Evaluation of Variation in the Performance of GFR Slope as a Surrogate End Point for Kidney Failure in Clinical Trials that Differ by Severity of CKD. Issue 2 (19th February 2023)

• Record Type: Journal Article
• Authors: Collier, Willem; Inker, Lesley A.; Haaland, Benjamin; Appel, Gerald B.; Badve, Sunil V.; Caravaca-Fontán, Fernando; Chalmers, John; Floege, Jürgen; Goicoechea, Marian; Imai, Enyu; Jafar, Tazeen H.; Lewis, Julia B.; Li, Philip K.T.; Locatelli, Francesco; Maes, Bart D.; Neuen, Brendon L.; Perrone, Ronald D.; Remuzzi, Giuseppe; Schena, Francesco P.; Wanner, Christoph; Heerspink, Hiddo J.L.; Greene, Tom
• Is Part Of: Clinical journal of the American Society of Nephrology. Volume 18:Issue 2(2023)
• Page Start: 183
• Page End: 192
• Publication Date: 2023-02-19
• Subjects: GFR slope -- meta-analysis -- effect modifier -- biomarkers -- chronic kidney disease -- surrogate end point
• DOI: 10.2215/CJN.0000000000000050
• Languages: English
• ISSNs: 1555-9041

Abstract

Visual Abstract: Abstract : Background: The GFR slope has been evaluated as a surrogate end point for kidney failure in meta-analyses on a broad collection of randomized controlled trials (RCTs) in CKD. These analyses evaluate how accurately a treatment effect on GFR slope predicts a treatment effect on kidney failure. We sought to determine whether severity of CKD in the patient population modifies the performance of GFR slope. Methods: We performed Bayesian meta-regression analyses on 66 CKD RCTs to evaluate associations between effects on GFR slope (the chronic slope and the total slope over 3 years, expressed as mean differences in ml/min per 1.73 m 2 /yr) and those of the clinical end point (doubling of serum creatinine, GFR <15 ml/min per 1.73 m 2, or kidney failure, expressed as a log-hazard ratio), where models allow interaction with variables defining disease severity. We evaluated three measures (baseline GFR in 10 ml/min per 1.73 m 2, baseline urine albumin-to-creatinine ratio [UACR] per doubling in mg/g, and CKD progression rate defined as the control arm chronic slope, in ml/min per 1.73 m 2 /yr) and defined strong evidence for modification when 95% posterior credible intervals for interaction terms excluded zero. Results: There was no evidence for modification by disease severity when evaluating 3-year total slope (95% credible intervals for the interaction slope: baseline GFR [−0.05 to 0.03]; baseline UACR [−0.02 to 0.04]; CKD progression rate [−0.07 to 0.02]). There was strong evidence for modification in evaluations of chronic slope (95% credible intervals: baseline GFR [0.02 to 0.11]; baseline UACR [−0.11 to −0.02]; CKD progression rate [0.01 to 0.15]). Conclusions: These analyses indicate consistency of the performance of total slope over 3 years, which provides further evidence for its validity as a surrogate end point in RCTs representing varied CKD populations.