Effectiveness of Renal Replacement Therapy in Severe Acute Kidney Injury: A Systematic Review of Randomized Controlled Trials

Abstract

Introduction: Severe acute kidney injury (AKI) affects a substantial proportion of critically ill adults, with mortality approaching 50% once renal replacement therapy (RRT) becomes necessary. Four core prescriptive decisions—timing of initiation, intensity of clearance, modality selection, and anticoagulation strategy—remain contested. This systematic review aimed to determine whether any specific RRT strategy improves survival, kidney recovery, circuit performance, and safety in adults with severe AKI across all four domains.

Methods: The study strictly adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines from inception to 30 April 2026 for randomized controlled trials (RCTs) enrolling adults with severe AKI (KDIGO stage 2–3 or equivalent) comparing RRT strategies. Two reviewers independently screened records, extracted data, and appraised risk of bias using Cochrane RoB 2; certainty was rated with GRADE. Fifteen outcome domains were pre-specified. Evidence was synthesised within domain using structured narrative synthesis with effect-direction tabulation.

Results: Twenty-nine RCTs enrolling 12,129 participants were included (9 timing trials, 8 dose/intensity trials, 7 modality trials, and 5 anticoagulation trials). Overall risk of bias was low in 8 trials, of some concern in 19, and high in 2. No RRT strategy reduced all-cause mortality: 90-day mortality was 43.9% versus 43.7% for accelerated versus standard initiation (RR 1.00, 95% CI 0.93–1.09; P=0.92) and 44.7% in both arms of higher- versus lower-intensity continuous RRT (OR 1.00, 95% CI 0.81–1.23; P=0.99). Accelerated initiation significantly increased RRT dependence among 90-day survivors (10.4% vs 6.0%; RR 1.74, 95% CI 1.24–2.43) and adverse events (23.0% vs 16.5%; P<0.001); excessive postponement was significantly harmful (adjusted HR for 60-day death 1.65, 95% CI 1.09–2.50; P=0.018). A delayed strategy spared RRT entirely in 38–49% of patients. Regional citrate anticoagulation significantly prolonged filter life span (47 vs 26 h; difference 15 h, 95% CI 11–20; P<0.001) and halved bleeding complications (5.1% vs 16.9%; P<0.001). Higher-intensity clearance significantly increased hypophosphataemia (65% vs 54%; P<0.001) and prolonged mechanical ventilation (HR for extubation 0.67, 95% CI 0.52–0.88). Sustained low-efficiency dialysis significantly reduced ventilator days, ICU days, transfusion volume, and nursing cost versus continuous haemofiltration.

Discussion: The consistent null effect on mortality across 12,129 randomised patients, with an individual-patient-data meta-analysis showing no heterogeneity, indicates that survival in severe AKI is governed by underlying critical illness rather than extracorporeal prescription once a threshold of adequacy is reached. Therapeutic gains are therefore not in survival but in avoidance of unnecessary therapy, protection of kidney recovery, circuit longevity, bleeding avoidance, and resource preservation—outcomes on which the evidence is statistically significant, internally consistent, and directly actionable.

Conclusion: In adults with severe AKI, no timing, dose, or modality strategy improves survival. A watchful-waiting strategy with strictly defined mandatory triggers, a delivered continuous effluent dose of 20–25 mL/kg/h (or thrice-weekly intermittent haemodialysis with Kt/V 1.2–1.4), modality selection driven by haemodynamics and local resources, and regional citrate as the default anticoagulant constitute the evidence-based standard. Postponement must not, however, be indefinite.