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Randomized Controlled Trial
. 2025 Apr 1;53(4):e897-e907.
doi: 10.1097/CCM.0000000000006616. Epub 2025 Mar 3.

Time to Renal Replacement Therapy Initiation in Critically Ill Patients With Acute Kidney Injury: A Secondary Analysis of the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial

Rachel Jeong  1   2 , Sean M Bagshaw  3 , Ehsan Ghamarian  4 , Andrea Harvey  5 , Michael Joannidis  6 , Brian Kirkham  4 , Danny McAuley  7   8 , Marlies Ostermann  9 , Jean-Pierre Quenot  10   11   12 , Paul J Young  13   14   15   16 , Ron Wald  17   18   19 ; STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Time to Renal Replacement Therapy Initiation in Critically Ill Patients With Acute Kidney Injury: A Secondary Analysis of the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial

Rachel Jeong et al. Crit Care Med. .

Abstract

Objectives: Among critically ill patients with severe acute kidney injury (AKI) who lack emergent indications for renal replacement therapy (RRT), a strategy of preemptive RRT initiation does not lead to improved outcomes. However, for patients with persistent AKI and without urgent indications for RRT, the safety of prolonged delays in RRT initiation is unclear. We sought to assess the association between progressively longer delays in RRT initiation and clinical outcomes.

Design: A post hoc secondary analysis.

Setting: The multinational STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial.

Patients: Participants allocated to the standard strategy of the STARRT-AKI trial.

Interventions: The exposure was time from randomization to RRT initiation, evaluated in quartiles and as a continuous variable.

Measurements and main results: The primary outcome was all-cause mortality at 90 days. Secondary outcomes were RRT dependence, RRT-free days, and hospital-free days, all at 90 days, as well length of ICU and hospital stay. Of the 1462 participants allocated to the standard strategy group, 903 (62%) received RRT. Median time (interquartile range) to RRT initiation was 12.1 hours (8.3-13.8 hr), 24.5 hours (21.8-26.5 hr), 46.8 hours (35.2-52.1 hr), and 96.1 hours (76.7-139.2 hr) in quartiles 1-4, respectively. Prolonged time to RRT initiation was associated with a lower risk of death at 90 days (quartile 4 vs. 1: adjusted odds ratio, 0.63 [95% CI, 0.42-0.94]); further analyses using cubic splines and inverse probability weighting to account for immortal time bias showed no association with the risk of death. There was no association between time to RRT initiation and RRT-free days, hospital-free days, or lengths of ICU or hospital stay. Longer delay to RRT initiation had a linear association with RRT dependence at 90 days.

Conclusions: Among patients with no urgent indications and who received RRT in the standard strategy of the STARRT-AKI trial, longer deferral of RRT initiation was not associated with a higher risk of mortality.

Keywords: acute kidney injury; critical care; dialysis; renal replacement therapy; timing.

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Conflict of interest statement

Drs. Bagshaw and Joannidis received funding from BioMerieux and SphingoTec. Dr. Bagshaw received fees from Baxter for speaking and scientific advisory; he received fees from BioPorto for clinical adjudication and scientific advisory; he received fees from Novartis for scientific advisory; he received fees from the Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis (I-SPY-COVID) for Data Safety Monitoring; he received fees from Sea Star Medical for scientific advisory; and he is supported by a Canada Research Chair in Critical Care Outcomes and Systems Evaluation. Dr. Ghamarian’s institution received funding from Unity Health Toronto—Applied Health Research Centre; they disclosed work for hire. Dr. Joannidis’ institution received funding from Baxter Healthcare Corp, AM-Pharma, CLS Behring, Fresenius, Takeda, and Fresenius; he received funding from AOP Health. Drs. Joannidis and McAuley received funding from Novartis. Dr. McAuley’s institution received funding from the National Institute for Health and Care Research; he received funding from Bayer, GlaxoSmithKline, Boehringer Ingelheim, Aptarion, Direct Biologics, Aviceda, Eli Lilly, SOBI, Vir Biotechnology, and Faron Pharmaceuticals. Dr. Ostermann secured funding from Baxter and Biomerieux, which was paid into an institutional research fund. Dr. Wald received support for article research from the CIHR; he received unrestricted research funding, speaker fees, and consulting fees from Baxter. The remaining authors have disclosed that they do not have any potential conflicts of interest.

References

    1. Hoste EA, Bagshaw SM, Bellomo R, et al.: Epidemiology of acute kidney injury in critically ill patients: The multinational AKI-EPI study. Intensive Care Med. 2015; 41:1411–1423
    1. James MT, Bhatt M, Pannu N, et al.: Long-term outcomes of acute kidney injury and strategies for improved care. Nat Rev Nephrol. 2020; 16:193–205
    1. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group: KDIGO clinical practice guideline for acute kidney injury. Kid Inter Supp. 2012; 2:1–138
    1. Gaudry S, Hajage D, Schortgen F, et al.; AKIKI Study Group: Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med. 2016; 375:122–133
    1. Barbar SD, Clere-Jehl R, Bourredjem A, et al.; IDEAL-ICU Trial Investigators and the CRICS TRIGGERSEP Network: Timing of renal-replacement therapy in patients with acute kidney injury and sepsis. N Engl J Med. 2018; 379:1431–1442

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