title: Comparison of two strategies for initiating renal replacement therapy in the intensive care unit: study protocol for a randomized controlled trial (AKIKI).
abstract: BACKGROUND
  There is currently no validated strategy for the timing of renal replacement therapy (RRT) for acute kidney injury (AKI) in the intensive care unit (ICU) when short-term life-threatening metabolic abnormalities are absent. No adequately powered prospective randomized study has addressed this issue to date. As a result, significant practice heterogeneity exists and may expose patients to either unnecessary hazardous procedures or undue delay in RRT.
  
  
  METHODS
  This is a multicenter, prospective, randomized, open-label parallel-group clinical trial that compares the effect of two RRT initiation strategies on overall survival of critically ill patients receiving intravenous catecholamines or invasive mechanical ventilation and presenting with AKI classification stage 3 (KDIGO 2012). In the 'early' strategy, RRT is initiated immediately. In the 'delayed' strategy, clinical and metabolic conditions are closely monitored and RRT is initiated only when one or more events (severity criteria) occur, including: oliguria or anuria for more than 72 hours after randomization, serum urea concentration >40 mmol/l, serum potassium concentration >6 mmol/l, serum potassium concentration >5.5 mmol/l persisting despite medical treatment, arterial blood pH <7.15 in a context of pure metabolic acidosis (PaCO2 < 35 mmHg) or in a context of mixed acidosis with a PaCO2 ≥ 50 mmHg without possibility of increasing alveolar ventilation, acute pulmonary edema due to fluid overload despite diuretic therapy leading to severe hypoxemia requiring oxygen flow rate >5 l/min to maintain SpO2 > 95% or FiO2 > 50% under invasive or noninvasive mechanical ventilation. The primary outcome measure is overall survival, measured from randomization (D0) until death, regardless of the cause. The minimum follow-up duration for each patient will be 60 days. Two interim analyses are planned, blinded to group allocation. It is expected that there will be 620 subjects in all.
  
  
  CONCLUSIONS
  The AKIKI study will be one of the very few large randomized controlled trials evaluating mortality according to the timing of RRT in critically ill patients with AKI classification stage 3 (KDIGO 2012). Results should help clinicians decide when to initiate RRT.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01932190.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Louis Mourier, Service de Réanimation Médico-Chirurgicale, 178 rue des Renouillers, F-92700, Colombes, France. stephanegaudry@gmail.com.|Université Paris Diderot, Sorbonne Paris Cité, ECEVE, UMRS 1123, F-75010, Paris, France. stephanegaudry@gmail.com.|INSERM, ECEVE, U1123, F-75010, Paris, France. stephanegaudry@gmail.com.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gaudry
authors.affiliation: INSERM, CIC-EC 1425, UMR 1123, Paris, France. david.hajage@lmr.aphp.fr.|Assistance Publique-Hôpitaux de Paris, Hôpital Louis Mourier, Département d'Epidémiologie et Recherche Clinique, Paris, France. david.hajage@lmr.aphp.fr.|Université Paris Diderot, UMR 1123, Sorbonne Paris Cité, Paris, France. david.hajage@lmr.aphp.fr.
authors.forename: David
authors.initials: D
authors.lastname: Hajage
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, DHU A-TVB, Service de Réanimation Médicale, Créteil, France. frederique.schortgen@hmn.aphp.fr.
authors.forename: Fréderique
authors.initials: F
authors.lastname: Schortgen
authors.affiliation: Medical-Surgical Intensive Care Unit, District Hospital Center, La Roche-sur-Yon, France. laurent.martin-lefevre@chd-vendee.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Martin-Lefevre
authors.affiliation: INSERM, CIC-EC 1425, UMR 1123, Paris, France. florence.tubach@bch.aphp.fr.|Université Paris Diderot, UMR 1123, Sorbonne Paris Cité, Paris, France. florence.tubach@bch.aphp.fr.|Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Département d'Epidémiologie et Recherche Clinique, Paris, France. florence.tubach@bch.aphp.fr.
authors.forename: Florence
authors.initials: F
authors.lastname: Tubach
authors.affiliation: Service de Réanimation, CHU de Pointe à Pitre - Abymes, CHU de la Guadeloupe, Basse-Terre, France. bertrand.pons@chu-guadeloupe.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Pons
authors.affiliation: Réanimation polyvalente, CH René Dubos, 95301, Pontoise, France. eric.boulet@ch-pontoise.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Boulet
authors.affiliation: CHU Bordeaux, Hôpital Pellegrin, 33000, Bordeaux, France. alexandre.boyer@chu-bordeaux.fr.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Boyer
authors.affiliation: Département de réanimation médicale et médecine hyperbare, CHU Angers, Université d'Angers, Angers, France. nilerolle@chu-angers.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lerolle
authors.affiliation: Intensive Care Unit, Centre Hospitalier Sud Francilien, Corbeil Essonnes, France. guillaume.chevrel@ch-sud-francilien.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Chevrel
authors.affiliation: Réanimation médicale, CHU Rouen, 76000, Rouen, France. dorothee.carpentier@chu-rouen.fr.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Carpentier
authors.affiliation: Medical Intensive Care Unit, Gabriel Montpied Teaching Hospital, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France. alautrette@chu-clermontferrand.fr.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Lautrette
authors.affiliation: Medical-Surgical Intensive Care Unit, Hôpital de La Source, Centre Hospitalier Régional d'Orléans, BP 6709, , 45067, Orleans Cedex, France. anne.bretagnol@chr-orleans.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Bretagnol
authors.affiliation: Service de Pneumologie et Réanimation médicale, APHP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. julien.mayaux@psl.aphp.fr.
authors.forename: Julien
authors.initials: J
authors.lastname: Mayaux
authors.affiliation: Réanimation polyvalente, CH Victor Dupouy, 95107, Argenteil Cedex, France. marina.thirion@ch-argenteuil.fr.
authors.forename: Marina
authors.initials: M
authors.lastname: Thirion
authors.affiliation: Réanimation, CH Cholet, 49300, Cholet, France. philippe.markowicz@ch-cholet.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Markowicz
authors.affiliation: Service de Réanimation Détresses respiratoires aiguës et infections sévères, Hôpital Nord, Marseille, 13015, France. guillemette.thomas@ap-hm.fr.
authors.forename: Guillemette
authors.initials: G
authors.lastname: Thomas
authors.affiliation: Medical Intensive Care Unit, Archet I University Hospital, 151 Route Saint Antoine de Ginestière, 06200, Nice, France. dellamonica.j@chu-nice.fr.
authors.forename: Jean
authors.initials: J
authors.lastname: Dellamonica
authors.affiliation: Réanimation, CH de Beauvais, 60000, Beauvais, France. j.richecoeur@ch-beauvais.fr.
authors.forename: Jack
authors.initials: J
authors.lastname: Richecoeur
authors.affiliation: Medical Intensive Care Unit, Saint-Etienne University Hospital, Avenue Albert Raymond, Saint-Priest en Jarez, France. michael.darmon@chu-st-etienne.fr.
authors.forename: Michael
authors.initials: M
authors.lastname: Darmon
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, DHU A-TVB, Service de Réanimation Médicale, Créteil, France. nicolas.de-prost@hmn.aphp.fr.|CARMAS research group, UPEC-Université Paris-Est Créteil Val de Marne, Créteil, France. nicolas.de-prost@hmn.aphp.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: de Prost
authors.affiliation: Réanimation médicale, Hôpital de la Croix Rousse, 69000, Lyon, France. hodane.yonis@chu-lyon.fr.
authors.forename: Hodane
authors.initials: H
authors.lastname: Yonis
authors.affiliation: Réanimation Médicale et Toxicologique, Hôpital Lariboisière, INSERM U1144, Université Paris Diderot, Paris, France. bruno.megarbane@lrb.aphp.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Megarbane
authors.affiliation: Réanimation, CH Poissy Saint Germain en laye, 78300, Poissy, France. yloubiere@chi-poissy-st-germain.fr.
authors.forename: Yann
authors.initials: Y
authors.lastname: Loubières
authors.affiliation: Service de Pneumologie et Réanimation, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris and Université Pierre et Marie Curie, 4 Rue de la Chine, 75020, Paris, France. clarisseblayau@gmail.com.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Blayau
authors.affiliation: Medical intensive care unit, University medical center and INSERM U-1088, University of Picardie, Amiens, France. maizel.julien@chu-amiens.fr.
authors.forename: Julien
authors.initials: J
authors.lastname: Maizel
authors.affiliation: Réanimation médico-chirurgicale, CH Versailles, 78000, Versailles, France. bzuber@ch-versailles.fr.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Zuber
authors.affiliation: Centre de Réanimation, Hôpital R. Salengro, CHRU de Lill, Rue E. Laine, 59037, Lille Cedex, France. saadalla.nseir@chru-lille.fr.
authors.forename: Saad
authors.initials: S
authors.lastname: Nseir
authors.affiliation: AP-HP, Hôpital Saint Antoine, Service de Réanimation Médicale, Paris, F-75012, France. naike.bige@sat.aphp.fr.
authors.forename: Naïke
authors.initials: N
authors.lastname: Bigé
authors.affiliation: INSERM, CIC-EC 1425, UMR 1123, Paris, France. isabelle.hoffmann@bch.aphp.fr.|Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Département d'Epidémiologie et Recherche Clinique, Paris, France. isabelle.hoffmann@bch.aphp.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hoffmann
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Louis Mourier, Service de Réanimation Médico-Chirurgicale, 178 rue des Renouillers, F-92700, Colombes, France. jean-damien.ricard@lmr.aphp.fr.|Université Paris Diderot, Sorbonne Paris Cité, IAME, UMRS 1137, F-75018, Paris, France. jean-damien.ricard@lmr.aphp.fr.|INSERM, IAME, U1137, F-75018, Paris, France. jean-damien.ricard@lmr.aphp.fr.
authors.forename: Jean-Damien
authors.initials: JD
authors.lastname: Ricard
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Louis Mourier, Service de Réanimation Médico-Chirurgicale, 178 rue des Renouillers, F-92700, Colombes, France. didier.dreyfuss@lmr.aphp.fr.|Université Paris Diderot, Sorbonne Paris Cité, IAME, UMRS 1137, F-75018, Paris, France. didier.dreyfuss@lmr.aphp.fr.|INSERM, IAME, U1137, F-75018, Paris, France. didier.dreyfuss@lmr.aphp.fr.|Present address: Intensive care unit, Hôpital Louis Mourier, 178 rue des Renouillers, 92110, Colombes, France. didier.dreyfuss@lmr.aphp.fr.
authors.forename: Didier
authors.initials: D
authors.lastname: Dreyfuss
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D015415:Biomarkers / Q000097:blood; D002985:Clinical Protocols; D016638:Critical Illness; D003661:Decision Support Techniques; D005602:France; D006801:Humans; D015601:Injury Severity Score; D007362:Intensive Care Units; D018579:Patient Selection; D011237:Predictive Value of Tests; D011446:Prospective Studies; D017582:Renal Replacement Therapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D061665:Time-to-Treatment; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers