• François Grolleau, Raphaël Porcher, Saber Barbar, David Hajage, Abderrahmane Bourredjem, QuenotJean-PierreJPDepartment of Intensive Care, François Mitterrand University Hospital, Lipness Team, INSERM Research Center, LNC-UMR1231 and LabEx LipSTIC, and INSERM CIC 1432, Clinical Epidemiology, University of Burgundy, Dijon, France., Didier Dreyfuss, and Stéphane Gaudry.
• Centre of Research in Epidemiology and Statistics (CRESS), Université de Paris, French Institute of Health and Medical Research (INSERM U1153), French National Research Institute for Agriculture, Food, and Environment (INRAE), Paris, France. francois.grolleau@aphp.fr.
• Crit Care. 2022 Mar 21; 26 (1): 64.

BackgroundTrials comparing early and delayed strategies of renal replacement therapy in patients with severe acute kidney injury may have missed differences in survival as a result of mixing together patients at heterogeneous levels of risks. Our aim was to evaluate the heterogeneity of treatment effect on 60-day mortality from an early vs a delayed strategy across levels of risk for renal replacement therapy initiation under a delayed strategy.MethodsWe used data from the AKIKI, and IDEAL-ICU randomized controlled trials to develop a multivariable logistic regression model for renal replacement therapy initiation within 48 h after allocation to a delayed strategy. We then used an interaction with spline terms in a Cox model to estimate treatment effects across the predicted risks of RRT initiation.ResultsWe analyzed data from 1107 patients (619 and 488 in the AKIKI and IDEAL-ICU trial respectively). In the pooled sample, we found evidence for heterogeneous treatment effects (P = 0.023). Patients at an intermediate-high risk of renal replacement therapy initiation within 48 h may have benefited from an early strategy (absolute risk difference, - 14%; 95% confidence interval, - 27% to - 1%). For other patients, we found no evidence of benefit from an early strategy of renal replacement therapy initiation but a trend for harm (absolute risk difference, 8%; 95% confidence interval, - 5% to 21% in patients at intermediate-low risk).ConclusionsWe have identified a clinically sound heterogeneity of treatment effect of an early vs a delayed strategy of renal replacement therapy initiation that may reflect varying degrees of kidney demand-capacity mismatch.© 2022. The Author(s).

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