Effectiveness of Multicomponent Interventions in Slowing Progression of Chronic Kidney Disease Stages G3-G4: A Systematic Review and Meta-Analysis

Background: Various multicomponent interventions (MCIs) have been increasingly used for managing patients with chronic kidney disease (CKD) G3-G4, but they have not been systematically evaluated for the collective evidence of their effectiveness. Hence, we conducted this systematic review and meta-analysis to evaluate the effectiveness of MCIs in delaying CKD progression and improving health outcomes in patients with CKD G3-G4. Methods: We completed a systematic literature search in PubMed, Embase, CENTRAL, Web of Science, and CINAHL from inception to July 30, 2025. We included randomized controlled trials (RCTs) studying the effectiveness of MCIs lasting at least six months among patients with CKD G3-G4. We used random-effects meta-analyses to estimate the effectiveness of MCIs on the primary outcome, estimated glomerular filtration rate (eGFR), and secondary outcomes, including other kidney function indicators, CKD risk factors, and adverse events. Results: Nineteen RCTs (36,296 patients with CKD G3-G4; median follow-up of 24 months) were included. Components of MCI included a mix of behavioral modifications, guideline-directed medical therapy, enabling technology components, and team-based care. Compared to control, MCIs were associated with small improvements in eGFR (Mean difference (MD) = 1.18 mL/min/1.73 m 2 ; 95% confidence interval (CI), 0.09-2.27; 19 trials, low certainty of evidence), eGFR slope (MD=0.61 mL/min/1.73 m 2 /year; 95% CI, 0.16-1.06; six trials, moderate certainty of evidence), and a moderate reduction in HbA1c (MD = -0.26; 95% CI, -0.49 to -0.02; nine trials, low certainty of evidence). No statistically significant effects were observed for albuminuria, blood pressure, or adverse events. Conclusions: Our findings suggest the potential role of MCIs in delaying CKD progression and improving glycemic control among patients with CKD G3-G4. Nonetheless, the certainty of evidence is low for eGFR and HbA1c and moderate for eGFR slope, suggesting overall modest clinical relevance. High-quality studies are needed to confirm the effectiveness, cost-effectiveness, and scalability of MCIs for this high-risk patient group.