GFR Decline and Subsequent Risk of Established Kidney Outcomes: A Meta-analysis of 37 Randomized Controlled Trials
GFR Decline and Subsequent Risk of Established Kidney Outcomes: A Meta-analysis of 37 Randomized Controlled Trials
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DOI：
10.1053/j.ajkd.2014.08.018
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发表时间：
2014-12-01
影响因子：
13.2
通讯作者：
Inker, Lesley A.
中科院分区：
文献类型：
--
作者：
Heerspink, Hiddo J. Lambers;Tighiouart, Hocine;Inker, Lesley A.
背景资料：目前确定的慢性肾脏疾病（CKD）进展临床试验终点是终末期肾脏疾病和血清肌酐水平加倍，估计肾小球滤过率（eGFR）下降约57%。在临床试验中使用替代终点来缩短试验持续时间和减少样本量的兴趣越来越大。作为使用较小的GFR下降作为替代终点的评估的一部分，我们检查了不同水平的eGFR下降与随后建立的终点的发展的相关性，并评估了不同肾脏疾病临床表现和干预措施中eGFR下降水平的一致性。研究设计：随机对照试验的观察分析。9，488名参与者参加了37项CKD随机对照试验。预测因子：替代终点，定义为eGFR从基线至第12个月下降30%和40%。通过基线eGFR、蛋白尿、病因和干预措施对效应进行修正。结局：确定的终点，定义为终末期肾病，eGFR < 15 mL/min/1.73 m2，或血清肌酐水平加倍。结果：从基线到12个月，分别有16.1%和7.8%的参与者eGFR下降>= 30%或>= 40%。在12个月基线期后的中位随访2.0（IQR，1.2-3.1）年中，观察到2，661个已确定的终点。在eGFR下降和随后确定的终点之间观察到强线性相关。eGFR下降30%和40%与下降0%相比，确定终点的HR分别为9.6（95% CI，7.3-12.6）和20.3（95% CI，14.1-29.3）。无论基线eGFR、蛋白尿、疾病原因和干预措施如何，这种关联都是一致的。局限性：观察性研究受残余混杂因素的影响。eGFR下降幅度较小与随后确定的终点之间的强相关性在肾脏疾病和干预的不同临床特征中一致，并支持在CKD进展的临床试验中实施替代终点。(C)2014年，美国国家肾脏基金会（National Kidney Foundation，Inc.）
Background: The currently established end points for clinical trials of progression of chronic kidney disease (CKD) are end-stage renal disease and doubling of serum creatinine level, which approximates a 57% decline in estimated glomerular filtration rate (eGFR). There is increased interest in using alternative end points in clinical trials to shorten trial duration and reduce sample size. As part of an evaluation of using lesser declines in GFR as alternative end points, we examined the associations of various levels of eGFR decline with the subsequent development of established end points and assess the consistency of alternate levels of eGFR decline across varying clinical manifestations of kidney disease and interventions.Study Design: Observational analysis of randomized controlled trials.Setting & Participants: 9,488 participants in 37 randomized controlled trials in CKD.Predictor: Alternative end points, defined as 30% and 40% declines in eGFR from baseline to month 12. Effect modification by baseline eGFR, proteinuria, cause of disease, and interventions.Outcomes: Established end point, defined as end-stage renal disease, eGFR < 15 mL/min/1.73 m(2), or doubling of serum creatinine level.Results: From baseline to 12 months, 16.1% and 7.8% of participants had eGFR declines of >= 30% or >= 40%, respectively. Over a median follow-up of 2.0 (IQR, 1.2-3.1) years after the 12-month baseline period, 2,661 established end points were observed. A strong linear association was observed between eGFR decline and subsequent established end points. HRs for the established end point for 30% and 40% decreases in eGFR compared to a 0% decline were 9.6 (95% CI, 7.3-12.6) and 20.3 (95% CI, 14.1-29.3), respectively. The associations were consistent regardless of baseline eGFR, proteinuria, causes of disease, and interventions.Limitations: Observational study subject to residual confounding.Conclusions: The strong associations between lesser declines in eGFR and the subsequent development of established end points were consistent across different clinical characteristics of kidney disease and interventions and support implementation of alternative end points in clinical trials of CKD progression. (C) 2014 by the National Kidney Foundation, Inc.