Supplementary Material for: Relationship between cumulative exposure and time course of plasma aldosterone concentrations and chronic kidney disease in hypertensive patients: a real-world cohort study

Objective: This study aimed to investigate the effects of cumulative exposure to plasma aldosterone concentration (PAC) and its time course on chronic kidney disease (CKD) in hypertensive patients, with the goal of providing insights for preventing future CKD events, especially in younger hypertensive patients.
Methods: This study enrolled a total of 7142 hypertensive participants, each of whom had undergone at least two PAC measurements before the age of 60. We calculated annual PAC area under the curve (AUC) and used Cox regression analyses to examine the association between annual PAC_AUC and CKD risk. We also explored how the timing course of PAC accumulation affected CKD risk, as different stages of PAC accumulation, even with the same annual PAC_AUC, may lead to varying risks. Additionally, we conducted a comparative analysis to assess the predictive performance of annual PAC_AUC versus single PAC measurements.
Results: During a median follow-up of 5.83 years, 754 participants developed CKD. The results showed a progressive increase in CKD risk with higher annual PAC_AUC [hazard ratio: 1.19; 95% confidence interval: 1.17, 1.21]. Moreover, the timing course of PAC accumulation modulates this risk; Kaplan-Meier curves indicated that participants with similar annual PAC_AUC but earlier PAC exposure had a higher CKD risk compared to those exposed later (Log-rank test, p < 0.001). Furthermore, annual PAC_AUC outperformed single PAC measurements in predictive accuracy.
Conclusion: CKD risk is influenced by both annual PAC_AUC and the timie course of PAC exposure. Participants exposed to elevated PAC earlier had a higher CKD risk than those exposed later, even at the same annual PAC_AUC. This highlights the importance of early PAC control to prevent CKD.