Secular Trend in GFR Decline in Non-Dialysis CKD Based on Observational Data From Standard of Care Arms of Trials

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. Study design: 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. Selection criteria for studies: Phase 3 RCTs evaluating GFR decline as an outcome in SoC arms. Data extraction: Two independent reviewers evaluated RCTs for eligibility and extracted relevant data. Analytical approach: 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. Results: 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(2) per year in the SoC arms with a high level of heterogeneity (I-2, 98.4% [95% CI, 98.2-98.5], P<0.001). Meta-regression analysis showed an association between publication year (beta 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(2) 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. Limitations: Different methods assessing GFR in selected trials and observational design of the study. Conclusions: In the last 3 decades, GFR decline has decreased over time in patients enrolled in RCTs who received the standard of care.