PA) exhibit glomerular hyperfiltration, which may conceal underlying kidney damage. This observational cohort study enrolled 760 coronary artery disease-naive patients diagnosed with PA between January 1, 2007 and December 31, 2018 (male, 45%; mean age, 52.3 ± 11.9 years). The baseline estimated glomerular filtration rate (eGFR) was calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which includes serum creatinine and cystatin C but omits the race variable. During a mean follow-up of 5.8 ± 3.2 years, new-onset composite cardiovascular events (total death, non-fatal myocardial infarction, and coronary revascularization procedure) occurred at a crude incidence rate of 10.9 per 1,000 person-years. Multivariable Cox proportional hazards analysis showed that baseline eGFR was independently associated with composite cardiovascular events (hazard ratio [HR], 0.98 [95% CI, 0.97-0.99]). Penalized splines smoothing in multivariable regression analysis demonstrated that the risk of composite cardiovascular events increased negatively and linearly when patients had a baseline eGFR less than 85 mL/min/1.73 m². Patients with baseline eGFR <85 mL/min/1.73 m² were independently associated with higher risks of composite cardiovascular events (HR, 2.39 [95% CI, 1.16-4.93]), all-cause mortality (HR, 4.63 [95% CI, 1.59-13.46]), and adverse kidney events (sub-distribution HR, 5.96 [95% CI, 3.69-9.62], with mortality as a competing risk). Our data support baseline eGFR as a predictor for new-onset adverse cardiorenal events and emphasizes the importance of the early detection of kidney function impairment in hypertensive patients with PA. We also firstly validate the 2021 race-free CKD-EPI eGFR equation in Asian patents with PA. Even with the glomerular hyperfiltration phenomenon, baseline eGFR in patients with primary aldosteronism is associated with subsequent cardiorenal outcomes. The results also firstly point to the validity of the 2021 race-free CKD-EPI eGFR equation in healthcare and clinical decision-making.

Keywords: Cardiovascular risk; Cystatin C; Glomerular filtration rate; Hyperaldosteronism; Kidney failure.