Timing of renal-replacement therapy in patients with acute kidney injury and sepsis: a systematic review and meta-analysis

Abstract Background The optimal timing for initiating renal replacement therapy (RRT) in sepsis-associated acute kidney injury (AKI) patients remains controversial. Early RRT initiation offers benefits by preventing metabolic complications and fluid overload, while delayed initiation avoids unnecessary procedures and conserves resources. This systematic review and meta-analysis aimed to compare early versus delayed RRT strategies in adult patients with sepsis-associated AKI. Methods We conducted a comprehensive search on PubMed, Scopus, Web of Science, and Cochrane CENTRAL from inception to February 2026. We included randomized controlled trials (RCTs) and observational cohorts comparing early versus delayed RRT initiation in patients with sepsis-associated AKI. Outcomes included 28-day and 90-day mortality, multi-organ dysfunction score (MODS), and intensive care unit (ICU) and hospital length of stay. Data were pooled using random-effects models. Results Fifteen studies (4 RCTs, 11 retrospective cohorts) comprising 6,289 patients were included. Early RRT was associated with significant reduction in 28-day mortality compared to delayed RRT (RR 0.81, 95% CI: 0.68–0.95, p  = 0.01; I²=31.38%). However, trim-and-fill analysis suggested potential publication bias, with adjusted estimates showing non-significance (RR 0.88, 95% CI: 0.75–1.04). No significant differences were observed for 90-day mortality (RR 0.85, 95% CI: 0.69–1.04, p  = 0.12), MODS (MD 0.24, 95% CI: -0.94–1.42, p  = 0.69), ICU length of stay (MD -1.76, 95% CI: -4.18–0.66, p  = 0.15), or hospital length of stay (MD 0.34, 95% CI: -3.24–3.92, p  = 0.85). Conclusion Early RRT initiation in sepsis-associated AKI was associated with reduction in 28-day mortality rates but did not result in any differences of 90-days mortality rates, and was not associated with improvements in MODS, suggesting that timing alone may not substantially alter long-term outcomes in this high-risk population. These findings are driven from mixed study designs with heterogeneity among the included patients, underscoring the need for more individualized approaches to RRT initiation in the future trials. Trial registration Not applicable.