Supplementary Material for: Age-Dependent Effects of Acute Kidney Injury on End-Stage Kidney Disease and Mortality in Patients with Moderate to Severe Chronic Kidney Disease

<b><i>Introduction:</i></b> Old age has been considered as a positive modifier of chronic kidney disease (CKD), but the progression of CKD is often accelerated by acute kidney injury (AKI) in older adults. This study aimed to investigate this paradoxical interplay and identify age-specific predictors of end-stage kidney disease (ESKD). <b><i>Methods:</i></b> This retrospective cohort included 6,101 patients with CKD stage 3B-5 followed at a single center during 2005–2018. Participants were stratified into four age groups to explore age-dependent influences on the risk of ESKD and all-cause mortality. Multivariate Cox proportional hazard regression model with competing risk analysis was used to identify predictors of outcomes. <b><i>Results:</i></b> During a median follow-up of 2.68 years, 1,650 (27.0%) patients developed ESKD and 541 (8.9%) patients died. The rate of ESKD decreased with advancing age, being lowest in the very old-aged (&gt;75 years) group who displayed the slowest rate of estimated glomerular filtration rate (eGFR) decline. Multivariate Cox proportional hazard regression adjusted for competing death showed that younger ages, compared with patients aged &gt;75 years, together with AKI episodes and several traditional risk factors were identified as predictors for ESKD. The impact of AKI episodes on ESKD development was most prominent in patients aged &gt;75 years. These results were confirmed with subgroup analyses in patients with outcomes of different ages. <b><i>Conclusion:</i></b> Older adults with CKD exhibited a slower decline rate of eGFR, yet they were more likely to develop ESKD following AKI episodes. These results suggest tackling AKI is needed to prevent accelerated initiation of renal replacement therapy in elderly patients with pre-existing CKD.

**<i>引言：</i>** 老年曾被认为是慢性肾脏病（CKD）的正向调节因素，但老年群体的慢性肾脏病进展常因急性肾损伤（AKI）而加快。本研究旨在探究这一相悖的交互关系，并明确终末期肾脏病（ESKD）的年龄特异性预测因素。**<i>方法：</i>** 本回顾性队列研究纳入2005年至2018年间在单中心随访的6101例CKD 3B-5期患者。将研究对象按年龄分层分为四组，以探究年龄对ESKD发病风险及全因死亡率的年龄依赖性影响。采用整合竞争风险分析的多因素Cox比例风险回归模型，以明确研究结局的预测因素。**<i>结果：</i>** 中位随访2.68年期间，共有1650例（27.0%）患者进展为ESKD，541例（8.9%）患者死亡。ESKD的发生率随年龄增长呈下降趋势，在≥75岁的极老年组中发生率最低，该组的估算肾小球滤过率（eGFR）下降速率也最为缓慢。经竞争死亡风险校正的多因素Cox比例风险回归分析显示，与≥75岁患者相比，更年轻的年龄、急性肾损伤发作史及多项传统危险因素均为ESKD的独立预测因素。其中，急性肾损伤发作对ESKD发生的影响在≥75岁患者中最为显著。针对不同年龄亚组的分析进一步验证了上述研究结果。**<i>结论：</i>** 合并慢性肾脏病的老年群体虽估算肾小球滤过率下降速率更慢，但在发生急性肾损伤后进展为终末期肾脏病的风险更高。本研究结果提示，对于已罹患慢性肾脏病的老年患者，需积极干预急性肾损伤，以延缓肾脏替代治疗的启动时机。