GFR Decline as an Alternative End Point to Kidney Failure in Clinical Trials: A Meta-analysis of Treatment Effects From 37 Randomized Trials
GFR Decline as an Alternative End Point to Kidney Failure in Clinical Trials: A Meta-analysis of Treatment Effects From 37 Randomized Trials
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DOI：
10.1053/j.ajkd.2014.08.017
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发表时间：
2014-12-01
影响因子：
13.2
通讯作者：
Levey, Andrew S.
中科院分区：
文献类型：
--
作者：
Inker, Lesley A.;Heerspink, Hiddo J. Lambers;Levey, Andrew S.
背景：在肾脏疾病进展试验中使用替代终点的兴趣越来越大。目前确定的终末期肾病和血清肌酐水平加倍（相当于估计肾小球滤过率（eGFR）下降57%）的终点是慢性肾病（CKD）的晚期事件，需要长期随访的大型临床试验。作为全面评估eGFR下降幅度较小作为替代终点的一部分，我们描述了干预措施对替代终点和过去试验中既定终点的治疗效果的一致性。研究设计：诊断测试研究。设置和人群：来自37项随机对照试验的9，488名参与者5种干预类型的慢性肾病进展。指数测试：替代终点包括整个研究期间以及至12、18和24个月eGFR较基线的百分比变化（20%、30%、40%和57%）。在下次访视时确认与未确认的eGFR变化。参考试验：历史上确定的至治疗肾衰竭复合终点的时间（终末期肾病）、未经治疗的肾衰竭（GFR < 15 mL/min/1.73 m（2）），或在整个研究期间血清肌酐水平加倍。在中位数为3.62年的随访中，有3，070个确定的终点。与确定的终点相比，eGFR下降幅度较小与较大以及随访间隔较长与较短的替代终点数量更多。总的趋势是治疗效果减弱，终点定义为eGFR下降较小，未确认终点的衰减更大，但低蛋白饮食干预除外，观察到更强的治疗效果。之比5种干预类型的替代终点的HR（95%可信区间）范围为0.91（0.64-1.43）至1.12（0.89-1.40）下降40%，从0.88（0.63-1.39）至1.15（0.88-1.54）在整个研究期间下降30%，表明治疗效果的一致性。局限性：有限的各种干预措施测试和低统计功率为许多CKD clinical trials.Conclusions：这些结果提供了一些支持使用较小的eGFR下降作为替代终点，与40%比30%下降更强的支持。(C)2014年，美国国家肾脏基金会（National Kidney Foundation，Inc.）
Background: There is increased interest in using alternative end points for trials of kidney disease progression. The currently established end points of end-stage renal disease and doubling of serum creatinine level, equivalent to a 57% decline in estimated glomerular filtration rate (eGFR), are late events in chronic kidney disease (CKD), requiring large clinical trials with long follow-up. As part of a comprehensive evaluation of lesser declines in eGFR as alternative end points, we describe the consistency of treatment effects of intervention on the alternative and established end points in past trials.Study Design: Diagnostic test study.Setting & Population: 9,488 participants from 37 randomized controlled trials of CKD progression across 5 intervention types.Index Test: Alternative end points including percentage change in eGFR from baseline (20%, 30%, 40%, and 57%) throughout study duration and to 12, 18, and 24 months. eGFR change confirmed versus nonconfirmed at the next visit.Reference Test: The historically established end point of time to composite of treated kidney failure (end-stage renal disease), untreated kidney failure (GFR < 15 mL/min/1.73 m(2)), or doubling of serum creatinine level throughout study duration.Results: Over a median of 3.62 years' follow-up, there were 3,070 established end points. Compared to the established end point, the number of alternative end points was greater for smaller versus larger declines in eGFR and longer versus shorter follow-up intervals. There was a general trend toward attenuation of the treatment effect with end points defined by a lesser eGFR decline, with greater attenuation with nonconfirmed end points, except for the low-protein-diet intervention, for which a stronger treatment effect was observed. The ratio (95% credible interval) of the HR for the alternative to established end point for the 5 intervention types ranged from 0.91 (0.64-1.43) to 1.12 (0.89-1.40) for 40% decline and from 0.88 (0.63-1.39) to 1.15 (0.88-1.54) for 30% decline for the overall study duration, indicating consistency of treatment effects.Limitations: Limited variety of interventions tested and low statistical power for many CKD clinical trials.Conclusions: These results provide some support for the use of lesser eGFR declines as a surrogate end point, with stronger support for the 40% than 30% decline. (C) 2014 by the National Kidney Foundation, Inc.