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One-Year Prognosis of Kidney Injury at Discharge From the ICU: A Multicenter Observational Study

Legrand, Matthieu MD, PhD1,2,3; Hollinger, Alexa MD1,2,4; Vieillard-Baron, Antoine MD, PhD5,6,7; Dépret, François MD1,2,3; Cariou, Alain MD, PhD8; Deye, Nicolas MD, PhD9; Fournier, Marie-Céline RN1,2; Jaber, Samir MD, PhD10; Damoisel, Charles MD1; Lu, Qin MD, PhD11; Monnet, Xavier MD, PhD12; Rennuit, Isabelle MD13; Darmon, Michael MD, PhD14; Zafrani, Lara MD, PhD14; Leone, Marc MD, PhD15; Guidet, Bertrand MD, PhD16; Friedman, Diane MD17; Sonneville, Romain MD, PhD18; Montravers, Philippe MD, PhD19; Pili-Floury, Sébastien MD, PhD20; Lefrant, Jean-Yves MD21,22; Duranteau, Jacques MD, PhD23; Laterre, Pierre-François MD, PhD24; Brechot, Nicolas MD25; Oueslati, Haikel MD1; Cholley, Bernard MD, PhD26; Launay, Jean-Marie PharmD, PhD2,27; Ishihara, Shiro MD, PhD1,28; Sato, Naoki MD, PhD1,28; Mebazaa, Alexandre MD, PhD1,2,3; Gayat, Etienne MD, PhD1,2,3; on behalf of the French and euRopean Outcome reGistry in ICUs (FROG-ICU) Investigators

doi: 10.1097/CCM.0000000000004010
Online Clinical Investigations
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Objectives: The association between outcome and kidney injury detected at discharge from the ICU using different biomarkers remains unknown. The objective was to evaluate the association between 1-year survival and kidney injury at ICU discharge.

Design: Ancillary investigation of a prospective observational study.

Setting: Twenty-one ICUs with 1-year follow-up.

Patients: Critically ill patients receiving mechanical ventilation and/or hemodynamic support for at least 24 hours were included.

Interventions: Serum creatinine, plasma Cystatin C, plasma neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, plasma Proenkephalin A 119-159, and estimated glomerular filtration rate (on serum creatinine and plasma Cystatin C) were measured at ICU discharge among ICU survivors.

Measurements and Main Results: The association between kidney biomarkers at discharge and mortality was estimated using logistic model with and without adjustment for prognostic factors previously identified in this cohort. Subgroup analyses were performed in patients with discharge serum creatinine less than 1.5-fold baseline at ICU discharge. Among 1,207 ICU survivors included, 231 died during the year following ICU discharge (19.2%). Estimated glomerular filtration rate was significantly lower and kidney injury biomarkers higher at discharge in nonsurvivors. The association between biomarker levels or estimated glomerular filtration rate and mortality remained after adjustment to potential cofounding factors influencing outcome. In patients with low serum creatinine at ICU discharge, 25–47% of patients were classified as subclinical kidney injury depending on the biomarker. The association between kidney biomarkers and mortality remained and mortality was higher than patients without subclinical kidney injury. The majority of patients who developed acute kidney injury during ICU stay had elevated biomarkers of kidney injury at discharge even with apparent recovery based on serum creatinine (i.e., subclinical acute kidney disease).

Conclusions: Elevated kidney biomarkers measured at ICU discharge are associated with poor 1-year outcome, including in patients with low serum creatinine at ICU discharge.

1Department of Anaesthesiology, Critical Care Medicine and Burn unit, AP-HP, Saint Louis and Lariboisière University Hospitals, Paris, France.

2INSERM UMR-S942, Institut National de la Santé et de la Recherche Médicale (INSERM), Lariboisière hospital and INI-CRCT network, Paris, France.

3Université Paris Diderot, F-75475, Paris, France.

4Department of Anaesthesia, Surgical Intensive Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, Basel, Switzerland.

5University Hospital Ambroise Paré, Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Boulogne-Billancourt, France.

6INSERM U-1018, CESP, Team 5, University of Versailles Saint-Quentin en Yvelines, Villejuif, France.

7Faculty of Medicine Paris Ile-de-France Ouest, University of Versailles Saint-Quentin en Yvelines, Saint-Quentin en Yvelines, France.

8Medical Intensive Care Unit, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.

9Medical Intensive Care Unit, Hôpitaux Universitaires Saint Louis, Lariboisière, Assistance Publique, Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, UMR-S 942, INSERM, Paris, France.

10Intensive Care Unit, Anaesthesia and Critical Care Department, Saint Eloi Teaching Hospital, Centre Hospitalier, Montpellier, France.

11Multidisciplinary Intensive Care Unit, Department of Anesthesiology and Critical Care Medicine, La Pitié-Salpêtrière Hospital, Assistance Publique Hôpitaux de Paris, UPMC Paris 6, Paris, France.

12Medical Intensive Care Unit, Bicêtre Hospital, Paris-Sud University Hospitals, Inserm UMR_S999, Paris-Sud University, Le Kremlin-Bicetre, France.

13Department of Anesthesiology and Critical Care, Beaujon Hospital, Assistance Publique Hôpitaux de Paris University, Clichy, France.

14Medical Intensive Care Unit, Hôpital Saint-Louis, ECSTRA Team, Biostatistics and Clinical Epidemiology, UMR 1153 (Center of Epidemiology and Biostatistics Sorbonne Paris Cité, CRESS), INSERM, Université Paris Diderot Sorbonne, Paris, France.

15Aix Marseille University, APHM, Department of Anesthesiology and Critical Care Medicine, Marseille, France.

16Medical Intensive Care Unit, Department of Intensive Care, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France.

17Department of Anesthesiology and Intensive Care, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Paris Cardiovascular Research Center-INSERM U970 (PARCC), Paris Sudden Death Expertise Center, Paris, France.

18Department of Intensive Care Medicine and Infectious Diseases, Univ Paris Diderot, Sorbonne Paris Cité, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude, Paris, France.

19Department of Anesthesiology and Intensive Care, Bichat University Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Sorbonne Paris Cité, Paris, France.

20Department of Anesthesiology and Intensive Care Medicine, Besançon University Hospital, Besançon, France EA 3920, University of Bourgogne Franche-Comté, Besançon, France.

21Department of Anesthesiology, Critical Care, Emergency and Pain Medicine, Nimes University Hospital, Nîmes, France.

22Female characteristics of endothelium dysfunction, EA 2992, Faculté de Médecine de Nîmes, Université Montpellier 1, Nîmes, France.

23Department of Anesthesiology and Critical Care, Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, Paris, France.

24Department of Critical Care Medicine, Saint Luc University Hospital, Université Catholique de Louvain, Brussels, Belgium.

25INSERM, U833, Paris, France, Laboratoire Angiogenèse Embryonnaire et Pathologique, Collège de France, Paris, France.

26Department of Anesthesiology and Intensive Care, Hôpital Européen Georges Pompidou University Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes-Paris 5, Paris, France.

27Centre for Biological Resources BB-0033-00064, Lariboisière Hospital, Paris, France.

28Nippon Medical School Musashi-Kosugi Hospital, Kanagawa, Japan.

The complete list of French and euRopean Outcome reGistry in ICUs (FROG-ICU) Investigators is: Etienne Gayat, Alain Cariou, Nicolas Deye, Antoine Vieillard-Baron, Samir Jaber, Charles Damoisel, Qin Lu, Xavier Monnet, Isabelle Rennuit, Elie Azoulay, Marc Léone, Heikel Oueslati, Bertrand Guidet, Diane Friedman, Antoine Tesnière, Romain Sonneville, Philippe Montravers, Sébastien Pili-Floury, Jean-Yves Lefrant, Jacques Duranteau, Pierre-François Laterre, Nicolas Brechot, Karine Chevreul, Morgane Michel, Bernard Cholley, Matthieu Legrand, Jean-Marie Launay, Eric Vicaut, Mervyn Singer, Matthieu Resche-Rigon, and Alexandre Mebazaa.

This work was performed at Hôpital Lariboisière, Paris, France; Hôpital Saint-Louis, Paris, France; Hôpital Bichat, Paris, France; Hôpital Beaujon, Paris, France; Hôpital Cochin, Paris, France; Hôpital Bicêtre, Le Kremlin Bicêtre, France; Hôpital Raymond Poincaré, Garches, France; Hôpital Saint-Antoine, Paris, France; Hôpital Nord, Marseille, France; Hôpital de la Pitié-Salpêtrière, Paris, France; Hôpital Saint-Eloi, Montpellier, France; Hôpital Ambroise Paré, Boulogne, France; Hôpital Caremeau, Nîmes, France; Hôpital Jean Minjoz, Besançon, France; Hôpital Saint-Luc, Bruxelles, Belgique.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

French and euRopean Outcome reGistry in ICU (ClinicalTrials.gov Identifier NCT01367093) was funded by the Programme Hospitalier de la Recherche Clinique (AON 10-216) and by a research grant from the Société Française d’Anesthésie Réanimation. Abbott, Sphingotec, Roche Diagnostics, and Critical Diagnostics provided unrestricted free kits to Assistance Publique-Hôpitaux de Paris to conduct biomarker analyses.

Dr. Legrand disclosed French and euRopean Outcome reGistry in ICU (ClinicalTrials.gov Identifier NCT01367093) was funded by the Programme Hospitalier de la Recherche Clinique (AON 10-216) and by a research grant from the Société Française d’Anesthésie Réanimation; he received lecture fees from Alere, Fresenius, and Gilead and Consulting fees from Adrenomed. Dr. Deye’s institution received funding from Zoll and Bard for travel and lecture fees. Dr. Fournier’s institution received funding from Programme Hospitalier de la Recherche Clinique (AON 10-216) and a research grant from the Société Française d’Anesthésie Réanimation. Dr. Monnet received funding from Pulsion Medical Systems, and he received support for article research from Assistance publique hôpitaux de Paris. Dr. Darmon received consulting fees from Sanofi and Gilead-Kite, research support from Astute Medical and Merck Sharp & Dohme, (MSD), and speaker fees from MSD, Gilead-Kite, and Astellas. Dr. Zafrani received funding from Jazz Pharmaceuticals (research grant). Dr. Leone received funding from MSD, Pfizer, Amomed, Aguettant (consulting), Octapharma (lecture), Aspen (lecture), and Orion (lecture). Dr. Pili-Floury received funding from Pfizer. Dr. Sato disclosed work for hire. Dr. Mebazaa has received speaker’s honoraria from Novartis, Orion, Servier, and fee as member of advisory board and/or Steering Committee from Cardiorentis, Adrenomed, Sphingotec, Sanofi, Roche, Abbott, and Bristol-Myers Squibb. Dr. Gayat’s institution received funding from programme hospitalier de recherche clinique 2011, Retia Medical, and Société Française d’Anesthésie Réanimation; he received funding from Adrenomed, Roche Diagnostics and Magnisense, lecture fees from Edwards LifeScience. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Trial registration: ClinicalTrials.gov NCT01367093; registered on June 6, 2011.

For information regarding this article, E-mail: matthieu.legrand@aphp.fr

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