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N Engl J Med. 2016 Jul 14;375(2):122-33. doi: 10.1056/NEJMoa1603017. Epub 2016 May 15.

Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit.

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From Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Louis Mourier, Service de Réanimation Médico-Chirurgicale, Colombes (S.G., J.-D.R., D.D.), Universite Paris Diderot, Sorbonne Paris Cité, Epidémiologie Clinique-Évaluation Économique Appliqué aux Populations Vulnérables (ECEVE) (S.G., D.H., F.T.), Institut National de la Santé et de la Recherche Médicale (INSERM), ECEVE, Centre d'investigation Clinique-Epidémiologie Clinique (CIC-EC) 1425 (S.G., D.H., F.T.), APHP, Hôpital Louis Mourier, Département d'Epidémiologie et Recherche Clinique, CIC-EC 1425 (D.H.), Service de Pneumologie et Réanimation Médicale, APHP, Groupe Hospitalier Pitié-Salpêtrière (J. Mayaux), Réanimation Médicale et Toxicologique, Hôpital Lariboisière, INSERM Unité 1144, Université Paris Diderot (B.M.), APHP, Hôpital Bichat, Département d'Epidémiologie et Recherche Clinique, CIC-EC 1425 (F.T.), and Université Paris Diderot, Infection, Antimicrobiens, Modélisation, Evolution (IAME), Unité Mixte de Recherche (UMR) 1137, Sorbonne Paris Cité (J.-D.R., D.D.), Paris, APHP, Hôpitaux Universitaires Henri Mondor, Service de Réanimation Médicale (F.S.), and APHP, Hôpitaux Universitaires Henri Mondor, Département Hospitalo-Universitaire Ageing Thorax-Vessels-Blood, Service de Réanimation Médicale, Cardiovascular and Respiratory Manifestations of Acute Lung Injury and Sepsis (CARMAS) Research Group and Université Paris-Est Créteil Val de Marne (N.P.), Créteil, Réanimation Médico-Chirurgicale, Centre Hospitalier Général, La Roche-sur-Yon (L.M.-L.), Service de Réanimation, Centre Hospitalier Universitaire (CHU) de Pointe à Pitre-Abymes, Guadeloupe (B.P., G.T.), Réanimation Polyvalente, CH René Dubos, Pontoise (E.B.), Réanimation Médicale CHU Bordeaux, Hôpital Pellegrin, Bordeaux (A. Boyer), Service de Réanimation, CH Sud Francilien, Corbeil Essonne (G.C.), Département de Réanimation Médicale et Médecine Hyperbare, CHU Angers, Université d'Angers,



The timing of renal-replacement therapy in critically ill patients who have acute kidney injury but no potentially life-threatening complication directly related to renal failure is a subject of debate.


In this multicenter randomized trial, we assigned patients with severe acute kidney injury (Kidney Disease: Improving Global Outcomes [KDIGO] classification, stage 3 [stages range from 1 to 3, with higher stages indicating more severe kidney injury]) who required mechanical ventilation, catecholamine infusion, or both and did not have a potentially life-threatening complication directly related to renal failure to either an early or a delayed strategy of renal-replacement therapy. With the early strategy, renal-replacement therapy was started immediately after randomization. With the delayed strategy, renal-replacement therapy was initiated if at least one of the following criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg per deciliter, or oliguria for more than 72 hours after randomization. The primary outcome was overall survival at day 60.


A total of 620 patients underwent randomization. The Kaplan-Meier estimates of mortality at day 60 did not differ significantly between the early and delayed strategies; 150 deaths occurred among 311 patients in the early-strategy group (48.5%; 95% confidence interval [CI], 42.6 to 53.8), and 153 deaths occurred among 308 patients in the delayed-strategy group (49.7%, 95% CI, 43.8 to 55.0; P=0.79). A total of 151 patients (49%) in the delayed-strategy group did not receive renal-replacement therapy. The rate of catheter-related bloodstream infections was higher in the early-strategy group than in the delayed-strategy group (10% vs. 5%, P=0.03). Diuresis, a marker of improved kidney function, occurred earlier in the delayed-strategy group (P<0.001).


In a trial involving critically ill patients with severe acute kidney injury, we found no significant difference with regard to mortality between an early and a delayed strategy for the initiation of renal-replacement therapy. A delayed strategy averted the need for renal-replacement therapy in an appreciable number of patients. (Funded by the French Ministry of Health; number, NCT01932190.).

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