Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial
Stéphane Gaudry
(1, 2)
,
David Hajage
(3, 4, 5)
,
Laurent Martin-Lefevre
(6)
,
Saïd Lebbah
(5, 4)
,
Guillaume Louis
(7)
,
Sébastien Moschietto
(8)
,
Dimitri Titeca-Beauport
(9)
,
Béatrice La Combe
(10)
,
Bertrand Pons
(11)
,
Nicolas de Prost
(12)
,
Sébastien Besset
,
Alain Combes
(13)
,
Adrien Robine
,
Marion Beuzelin
(14)
,
Julio Badie
(15)
,
Guillaume Chevrel
(16)
,
Julien Bohe
(17)
,
Elisabeth Coupez
(18)
,
Nicolas Chudeau
(19)
,
Saber Barbar
(20)
,
Christophe Vinsonneau
,
Jean-Marie Forel
(21)
,
Didier Thevenin
(22)
,
Eric Boulet
,
Karim Lakhal
(23)
,
Nadia Aissaoui
(24)
,
S. Grange
(25)
,
Marc Leone
(26, 27)
,
Guillaume Lacave
(28)
,
Saad Nseir
(29)
,
Florent Poirson
(1)
,
Julien Mayaux
(30)
,
Karim Asehnoune
(31)
,
Guillaume Geri
(32)
,
Kada Klouche
(23, 33)
,
Guillaume Thiery
(34)
,
Laurent Argaud
(35)
,
Bertrand Rozec
(31)
,
Cyril Cadoz
(36)
,
Pascal Andreu
(37)
,
Jean Reignier
(31)
,
Jean-Damien Ricard
(38, 39)
,
Jean-Pierre Quenot
(37)
,
Didier Dreyfuss
(38)
1
Hôpital Avicenne [AP-HP]
2 UFR SMBH - UFR Santé, Médecine et Biologie Humaine
3 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
4 Cephepi - Centre de Pharmacoépidémiologie de l'AP-HP
5 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
6 CHD Vendée - Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon
7 L3I - Laboratoire Informatique, Image et Interaction - EA 2118
8 Centre Hospitalier Henri Duffaut (Avignon)
9 CHU Amiens-Picardie
10 UBS Lorient - Université de Bretagne Sud - Lorient
11 CELIA - Centre d'Etudes Lasers Intenses et Applications
12 Hôpital Henri Mondor
13 LSABM - Laboratoire Sciences Analytiques, Bioanalytiques, et Miniaturisation
14 Centre hospitalier de Dieppe
15 CH Belfort-Montbéliard
16 Centre Hospitalier Sud Francilien
17 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
18 CHU Gabriel Montpied [Clermont-Ferrand]
19 Centre Hospitalier Le Mans (CH Le Mans)
20 CHU Nîmes - Hôpital Universitaire Carémeau [Nîmes]
21 APHM - Assistance Publique - Hôpitaux de Marseille
22 Centre Hospitalier de Lens
23 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
24 HEGP - Hôpital Européen Georges Pompidou [APHP]
25 GEOMAS - Géomécanique, Matériaux et Structures
26 MEPHI - Microbes évolution phylogénie et infections
27 Service Anesthésie et Réanimation [Hôpital Nord - APHM]
28 CHV - Centre Hospitalier de Versailles André Mignot
29 CIC Lille - Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301
30 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
31 CHU Nantes - Centre hospitalier universitaire de Nantes
32 Hôpital Ambroise Paré [AP-HP]
33 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
34 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
35 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
36 CHR Metz-Thionville - Centre hospitalier régional Metz-Thionville
37 Service de Réanimation Médicale (CHU de Dijon)
38 Hôpital Louis Mourier - AP-HP [Colombes]
39 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
2 UFR SMBH - UFR Santé, Médecine et Biologie Humaine
3 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
4 Cephepi - Centre de Pharmacoépidémiologie de l'AP-HP
5 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
6 CHD Vendée - Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon
7 L3I - Laboratoire Informatique, Image et Interaction - EA 2118
8 Centre Hospitalier Henri Duffaut (Avignon)
9 CHU Amiens-Picardie
10 UBS Lorient - Université de Bretagne Sud - Lorient
11 CELIA - Centre d'Etudes Lasers Intenses et Applications
12 Hôpital Henri Mondor
13 LSABM - Laboratoire Sciences Analytiques, Bioanalytiques, et Miniaturisation
14 Centre hospitalier de Dieppe
15 CH Belfort-Montbéliard
16 Centre Hospitalier Sud Francilien
17 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
18 CHU Gabriel Montpied [Clermont-Ferrand]
19 Centre Hospitalier Le Mans (CH Le Mans)
20 CHU Nîmes - Hôpital Universitaire Carémeau [Nîmes]
21 APHM - Assistance Publique - Hôpitaux de Marseille
22 Centre Hospitalier de Lens
23 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
24 HEGP - Hôpital Européen Georges Pompidou [APHP]
25 GEOMAS - Géomécanique, Matériaux et Structures
26 MEPHI - Microbes évolution phylogénie et infections
27 Service Anesthésie et Réanimation [Hôpital Nord - APHM]
28 CHV - Centre Hospitalier de Versailles André Mignot
29 CIC Lille - Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301
30 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
31 CHU Nantes - Centre hospitalier universitaire de Nantes
32 Hôpital Ambroise Paré [AP-HP]
33 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
34 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
35 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
36 CHR Metz-Thionville - Centre hospitalier régional Metz-Thionville
37 Service de Réanimation Médicale (CHU de Dijon)
38 Hôpital Louis Mourier - AP-HP [Colombes]
39 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
Stéphane Gaudry
- Function : Author
- PersonId : 1125117
David Hajage
- Function : Author
- PersonId : 1003880
- IdHAL : david-hajage
- ORCID : 0000-0002-8475-4090
- IdRef : 144117959
Guillaume Louis
- Function : Author
- PersonId : 776585
- ORCID : 0000-0002-4208-8122
Dimitri Titeca-Beauport
- Function : Author
- PersonId : 1044736
- ORCID : 0000-0003-2514-4193
- IdRef : 182689786
Sébastien Besset
- Function : Author
Alain Combes
- Function : Author
- PersonId : 999809
- ORCID : 0000-0002-6030-3957
- IdRef : 033468192
Adrien Robine
- Function : Author
Christophe Vinsonneau
- Function : Author
Eric Boulet
- Function : Author
Karim Lakhal
- Function : Author
- PersonId : 1119824
S. Grange
- Function : Author
- PersonId : 18316
- IdHAL : stephane-grange
- ORCID : 0000-0002-7766-0483
- IdRef : 137492464
Marc Leone
- Function : Author
- PersonId : 928586
Saad Nseir
- Function : Author
- PersonId : 910837
- ORCID : 0000-0002-7618-0357
- IdRef : 103027351
Kada Klouche
- Function : Author
- PersonId : 930999
- ORCID : 0000-0003-1633-7700
Jean Reignier
- Function : Author
- PersonId : 928690
- ORCID : 0000-0002-3768-3496
Jean-Damien Ricard
- Function : Author
- PersonId : 918542
Jean-Pierre Quenot
- Function : Author
- PersonId : 998462
- ORCID : 0000-0003-2351-682X
- IdRef : 079287654
Abstract
BACKGROUND: Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy. METHODS: This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed. FINDINGS: Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0-25) in the delayed strategy and 10 days (IQR 0-24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09-2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups. INTERPRETATION: In severe acute kidney injury patients with oliguria for more than 72 h or blood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm. FUNDING: Programme Hospitalier de Recherche Clinique.
Domains
Life Sciences [q-bio]
Origin : Files produced by the author(s)