Objectives: The optimal time to initiate renal replacement therapy in critically ill patients with acute kidney injury is controversial. We investigated the effect of such earlier versus later initiation of renal replacement therapy on the primary outcome of 28-day mortality and other patient-centered secondary outcomes. Design: We searched MEDLINE (via PubMed), EMBASE, and Cochrane databases to July 17, 2020, and included randomized controlled trials comparing earlier versus later renal replacement therapy. Setting: Multiple centers involved in eight trials. Patients: Total of 4,588 trial participants. Intervention: Two independents investigators screened and extracted data using a predefined form. We selected randomized controlled trials in critically ill adult patients with acute kidney injury and compared of earlier versus later initiation of renal replacement therapy regardless of modality. Measurements and Main Results: Overall, 28-day mortality was similar between earlier and later renal replacement therapy initiation (38.43% vs 38.06%, respectively; risk ratio, 1.01; [95% CI, 0.94–1.09]; I2 = 0%). Earlier renal replacement therapy, however, shortened hospital length of stay (mean difference, –2.14 d; [95% CI, –4.13 to –0.14]) and ICU length of stay (mean difference, –1.18 d; [95% CI, –1.95 to –0.42]). In contrast, later renal replacement therapy decreased the use of renal replacement therapy (relative risk, 0.69; [95% CI, 0.58–0.82]) and lowered the risk of catheter-related blood stream infection (risk ratio, 0.50, [95% CI, 0.29–0.86). Among survivors, renal replacement therapy dependence at day 28 was similar between earlier and later renal replacement therapy initiation (risk ratio, 0.98; [95% CI, 0.66–1.40]). Conclusions: Earlier or later initiation of renal replacement therapy did not affect mortality. However, earlier renal replacement therapy was associated with significantly shorter ICU and hospital length of stay, whereas later renal replacement therapy was associated with decreased use of renal replacement therapy and decreased risk of catheter-related blood stream infection. These findings can be used to guide the management of critically ill patients with acute kidney injury. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). Drs. Naorungroj, Neto, Eastwood, and Bellomo contributed to conceptualization and methodology. Drs. Naorungroj, Neto, Yanase, Bagshaw, and Wald contributed to material preparation and analysis. Dr. Naorungroj contributed to writing-original draft preparation. Drs. Naorungroj, Neto, Yanase, Bagshaw, Wald, and Bellomo contributed to writing-review and editing. Each author contributed important intellectual content during article drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. Dr. Neto reported receiving lecture fee from Drager outside the submitted work. Dr. Yanase reported receiving scholarship for PhD course in Monash University from Japan Student Services Organization and Endeavour Scholarship. Dr. Wald reports receiving speaker fees and unrestricted research funding from Baxter. Dr. Bagshaw reported receiving fees for scientific advisory and grants from Baxter; he reported receiving fees for scientific advisory from Diagnostics and Spectral Medical, Canada, all outside the submitted work; he is supported by a Canada Research Chair in Critical Care Nephrology. Dr. Bellomo reported receiving grants from Baxter International outside the submitted work. The remaining authors have disclosed that they have no potential conflicts of interest. Registration: The study was registered with the Prospective Register of Systematic Reviews (CRD42020188951) on May 27, 2020. For information regarding this article, E-mail: rinaldo.bellomo@austin.org.au Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
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