Higher aldosterone is associated with increased renal impairment risk in patients with hypertension and abnormal glucose metabolism: a longitudinal study

OBJECTIVE: The aim of this study was to evaluate the association between plasma aldosterone concentration (PAC) and renal impairment in patients with both hypertension and abnormal glucose metabolism (AGM). METHODS: The longitudinal observational study included 2033 hypertensive individuals with AGM who did not have chronic kidney disease (CKD) at baseline. CKD was defined as estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m2 and/or positive proteinuria. Directed acyclic graphs and LASSO regression analyses were applied to identify adjusted sets. Cox proportional hazard models and linear regression were used to evaluate the association of PAC with CKD and its components including decreased renal function (DRF) and proteinuria. Mediation analysis was used to examine the role of blood pressure (BP) in the association between the two. RESULTS: During total follow-up of 5951 person-years with a median follow-up of 31 months, 291 participants developed CKD. The incidence of CKD was increased with the elevation in tertile PAC. Multivariable Cox model showed that PAC was positively associated with increased CKD risk (hazard ratio = 1.76 for natural log-transformed PAC, P < 0.001), and with increased risk of DRF and proteinuria. SBP mediated 7.5-17.9% of the association between PAC and renal impairment. Overall results remained consistent and significant in sensitivity analysis by excluding those with suspicious primary aldosteronism, too short follow-up time and mineralocorticoid receptor antagonists use. CONCLUSION: Higher PAC was associated with increased CKD risk in patients with hypertension and AGM, even in the absence of suspicious primary aldosteronism. The results indicate PAC may serve as a potential therapeutic target in this population.