Find Paper, Faster
Example:10.1021/acsami.1c06204 or Chem. Rev., 2007, 107, 2411-2502
Acute Treatment Effects on GFR in Randomized Clinical Trials of Kidney Disease Progression
Journal of the American Society of Nephrology  (IF10.121),  Pub Date : 2022-02-01, DOI: 10.1681/asn.2021070948
Brendon L. Neuen, Hocine Tighiouart, Hiddo J.L. Heerspink, Edward F. Vonesh, Juhi Chaudhari, Shiyuan Miao, Tak Mao Chan, Fernando C. Fervenza, Jürgen Floege, Marian Goicoechea, William G. Herrington, Enyu Imai, Tazeen H. Jafar, Julia B. Lewis, Philip Kam-Tao Li, Francesco Locatelli, Bart D. Maes, Ronald D. Perrone, Manuel Praga, Annalisa Perna, Francesco P. Schena, Christoph Wanner, Jack F.M. Wetzels, Mark Woodward, Di Xie, Tom Greene, Lesley A. Inker, on behalf of CKD-EPI Clinical Trials

Background

Acute changes in GFR can occur after initiation of interventions targeting progression of CKD. These acute changes complicate the interpretation of long-term treatment effects.

Methods

To assess the magnitude and consistency of acute effects in randomized clinical trials and explore factors that might affect them, we performed a meta-analysis of 53 randomized clinical trials for CKD progression, enrolling 56,413 participants with at least one estimated GFR measurement by 6 months after randomization. We defined acute treatment effects as the mean difference in GFR slope from baseline to 3 months between randomized groups. We performed univariable and multivariable metaregression to assess the effect of intervention type, disease state, baseline GFR, and albuminuria on the magnitude of acute effects.

Results

The mean acute effect across all studies was –0.21 ml/min per 1.73 m2 (95% confidence interval, –0.63 to 0.22) over 3 months, with substantial heterogeneity across interventions (95% coverage interval across studies, –2.50 to +2.08 ml/min per 1.73 m2). We observed negative average acute effects in renin angiotensin system blockade, BP lowering, and sodium-glucose cotransporter 2 inhibitor trials, and positive acute effects in trials of immunosuppressive agents. Larger negative acute effects were observed in trials with a higher mean baseline GFR.

Conclusion

The magnitude and consistency of acute GFR effects vary across different interventions, and are larger at higher baseline GFR. Understanding the nature and magnitude of acute effects can help inform the optimal design of randomized clinical trials evaluating disease progression in CKD.