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

Rationale & ObjectiveThe 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 DesignSystematic review and meta-analysis of the SoC arms of RCTs analyzed as an observational study.Setting & Study PopulationsAdult patients with CKD enrolled in the SoC arm of RCTs.Selection Criteria for StudiesPhase 3 RCTs evaluating GFR decline as an outcome in SoC arms.Data ExtractionTwo independent reviewers evaluated RCTs for eligibility and extracted relevant data.Analytical ApproachThe 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.ResultsThe 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/1.73 m2 per year in the SoC arms with a high level of heterogeneity (I2, 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/1.73 m2 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.LimitationsDifferent methods assessing GFR in selected trials and observational design of the study.ConclusionsIn the last 3 decades, GFR decline has decreased over time in patients enrolled in RCTs who received the standard of care.Trial RegistrationRegistered at PROSPERO with record number CRD42022357704.Plain-Language SummaryThis 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. 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. 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/1.73 m2 per year in the SoC arms with a high level of heterogeneity (I2, 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/1.73 m2 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.