Early versus Delayed Initiation of Renal Replacement Therapy in Critically Ill Patients with Acute Kidney Injury: A Systematic Review and Meta-Analysis of Randomized Trials

IntroductionAcute kidney injury (AKI) affects up to 66% of critically ill patients and is associated with substantial morbidity and mortality. Renal replacement therapy (RRT) remains the cornerstone of management in severe AKI, yet the optimal timing of initiation remains controversial. While early RRT may rapidly correct metabolic derangements, it may expose patients to unnecessary risks. We performed an updated systematic review and meta-analysis to evaluate the effects of early versus delayed RRT initiation on mortality and adverse outcomes in critically ill patients with AKI. MethodsWe systematically searched PubMed, Embase, Cochrane CENTRAL, and Web of Science up to August 2025 for randomized controlled trials (RCTs) comparing early versus delayed RRT initiation in adult ICU patients with AKI. Two reviewers independently screened studies, extracted data, and assessed risk of bias using RoB 2.0. Pooled analyses were conducted using a random-effects model. Subgroup analyses were performed by age (<65 vs [&ge;]65 years) and illness severity (SOFA <12 vs [&ge;]12). Quality of evidence was graded using GRADE. ResultsA total of 19 RCTs comprising 12,162 patients were included. Of these, 5,450 patients were randomized to early RRT and 5,452 to delayed RRT. The mean initiation time was 10.5 hours in early groups versus 35.3 hours in delayed groups. Overall, early initiation did not significantly reduce 30-day mortality (RR = 0.96, 95% CI: 0.89-1.04; p = 0.31) or 90-day mortality (RR = 0.90, 95% CI: 0.76-1.06; p = 0.17). Subgroup analyses showed no survival benefit across age (<65 vs [&ge;]65) or SOFA (<12 vs [&ge;]12) strata. Adverse events analysis revealed that early initiation was associated with a higher risk of infection (RR = 1.21, 95% CI: 1.03-1.39; p = 0.02), while no significant differences were found in hypotension (RR = 1.03, 95% CI: 0.81-1.25), arrhythmias (RR = 1.10, 95% CI: 0.78-1.42), or bleeding events (RR = 0.93, 95% CI: 0.75-1.11). ConclusionEarly initiation of RRT in critically ill patients with AKI does not improve short- or long-term mortality and is associated with an increased risk of infection. These findings support a delayed strategy, reserving RRT for patients with absolute indications or those not improving with conservative management. Individualized decision-making based on clinical status and illness trajectory should remain the standard of care.