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Objectives: The objective of this study is to compare early versus late/standard initiation of renal replacement therapy (RRT) in patients with acute kidney injury (AKI). Data Sources: MEDLINE/PubMed, Embase, Google Scholar, Cochrane Central Register of Controlled Trials, and the Cochrane renal group till August 15, 2020. Study Selection: Randomized controlled trials (RCTs) comparing early versus late initiation of RRT in patients with AKI were included. The primary outcome measures were all-cause mortality and dialysis dependence on day 90. Secondary outcome measures were length of stay, recovery of renal functions, and adverse events. Data Extraction: Two authors independently performed study selection and data extraction using data extraction forms. Data Synthesis: A total of 14 RCTs with 5,234 participants were included. Three trials had low risk of bias in all the domains. There was no significant difference in the overall mortality (risk ratio (RR): 0.99; 95% confidence interval (CI): 0.89, 1.10; moderate certainty of evidence), day 30 mortality (RR: 1.0; 95% CI: 0.91, 1.09; high certainty of evidence), day 90 mortality (RR: 1.00; 95% CI: 0.88, 1.13; high certainty of evidence), and ICU mortality (RR: 1.00; 95% CI: 0.90, 1.10; moderate certainty of evidence) between the early versus late RRT. Dialysis dependence on day 90 was significantly higher in the patients assigned to early RRT (RR: 1.55; 95% CI: 1.15, 2.09; moderate certainty of evidence). The treatment-emergent adverse events (hypophosphatemia and hypotension) were significantly higher in the patients assigned to early RRT. Conclusion: There is no added benefit of early initiation of RRT in patient with AKI; this may lead to treatment-emergent adverse events. Delaying the initiation of RRT with close monitoring and initiating RRT for emergent indications should be the acceptable criterion in critical care nephrology. Prospero Registration: CRD42016043092.

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