肾素-血管紧张素系统抑制期间估算肾小球滤过率急性下降与不良结局风险之间的关联
Association between Acute Declines in eGFR during Renin-Angiotensin System Inhibition and Risk of Adverse Outcomes.
作者信息
Ku Elaine, Tighiouart Hocine, McCulloch Charles E, Inker Lesley A, Adingwupu Ogechi M, Greene Tom, Estacio Raymond O, Woodward Mark, de Zeeuw Dick, Lewis Julia B, Hannedouche Thierry, Hou Fan Fan, Jafar Tazeen H, Imai Enyu, Remuzzi Giuseppe, Heerspink Hiddo J L, Toto Robert D, Sarnak Mark J
机构信息
Division of Nephrology, Departments of Medicine and Pediatrics, University of California San Francisco, San Francisco, California.
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
出版信息
J Am Soc Nephrol. 2024 Oct 1;35(10):1402-1411. doi: 10.1681/ASN.0000000000000426. Epub 2024 Jun 18.
KEY POINTS
Renin-angiotensin system inhibition was favorable for risk of kidney failure (compared with 0% decline with use of placebo or other agents) up to declines in eGFR of 13% over a 3-month period. Relation between eGFR decline after renin-angiotensin system inhibitor initiation and risk of outcomes was stronger in the first 2 years of follow-up and waned over time.
BACKGROUND
Declines in GFR occur commonly when renin-angiotensin system (RAS) inhibitors are started. Our objective was to determine the relation between declines in eGFR during trials of RAS inhibition and kidney outcomes.
METHODS
We included participants with CKD (eGFR <60 ml/min per 1.73 m) from 17 trials of RAS inhibition. The exposure was subacute declines in eGFR expressed as % change between randomization and month 3, and in the subset of trials with data available, we also examined % change in eGFR between randomization and month 1. The primary outcome was kidney failure with replacement therapy. Cox proportional hazards models were used to examine the association between subacute declines in eGFR and risk of kidney failure. We used spline models to identify the threshold of change in eGFR below which RAS inhibition was favorable (conservatively comparing a given decline in eGFR with RAS inhibition to no decline in the comparator).
RESULTS
A total of 11,800 individuals with mean eGFR 43 (SD 11) ml/min per 1.73 m and median urine albumin-to-creatinine ratio of 362 mg/g (interquartile range, 50–1367) were included, and 1162 (10%) developed kidney failure. The threshold of decline in eGFR that favored the use of RAS inhibitors for kidney failure was estimated to be up to 13% (95% confidence interval, 8% to 17%) over a 3-month interval and up to 21% (95% confidence interval, 15% to 27%) over a 1-month interval after starting RAS inhibitors.
CONCLUSIONS
In patients treated with RAS inhibitors, ≤13% decline in eGFR over a 3-month period or ≤21% decline over a 1-month period was associated with lower risk of kidney failure compared with no decline in those assigned to placebo or other agents.
关键点
在长达3个月的时间内，肾素-血管紧张素系统抑制对肾衰竭风险有益（与使用安慰剂或其他药物时0%的下降率相比），估算肾小球滤过率（eGFR）下降幅度可达13%。在随访的前2年中，肾素-血管紧张素系统抑制剂开始使用后eGFR下降与预后风险之间的关系更强，且随着时间推移而减弱。
背景
开始使用肾素-血管紧张素系统（RAS）抑制剂时，肾小球滤过率（GFR）通常会下降。我们的目标是确定RAS抑制试验期间eGFR下降与肾脏预后之间的关系。
方法
我们纳入了17项RAS抑制试验中慢性肾脏病（eGFR<60 ml/min/1.73m²）的参与者。暴露因素为eGFR的亚急性下降，以随机分组至第3个月之间的百分比变化表示，在有可用数据的试验子集中，我们还检查了随机分组至第1个月之间eGFR的百分比变化。主要结局是需要肾脏替代治疗的肾衰竭。采用Cox比例风险模型来检验eGFR亚急性下降与肾衰竭风险之间的关联。我们使用样条模型来确定eGFR变化的阈值，低于该阈值时RAS抑制是有益的（保守地将RAS抑制时eGFR的给定下降与对照中无下降进行比较）。
结果
共纳入11800例个体，平均eGFR为43（标准差11）ml/min/1.73m²，尿白蛋白与肌酐比值中位数为362mg/g（四分位间距，50-1367），其中1162例（10%）发生肾衰竭。在开始使用RAS抑制剂后的3个月间隔内，有利于使用RAS抑制剂治疗肾衰竭的eGFR下降阈值估计高达13%（95%置信区间，8%至17%），1个月间隔内高达21%（95%置信区间，15%至27%）。
结论
在接受RAS抑制剂治疗的患者中，与分配至安慰剂或其他药物组且eGFR无下降的患者相比，3个月内eGFR下降≤13%或1个月内下降≤21%与较低的肾衰竭风险相关。
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