Supplementary Material for: Nephrotoxin Exposure in the 3 Years following Hospital Discharge Predicts Development or Worsening of Chronic Kidney Disease among Acute Kidney Injury Survivors

<b><i>Introduction:</i></b> Survivors of acute kidney injury (AKI) are at high risk of progression to chronic kidney disease (CKD), for which drugs may be a modifiable risk factor. <b><i>Methods:</i></b> We conducted a population-based cohort study of Olmsted County, MN residents who developed AKI while hospitalized between January 1, 2006, and December 31, 2014, using Rochester Epidemiology Project data. Adults with a hospitalization complicated by AKI who survived at least 90 days after AKI development were included. Medical records were queried for prescription of potentially nephrotoxic medications over the 3 years after discharge. The primary outcome was de novo or progressive CKD defined by either a new diagnosis code for CKD or ≥30% decline in estimated glomerular filtration rate from baseline. The composite of CKD, AKI readmission, or death was also evaluated. <b><i>Results:</i></b> Among 2,461 AKI survivors, 2,140 (87%) received a potentially nephrotoxic medication during the 3 years following discharge. When nephrotoxic medication use was analyzed in a time-dependent fashion, those actively prescribed at least one of these drugs experienced a significantly higher risk of de novo or progressive CKD (HR 1.38: 95% CI: 1.24, 1.54). Similarly, active potentially nephrotoxic medication use predicted a greater risk of the composite endpoint of CKD, AKI readmission, or death within 3 years of discharge (HR 1.41: 95% CI: 1.28, 1.56). <b><i>Conclusion:</i></b> In this population-based cohort study, AKI survivors actively prescribed one or more potentially nephrotoxic medications were at significantly greater risk for de novo or progressive CKD. An opportunity exists to reassess nephrotoxin appropriateness following an AKI episode to improve patient outcomes.

<b><i>引言：</i></b> 急性肾损伤（Acute Kidney Injury, AKI）幸存者进展为慢性肾脏病（Chronic Kidney Disease, CKD）的风险极高，而药物或为可改变的风险因素。<b><i>方法：</i></b> 本研究依托罗切斯特流行病学项目（Rochester Epidemiology Project）的数据，针对明尼苏达州奥姆斯特德县2006年1月1日至2014年12月31日期间住院期间发生AKI的居民开展基于人群的队列研究。纳入标准为：住院期间并发AKI且在AKI确诊后至少存活90天的成年患者。研究人员查阅了患者出院后3年内的医疗记录，以检索其潜在肾毒性药物的处方情况。本研究的主要结局为新发或进展性CKD，判定标准为：新增CKD诊断编码，或估算肾小球滤过率（estimated glomerular filtration rate, eGFR）较基线水平下降≥30%；同时还评估了复合结局：CKD、AKI再入院或死亡。<b><i>结果：</i></b> 本研究共纳入2461名AKI幸存者，其中2140例（87%）在出院后3年内使用了至少一种潜在肾毒性药物。当采用时间依赖性分析方式评估肾毒性药物使用情况时，当前使用至少一种此类药物的患者，其新发或进展性CKD的风险显著升高（风险比Hazard Ratio, HR=1.38，95%置信区间Confidence Interval, CI：1.24~1.54）。类似地，当前使用潜在肾毒性药物的患者，出院后3年内出现CKD、AKI再入院或死亡复合结局的风险同样显著升高（HR=1.41，95%CI：1.28~1.56）。<b><i>结论：</i></b> 本项基于人群的队列研究结果显示，当前使用一种或多种潜在肾毒性药物的AKI幸存者，其新发或进展性CKD的风险显著升高。临床可在AKI发作后重新评估肾毒性药物使用的合理性，以改善患者预后。