Personalization of renal replacement therapy initiation: a secondary analysis of the AKIKI and IDEAL-ICU trials
François Grolleau,
Raphaël Porcher,
Saber Barbar,
David Hajage,
Abderrahmane Bourredjem,
Jean-Pierre Quenot,
Didier Dreyfuss,
Stéphane Gaudry
Affiliations
François Grolleau
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)
Raphaël Porcher
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)
Saber Barbar
Intensive Care Department, Nîmes University Hospital, University of Montpellier
David Hajage
INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié-Salpêtrière, Département de Santé Publique, Centre de Pharmacoépidémiologie, Sorbonne Université
Abderrahmane Bourredjem
Clinical Epidemiology Unit, INSERM CIC1432, Dijon, and Clinical Investigation Center, Clinical Epidemiology/Clinical Trials Unit, Dijon Bourgogne University Hospital
Jean-Pierre Quenot
Department 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
Didier Dreyfuss
Université de Paris, Service de Médecine Intensive-Réanimation, Hôpital Louis Mourier, AP-HP and INSERM, UMR S1155 “Common and Rare Kidney Diseases: From Molecular Events To Precision Medicine”, Sorbonne Université
Stéphane Gaudry
Service de Réanimation Médico-Chirurgicale, Hôpital Avicenne, APHP, UFR SMBH, Université Sorbonne Paris Nord, Bobigny, French National Institute of Health and Medical Research (INSERM), Common and Rare kidney Diseases (CORAKID), Hôpital Tenon
Abstract Background Trials 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. Methods We 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. Results We 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). Conclusions We 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.
