Division of Nephrology, University of Campania "Luigi Vanvitelli," Naples, Italy.
Division of Nephrology, University of Campania "Luigi Vanvitelli," Naples, Italy.
Am J Kidney Dis. 2024 Apr;83(4):435-444.e1. doi: 10.1053/j.ajkd.2023.09.014. Epub 2023 Nov 11.
RATIONALE & OBJECTIVE: The standard of care (SoC) group of randomized controlled trials (RCTs) is a useful setting to explore the secular trends in kidney disease progression because implementation of best clinical practices is pursued for all patients enrolled in trials. This meta-analysis evaluated the secular trend in the change of glomerular filtration rate (GFR) decline in the SoC arm of RCTs in chronic kidney disease (CKD) published in the last 30 years.
Systematic review and meta-analysis of the SoC arms of RCTs analyzed as an observational study.
SETTING & STUDY POPULATIONS: Adult patients with CKD enrolled in the SoC arm of RCTs.
Phase 3 RCTs evaluating GFR decline as an outcome in SoC arms.
Two independent reviewers evaluated RCTs for eligibility and extracted relevant data.
The mean of GFR declines extracted in the SoC arm of selected RCTs were pooled by using a random effects model. Meta-regression analyses were performed to identify factors that may explain heterogeneity.
The SoC arms from 92 RCTs were included in the meta-analysis with a total of 32,202 patients. The overall mean GFR decline was-4.00 (95% CI, -4.55 to-3.44) mL/min/1.73m per year in the SoC arms with a high level of heterogeneity (I, 98.4% [95% CI, 98.2-98.5], P<0.001). Meta-regression analysis showed an association between publication year (β estimate, 0.09 [95% CI, 0.032-0.148], P=0.003) and reduction in GFR over time. When evaluating publication decade categorically, GFR decline was-5.44 (95% CI, -7.15 to-3.73), -3.92 (95% CI, -4.82 to-3.02), and -3.20 (95% CI, -3.75 to -2.64) mL/min/1.73m per year during 1991-2000, 2001-2010, and 2011-2023, respectively. Using meta-regression, the heterogeneity of GFR decline was mainly explained by age and proteinuria.
Different methods assessing GFR in selected trials and observational design of the study.
In the last 3 decades, GFR decline has decreased over time in patients enrolled in RCTs who received the standard of care.
Registered at PROSPERO with record number CRD42022357704.
PLAIN-LANGUAGE SUMMARY: This study evaluated the secular trend in the change in glomerular filtration rate (GFR) decline in the placebo arms of randomized controlled trials (RCTs) that were studying approaches to protect the kidneys in the setting of chronic kidney disease. The placebo groups of RCTs are useful for examining whether the rate of progression of kidney disease has changed over time. We found an improvement in the slope of change in GFR over time. These findings suggest that adherence to standards of kidney care as implemented in clinical trials may be associated with improved clinical outcomes, and these data may inform the design of future RCTs in nephrology.
标准治疗（SoC）组的随机对照试验（RCT）是探索肾脏病进展的时间趋势的有用环境，因为所有入组试验的患者都在追求最佳临床实践的实施。本荟萃分析评估了过去 30 年发表的慢性肾脏病（CKD）SoC 臂 RCT 中肾小球滤过率（GFR）下降变化的时间趋势。
作为观察性研究对 RCT 的 SoC 臂进行系统评价和荟萃分析。
CKD 入组 SoC 臂 RCT 的成年患者。
评估 SoC 臂 GFR 下降的 3 期 RCT。
两名独立审查员评估 RCT 的入选标准并提取相关数据。
使用随机效应模型对选定 RCT 的 SoC 臂中提取的 GFR 下降平均值进行汇总。进行了荟萃回归分析以确定可能解释异质性的因素。
该荟萃分析纳入了 92 项 RCT 的 SoC 臂，共有 32,202 名患者。SoC 臂的总体平均 GFR 下降为-4.00（95%CI，-4.55 至-3.44）mL/min/1.73m/年，异质性水平很高（I，98.4% [95%CI，98.2-98.5]，P<0.001）。荟萃回归分析显示，发表年份（β估计值，0.09 [95%CI，0.032-0.148]，P=0.003）与随时间推移的 GFR 降低之间存在关联。当按出版十年进行分类评估时，GFR 下降分别为-5.44（95%CI，-7.15 至-3.73）、-3.92（95%CI，-4.82 至-3.02）和-3.20（95%CI，-3.75 至-2.64）mL/min/1.73m/年。使用荟萃回归，GFR 下降的异质性主要由年龄和蛋白尿解释。
选定试验中评估 GFR 的方法不同，以及研究的观察性设计。
在过去的 30 年中，接受标准治疗的入组 RCT 患者的 GFR 下降随时间呈下降趋势。
在 PROSPERO 注册，记录号 CRD42022357704。
本研究评估了在慢性肾脏病（CKD）的背景下，研究保护肾脏方法的随机对照试验（RCT）中安慰剂组的肾小球滤过率（GFR）下降变化的时间趋势。RCT 的安慰剂组可用于检查肾病的进展速度是否随时间而变化。我们发现 GFR 变化斜率随时间的改善。这些发现表明，临床试验中实施的肾脏护理标准的坚持可能与改善临床结果有关，这些数据可能为肾脏病学未来的 RCT 设计提供信息。
