Acute changes in glomerular filtration rate (GFR) can occur following initiation of interventions targeting progression of chronic kidney disease (CKD). These acute changes complicate the interpretation of long-term treatment effects. 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 following 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 meta-regression to assess the effect of intervention type, disease state, baseline GFR, and albuminuria on the magnitude of acute effects. The mean acute effect across all studies was -0.21 mL/min per 1.73m (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 1.73m). 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. 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.

Author