REMERCIEMENTS Aux membres du jury,

A Monsieur le président du jury, le Professeur Samir Jaber, Pour m'avoir fait l'honneur de présider ce jury de thèse. Pour l'intégration au sein de l'équipe du DAR B lors de mon passage en stage. Pour les messages forts que vous savez faire passer concernant l'importance du sérieux, de la rigueur, de la formation mais aussi du travail en équipe et de la diplomatie. Ils ont marqué mon parcours d'interne et me suivront pour la suite de ma carrière. Je suis heureux de continuer mon cursus au sein de l'équipe du DAR B pour le Docteur Junior. Soyez assuré de mon respect et de ma reconnaissance.

A Monsieur le Professeur Laurent Muller,

Je te remercie d'avoir accepté de participer à mon jury de thèse. J'ai beaucoup appris à tes côtés, que ce soit sur le plan théorique ou sur le plan humain. Je n'oublierai jamais ton soutien dans les moments difficiles qui peuvent émailler une carrière d'anesthésiste-réanimateur. Sois assuré de mon admiration. J'espère pouvoir à nouveau profiter de tes enseignements au cours d'un nouveau passage à Nîmes en tant que docteur Junior.

A Madame la Professeur Claire Roger,

Je suis flatté que tu aies accepté de siéger dans ce jury. Si certaines subtilités de l'infectiologie en réanimation me restent pour le moment inaccessibles, j'ai beaucoup appris à tes côtés. Je n'oublierai pas les messages de curiosité, d'humilité (« nous sommes tous l'orthopédiste de quelqu'un ») et de bienveillance que tu as su faire passer. J'en resterai empreint pour la suite de mon parcours. Merci pour tout.

A mon directeur de thèse, le docteur Clément Monet D'abord pour ta gentillesse, ta rigueur, ta pédagogie et ta bonne humeur en tant que chef de clinique lors de ce stage au DAR B. Ensuite pour avoir accepté de diriger cette thèse, malgré un emploi du temps bien chargé de jeune médecin-père de famille.

Merci pour tes conseils, ta motivation et ton soutien tout au long de ce travail. Ce fut pour ma part un réel plaisir. Cette thèse était le début d'un projet qui s'annonce passionnant, que j'espère poursuivre à tes côtés au cours des prochains mois.

A la famille, Maman, merci pour ton soutien indéfectible au cours de ces (bientôt) 30 années dans les moments de doutes comme dans les certitudes. Merci pour ta joie de vivre, ta tolérance, ta folie, ta douceur. Merci pour toutes ces choses qui m'ont permis d'arriver là où je suis aujourd'hui. J'espère continuer à partager des moments privilégiés avec toi. Je t'aime. Papa, notre relation est fondée sur une pudeur bien masculine et je l'aime comme telle. J'aime ton humour décalé, ton côté bledard complètement assumé. J'admire ta pensée libre, ton goût de découvrir, ta soif de rencontres. Merci pour ton calme, ton soutien, et tout ce que tu m'as inculqué. A Siham, t'avoir comme soeur est une de mes plus grandes fiertés. Je t'observe discrètement, de loin mais je t'ai vu t'épanouir pour devenir une jeune femme intelligente et drôle, dynamique et voyageuse, toujours curieuse, franche, affirmée mais aussi d'une grande douceur. Chaque moment partagé avec toi est un privilège que je chéris. Je te le dis peu, mais je t'aime frangine. A Steph, ma marraine, merci d'avoir été à mes côtés tout au long de ce parcours. Merci pour tes petits gestes A Pierre, une amitié et une rencontre qui changent une vie ! Pour les soirées à refaire le monde jusqu'au petit matin, pour ces longs étés à faire la fête, pour tes plans tchatche foireux. Parce que tu es le seul mec avec qui je trouve ça normal de chanter une chanson qui s'appelle « les hommes que j'aime ». Je le sais, un jour on arrivera à voyager ensemble.

Aux colocs du Yacht : à Sarah, toujours la première dans les ragots mais parce que tu es toujours attentive à ceux qui t'entourent. On a réussi à faire 3h de route seuls tous les deux, c'est la preuve d'une belle amitié. A Marine, du tutorat de biochimie à la coloc' ensemble, tu as toujours été un rayon de soleil, toujours dans le positif, talentueuse dans le choix de tes déguisements, merci pour tous ces fous rires. A Charles, tant de délires avec toi et ton frère Alfred, votre exil à Clermont n'a en rien entaché notre amitié. J'admire ton talent de chanteur (ton tube « Et jour, et nuit » fera un carton) et ton désir de liberté, même si celui-ci te pousse souvent à tomber le pantalon. A Vass, pour cette belle amitié marquée par une carrière dans le BTP avortée (de la tractopelle à la grue de chantier, on avait pourtant bien commencé), des « pour combien » foireux (promis, un jour je te l'achèterai) et des voyages plus ou moins improvisés (Berlin, Martinique, Açores, à quand la suite ?). A Clem, parce que recadrer Vass ne doit pas être de tout repos, parce que j'admire ta vocation à soigner des crevettes. A PB, une belle rencontre pendant cette colloc' ! J'apprécie tout autant ta gentillesse et nos longues discussions sur les grands sujets de la vie, que tes blagues graveleuses et ton intérêt restreint pour les poissons. A Mémé, pour te comporter en maman, pour chercher à apaiser toutes les tensions, pour tes analyses psychiatriques fines. A Dorian, de supérieur hiérarchique au sein du tutorat à ami dévoué, un sacré chemin parcouru. Epicurien, fêtard professionnel, acteur de théâtre, tu es un homme aux multiples facettes. Évite de brûler la chandelle par les deux bouts, qu'on puisse profiter longtemps.

A Maxime, pour ton soutien pas très objectif mais indéfectible. Pour tes blagues pourries. Pour ton égo (un poil) surdimensionné. Pour tes goûts musicaux discutables (Kyo et Manau c'est dépassé). Va savoir pourquoi, t'avoir comme ami est un honneur.

Aux rencontres de P1 : JB, ton côté paternel nous a tous sortis de quelques mauvais pas, tes conseils ont été précieux. A Olivier. Aux copains dentistes, que je vois top peu. Parce que vous êtes les seuls types que je connais qui se sont fait des colliers avec les dents de leurs patients. Vincent, encore un autre « homme que j'aime » ta folie douce et ta joie de vivre nous on fait passer de sacrés beaux moments. A Jordi, pour ta belle mèche lors de nos années lycée, parce que tu es le seul à avoir pu me traîner au CKF et Gab, pour ces parties de caps endiablées.

Aux copains d'externat : Ryadh, une grande sensibilité, une fragilité certaine, une intelligence assumée. L'ensemble masqué par du cynisme. Ça fait de toi un mec louche, mais j'espère que tu te rapprocheras du Sud, qu'on puisse se voir plus souvent. A Samir, tout aussi louche que ton frère, j'ai toujours apprécié les soirées avec toi. A Ted, un faluchage commun avorté (et j'en suis heureux), une montagne de punchlines, quelques soirées. Tu as marqué mon externat. La vie marseillaise te va très bien, j'espère te voir plus souvent. A Bapti, un copain de la première heure.

Des longues soirées d'été sur ta terrasse aux randonnées dans la jungle

Guatémaltèque, on aura vécu quelques aventures. Tu as signalé qu'on se voit trop peu, c'est vrai. Je te ferai cependant remarquer que tes hypoglycémies rendent de toute façon notre communication difficile lors de ces (trop) rares moments. A Clara, merci pour toutes tes qualités : infirmière d'endocrinologie malgré toi, sportive semiprofessionnelle (quel sprint dans ce bus au Guatemala !), brillante gestionnaire d'agence matrimoniale. Tu as grandi et prit de l'assurance, tu resteras toujours ma « pequeñita » préférée. A RomHuc et Paulinette, rencontrés lors d'un master 1 de génétique médicale (quelle idée ?), exilés à Dijon, vous voir est toujours un plaisir. A Jex, le meilleur espion américain que je connaisse, je garderai longtemps des souvenirs de cette expédition en Amérique centrale avec toi. A Anne Lise, merci pour ton humour décalé, ta gentillesse. Tu resteras à jamais mon premier binôme de plongée.

Aux membres du Country Club. Benoît, depuis ce fameux weekend où nous nous sommes auto-proclamés PF, bien du temps a passé. Parfois co-externes, binômes de sous colle l'espace d'un an, futurs collègues de travail, quel chemin nous avons parcouru ensemble ! J'ai de la chance de t'avoir pour ami. A Mathilde, malgré ton accent étrange, j'ai apprécié ta gentillesse, ton humour, et le fait que tu aies accepté Benoit tel qu'il est (on sait que c'est difficile). Tu es une vraie belle rencontre. PS : la concurrence est rude, mais j'espère vous avoir convaincu que je ferai un bon parrain.

A Axelle, en souvenir de toutes nos soirées bonbons-films. A Gauthier, parce qu'on a essayé de créer un boys-band qui s'appelle les 2be3, encore désolé pour tes costumes. A Yann, j'ai connu ton premier studio à Nîmes, ta maison en Corse, et parce que je l'ai PROMIS (depuis 4 ans) à Laura, je viendrai voir votre appartement à Narbonne. A Hugues, même si tu ne préviens pas quand tu rentres à Montpellier. A Arthé, parce qu'on m'a dit que tu étais « la plus bonne de mes copines », toujours un plaisir de partager une soirée avec toi. A TaïTaï, ton exil dans les Alpes ne doit pas te faire oublier d'où tu viens (tu nous as quand même fait exclure d'une auberge de jeunesse), et à Sabine, parce que je pense que c'est grâce à toi qu'il est plus calme.

A la néphrologie Montpelliéraine. La promo d'origine : Juliette, j'espère que tu m'as pardonné d'avoir changé de spécialité et Amélie, pour notre entraide entre pigeons l'espace de 6 mois, tu feras une super anesth-réa.

INTRODUCTION

L'obésité est une pathologie multifactorielle définie par un excès en tissu adipeux, qui expose le patient à différents risques en matière de santé. En pratique clinique, l'obésité est définie par l'organisation mondiale de la santé (OMS) par un indice de masse corporelle [poids (kg)/taille² (m)] supérieur ou égal à 30 kg/m². La classification proposée sépare les obésités "modérées", "sévères" et "très sévères" [START_REF] Schetz | Obesity in the critically ill: a narrative review[END_REF]. En Europe, selon le dernier rapport de l'OMS, la prévalence de l'obésité a augmenté de 138% chez les adultes, entre 2006 et 2016 [START_REF]Obesity in the WHO European region factsheet[END_REF]. En France, en 2017, la prévalence estimée de l'obésité dans la population adulte était de 21.6% [START_REF]Prevalence of obesity among adults, BMI >= 30[END_REF]. Du fait de l'augmentation de la proportion de patients atteints d'obésité dans la population générale, une augmentation des hospitalisations de ces patients en réanimation est également attendue. Il s'agit là d'un défi de santé publique, car l'obésité, dans la population générale, est associée à une augmentation de la mortalité toutes causes confondues [4].

En termes de morbidité, les pathologies associées à l'obésité sont nombreuses. En fonction du type de distribution (viscérale ou sous-cutanée) de l'excès de tissus adipeux, les risques associés à l'obésité incluent le diabète de type 2, l'hypertension artérielle, les maladies cardiovasculaires, les dyslipidémies, la stéato-hépatite non alcoolique, le syndrome d'apnée obstructive du sommeil, le syndrome d'hypoventilation, la perte de capacité physique et la maladie rénale chronique [START_REF] Schetz | Obesity in the critically ill: a narrative review[END_REF]. L'obésité est un facteur de risque de développer une maladie rénale chronique (MRC) avec une perte de fonction rénale plus rapide, comparée à celle de patients sans obésité [START_REF] Lu | Association of age and BMI with kidney function and mortality: a cohort study[END_REF]. Un indice de masse corporelle (IMC) élevé est également associé à l'apparition d'une protéinurie, d'une baisse de débit de filtration glomérulaire (DFG) et d'une insuffisance rénale chronique terminale [START_REF] Chang | Lifestylerelated factors, obesity, and incident microalbuminuria: the CARDIA (Coronary Artery Risk Development in Young Adults) study[END_REF]. De nombreux mécanismes expliquant les effets de l'obésité ont été évoqués. Premièrement, les effets rénaux de l'obésité semblent persister après ajustement sur différentes pathologies associées à l'obésité, telles que l'hypertension artérielle, l'insulino-résistance ou le diabète de type 2. Cependant, le rôle de ces comorbidités reste une des hypothèses pour expliquer la dégradation de la fonction rénale observée chez ces. Par ailleurs, plusieurs études ont montré une association entre le tissu adipeux viscéral (mesuré par le tour de taille et le rapport tour de taille/tour de hanche) et l'apparition d'une MRC.

Ainsi, pour un niveau d'IMC similaire, un tour de taille plus élevé est associé avec une diminution du DFG, suggérant un rôle délétère du tissu adipeux viscéral [START_REF] Pinto-Sietsma | A central body fat distribution is related to renal function impairment, even in lean subjects[END_REF]. En effet, la graisse viscérale possède une activité endocrine (adiponectine, leptine, etc.) qui conduit à une inflammation chronique à bas bruit, à du stress oxydatif, à une activation du système rénine-angiotensine-aldostérone et à une insulino-résistance [START_REF] Kovesdy | Obesity and kidney disease: Hidden consequences of the epidemic[END_REF]. Ces modifications associées à l'obésité sont à l'origine d'une pathologie décrite comme la "glomérulopathie associée à l'obésité" [START_REF] Vd | Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis[END_REF]. L'augmentation de la perfusion rénale et l'hyperfiltration glomérulaire sont par ailleurs associées à une hyper-pression glomérulaire. Finalement, ces modifications peuvent entraîner des lésions histologiques telles qu'une glomérulomégalie et de la hyalinose segmentaire et focale. L'insuffisance rénale aiguë (IRA) en réanimation, chez des patients non sélectionnés, est fréquente et associée à un mauvais pronostic [START_REF] Hoste | Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study[END_REF]. La mortalité hospitalière associée à l'IRA est élevée et varie, en fonction du degré de sévérité, de 25 à 40% lorsqu'une épuration extra-rénale (EER) est nécessaire [START_REF] Hoste | Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study[END_REF][START_REF] Nisula | Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study[END_REF]. Les études conduites chez des and a logistic regression were used for mortality at day 90. Results. A total of 1772 patients with obesity were included. Among them, 253 (14.3%) patients required RRT, and 1519 (85.7%) patients did not; the mortality rate at day 90 was respectively 50.6 % (95% CI [44.4 %-56.7 %]) and 19.6 % (95% CI [17.6%-21.6%]). The mortality rate at 90 days after ICU admission was significantly higher in the RRT group (p < 0.0001 with log rank test). In a multivariate logistic regression, RRT was independently associated with mortality at day 90 after ICU admission with an odds ratio (OR) of 2.3 (95% CI [1.7-3.2]).

Conclusion.

In a population of patients with obesity, the occurrence of renal replacement therapy during ICU stay was independently associated with mortality at day 90 after ICU admission. This data suggests a lack of evidence in this specific population, and contribute to put forward the necessity of prospective, well conducted trials.

BACKGROUND

Obesity is a multifactorial disease defined by an excess of fat or adipose tissue that leads to an increase in health risks. In clinical practice, obesity is defined by the world health organization (WHO) with a body-mass index (BMI) [weight (kg)/height 2 (m)] greater than or equal to 30 kg/m 2 . It is further classified into "moderate", "severe" and "very severe" obesity according to the BMI [START_REF] Schetz | Obesity in the critically ill: a narrative review[END_REF]. In Europe, according to WHO, obesity prevalence has risen 138% in adults between 2006 and 2016 [START_REF]Obesity in the WHO European region factsheet[END_REF]. In France, in 2017, estimated obesity prevalence is up to 21.6% [START_REF]Prevalence of obesity among adults, BMI >= 30[END_REF]. The number of patients with obesity hospitalized in intensive care unit (ICU) is expected to increase as the proportion of these patients is increasing in the general population. It is a serious public health challenge, as obesity in the general population is associated with higher all-cause mortality [4].

Regarding morbidity, diseases associated with obesity are numerous. Depending on the degree and distribution (visceral versus subcutaneous) of excess adipose tissue the risks of obesity include type 2 diabetes, hypertension, cardiovascular diseases, dyslipidemia, non-alcoholic fatty liver disease, obstructive sleep apnea and hypoventilation syndrome, physical disabilities and chronic kidney disease [START_REF] Schetz | Obesity in the critically ill: a narrative review[END_REF]. Obesity is a risk factor for development of chronic kidney disease (CKD) with a quicker loss of kidney function over time compared to patients without obesity [START_REF] Lu | Association of age and BMI with kidney function and mortality: a cohort study[END_REF]. Higher BMI is also associated with proteinuria, low glomerular filtration rate (GFR) and end-stage renal disease [START_REF] Chang | Lifestylerelated factors, obesity, and incident microalbuminuria: the CARDIA (Coronary Artery Risk Development in Young Adults) study[END_REF]. Many mechanisms underlying the effects of obesity on kidney dysfunction have been discussed.

First, the damages to the kidney seem to be persistent after adjustment for the conditions associated with obesity such as high blood pressure, insulin resistance and type 2 diabetes. However, the role of co-existing comorbidities is still a possible explanation for the kidney damages observed in patients with obesity. Second, several studies have shown an association between visceral adipose tissue measured with waist circumference (WC) and waist-hip ratio (WHR) and CKD. For a similar BMI level, a higher WHR is associated with a diminished GFR, suggesting a deleterious role of visceral adipose tissue [START_REF] Pinto-Sietsma | A central body fat distribution is related to renal function impairment, even in lean subjects[END_REF]. Indeed, visceral adipose tissue has an endocrine activity (adiponectin, leptin, etc.) that leads to low-grade chronic inflammation, oxidative stress, activation of the renin angiotensin aldosterone system and insulin resistance [START_REF] Kovesdy | Obesity and kidney disease: Hidden consequences of the epidemic[END_REF]. These modifications associated with obesity result in what has been described as "obesity-related glomerulopathy" [START_REF] Vd | Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis[END_REF].

Increased renal perfusion and glomerular hyperfiltration are associated with glomerular hypertension [START_REF] Bosma | Obesity and renal hemodynamics[END_REF]. Ultimately these modifications can lead to histologic lesions such as glomerulomegaly and focal or segmental sclerosis.

Acute kidney injury (AKI) in ICU, in unselected patients, is frequent and associated with a poor prognosis [START_REF] Hoste | Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study[END_REF]. In hospital mortality associated with AKI is high, depending on the severity of the kidney injury it ranges from 25% to 40% if renal replacement therapy (RRT) is needed [START_REF] Hoste | Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study[END_REF][START_REF] Nisula | Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study[END_REF]. Studies that focus on AKI in patients with obesity in ICU are scarce. One retrospective cohort study showed a 10% risk [95% CI 1.06-1.24; p<0.001] of more severe AKI associated with each 5 kg/m 2 increase in body mass index (BMI). In this study, obesity showed a protective effect on mortality in patients without AKI, however this protective effect was not found in patients with AKI [START_REF] Danziger | Obesity, Acute Kidney Injury, and Mortality in Critical Illness[END_REF]. Another retrospective cohort study on patients with acute respiratory distress syndrome (ARDS) showed an increase in AKI in patients with obesity (adjusted OR 1.20 per 5 kg/m 2 increase in BMI, [95%CI 1.07-1.33]).

Although no increase in mortality compared to patients without obesity with ARDS [START_REF] Soto | Body mass index and acute kidney injury in the acute respiratory distress syndrome[END_REF].

In a study by Druml et al. on patients with AKI requiring RRT, obesity was associated with an increase in AKI. However, in hospital mortality was lowest in the group of patients with obesity (BMI of ≥ 30 < 35 kg/m 2 ) [START_REF] Druml | Impact of body mass on incidence and prognosis of acute kidney injury requiring renal replacement therapy[END_REF]. Obesity appears to be an independent risk factor for AKI and the higher the BMI the higher the incidence of AKI. It could be explained by the chronic underlying renal lesions associated with obesity described earlier in this text.

Moreover, obesity is a known risk factor for increased intra-abdominal pressure [START_REF] Holodinsky | Risk factors for intra-abdominal hypertension and abdominal compartment syndrome among adult intensive care unit patients: a systematic review and meta-analysis[END_REF][START_REF] Malbrain | Prevalence of intra-abdominal hypertension in critically ill patients: a multicentre epidemiological study[END_REF], which could lead to higher AKI incidence.

To our knowledge, few studies have evaluated the incidence and prognosis of patients with obesity that required RRT in the ICU [START_REF] Kim | The impact of disease severity on paradoxical association between body mass index and mortality in patients with acute kidney injury undergoing continuous renal replacement therapy[END_REF][START_REF] Wang | Higher body mass index is not a protective risk factor for 28-days mortality in critically ill patients with acute kidney injury undergoing continuous renal replacement therapy[END_REF][START_REF] Kim | Body mass index is inversely associated with mortality in patients with acute kidney injury undergoing continuous renal replacement therapy[END_REF]. In these studies, conducted in Asia, obesity was defined as a BMI greater than or equal to 25 kg/m 2 (as defined by the Committee of Clinical Practice Guidelines and Korean Society for the Study of Obesity) which does not reflect obesity in the western population.

The main objective of this study was to compare the 90-day mortality between patients that required RRT and patients that did not require RRT in a population with obesity in the ICU. The secondary objectives were to determine, among the population of patients with obesity in ICU, the incidence of AKI and RRT as well as the risk factors for mortality in the overall population as well as in the RRT group.

MATERIALS AND METHODS

Study design

We conducted a retrospective analysis of prospectively collected data of all patients with obesity consecutively admitted to a mixed medical-surgical adult ICU in a university teaching hospital between June 2009 to May 2022. We obtained approval from the local research ethics committee ("Institutional Review Board") of the Montpellier University Hospital (2019_IRB-MTP_05-25).

Data collection

Patient body weight and height were measured at the time of ICU admission. In accordance with WHO recommendation, patients with a body mass index (BMI) ≥ 30 kg/m 2 were defined as "with obesity". All consecutive admissions of patients with obesity hospitalized during the study period in a medical-surgical ICU were included in the study. Patient data were recorded by the ICU's in house physician and included demographics, anthropometrics, clinical and biological data on hospital admission, as well as the Simplified Acute Physiology Score II (SAPS II), ICU admission diagnosis, category of admission (medical or surgical) and comorbidities. Baseline creatinine was defined either by usual creatinine level, if available, or by creatinine level at ICU admission in the absence of AKI at admission. Creatinine and urine output were recorded on day 1. Diagnosis and staging of acute kidney injury (AKI) were defined according to international guidelines from the Kidney Disease: Improving Global Outcomes (KDIGO) foundation (Supplementary table 1) [START_REF] Khwaja | KDIGO clinical practice guidelines for acute kidney injury[END_REF]. Although it has not been validated in patients with obesity, this classification is the most recent and is widely used in recent studies. AKI at admission was defined based on the data recorded on the day of admission. AKI during ICU stay was defined by the occurrence of AKI in patients who did not have AKI at admission. To define the maximum KDIGO stage, we used the KDIGO criteria and only the worst KDIGO stage during the entire ICU stay was retained. Persistent AKI at discharge was defined by nonreturn to creatinine baseline level in patients who were discharged alive from the ICU. In case of renal replacement therapy, duration (number of days) as well as modality of RRT were collected.

Inclusion and exclusion criteria

All consecutive patients with obesity were included. Exclusion criteria were: 1) endstage renal disease (ESRD) on dialysis, 2) age less than 18 years old.

End points

ICU and hospital mortality rates were obtained using hospital electronic patient records.

The primary endpoint was the mortality rate at 90 days (all-cause mortality). The secondary endpoints were 28-day and 365-day mortality, incidence of AKI, incidence, duration, and modality of RRT.

Statistical analysis

First, a descriptive analysis was performed overall and in patients who required (RRT group) and who did not require RRT (non-RRT group). Quantitative variables were expressed as mean (± standard deviation (SD)) and compared using the Mann-Withney test. Qualitative variables were expressed as numbers (%) and compared using the chisquare test or Fisher test as appropriate. In case of missing values, the number of missing values was clearly stated for each variable, and no replacement method was used (as shown in supplementary appendix). Then, a univariate logistic regression analysis was done according to survival at day 90 in the RRT group and in the non-RRT group. Second, Kaplan-Meier analysis was performed to determine the survival lifetimes for 90-day survival, and a log-rank test was used to compare the two survival curves. Third, a multivariate logistic regression was performed to assess the relationship among RRT status (forced variable), and mortality at day 90 after ICU admission in the overall population. Interactions between variables were tested. demographics, comorbidities, admission characteristics and pre-RRT variables and treatments, associated with outcomes in AKI requiring RRT. These included gender, age, pre-RRT treatments and characteristics (SAPS II, vasopressors, mechanical ventilation). A stepwise procedure (with a threshold of p < 0.05 to stay in the final model) was used to select the final model.

Odds ratios (OR) were provided for each variable included in the multivariate model.

RESULTS

Patient characteristics

Of the 8807 patients admitted to the ICU during the study period, 1804 with obesity were identified, of which 1772 were included. Figure 1 presents the flow chart of the study.

Among the 1772 patients, 253 (14.3%) required RRT (RRT group) and 1519 (85.7%) did not (non-RRT group). Within the non-RRT group, 793 (52.2%) had an AKI during ICU stay and 722 did not (47.8%). The main demographic characteristics of the included patients are detailed in Table 1. No difference in obesity grade was found between the two groups.

Regarding past medical history, patients in the RRT group had a higher rate of chronic kidney disease (14.6% versus 6.2%, p=0.002), diabetes (28.9% versus 21.1%, p=0.009) and cirrhosis (35.6% versus 29.0%, p=0.038). Patients in the RRT group were more severely ill than patients in the non-RRT group, they had a higher SAPS 2 score (54.9 ± 18.6 versus 39.2 ± 17.6, p<.001), and a significantly higher incidence of vasopressors and mechanical ventilation at ICU admission. Serum creatinine at ICU admission in the RRT group was significantly higher (250.0 ± 157.6 µmol/l) than in the non-RRT group (119.2 ± 87.9 µmol/l, p<.001). Urine output during the first 24 hours after ICU admission was significantly lower in the RRT group (1344 ± 1550 ml) than in the non-RRT group (2159 ± 1345 ml, p<.001).

Table 2 presents the main demographic characteristics for survivors and non-survivors, in both groups.

In the RRT group, non-survivors were older (age 60.0 years versus 63.7 years, p=0.013), had a higher proportion of grade 3 obesity (12% versus 21.9%, p=0.044) and were more severely ill as shown by a higher SAPS II score (50.4 versus 59.7, p<0.001) and a higher proportion of patients with vasopressors (65.6% versus 86.7%, p<0.001). In the RRT group, chronic kidney disease was more frequent in survivors than in non-survivors (19.2% versus 10.2%, p=0.05).

In the non-RRT group, non-survivors were older (age 59.3 years versus 65.8 years, p<0.001), had a higher proportion of patients with grade 1 obesity (55.5% versus 61.9%, p=0.042), were more frequently admitted for medical reasons (38.8% versus 71.4%, p<0.001). In the non-RRT group, non-survivors were more severely ill as shown by a higher SAPS II score (35.7 versus 53.6, p<0.001), and higher proportions of patients with vasopressors (41.9% versus 63.6%, p<0.001) and mechanical ventilation at admission (57.7% versus 67.7%, p=0.002). In the non-RRT group, non-survivors had a significantly higher incidence of KDIGO stage 2 (17.9% versus 23.8%, p=0.021) and 3 (8.4% versus 25.8%, p<0.001) AKI compared to survivors. In the non-RRT group, non-survivors had a serum creatinine level at admission significantly higher (107.7 µmol/L versus 167.0 µmol/L, p<0.001) while urine output was significantly lower (2256 mL/24h versus 1764 mL/24h, p<0.001) compared to survivors.

Main endpoint, comparison of 90-day survival according to RRT status

In the RRT group, the mortality rate at day 90 was 50.6 % (95% CI [44.4 %-56.7 %]). In the non-RRT group, the mortality rate at day 90 was 19.6 % (95% CI [17.6%-21.6%]). The probability of survival was significantly different when performing a Kaplan-Meier analysis (p < 0.0001 by log rank test, Figure 2).

Multivariate analysis

After multivariate analysis, in the overall study population, a significant association was found between age (OR 1.02, 95% CI [1.01-1.03]), history of cirrhosis (OR 1.6, 95% CI [1.2-available for 20 (7.9 %) patients. The mean duration of RRT was 8 ± 8.8 days, data were missing for 32 (12.6%) patients. In the RRT group, survivors had a longer RRT duration compared to non survivors (9.6 ± 1.3 days versus 6.6 ± 6.7 days, respectively, p=0.002).

Data for modality and duration of RRT are shown in Supplementary Appendix table 4.

DISCUSSION

The primary outcome of this study was mortality at day 90, which was statistically different in RRT and non-RRT patients. This association was confirmed after multivariate logistic regression, showing that RRT was independently associated with mortality in this population. To our knowledge, this is the first study that seeks to assess the relationship between renal replacement therapy and mortality at day 90 after ICU admission, in a population of patients with obesity.

Mortality and association with RRT

Two large prospective cohorts conducted in unselected patients aimed to describe the epidemiology of AKI and RRT in ICU patients [START_REF] Hoste | Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study[END_REF][START_REF] Nisula | Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study[END_REF]. In these studies, the percentage of patients who underwent RRT varied from 10 to 15%, and mortality amongst RRT patients was around 40%. In our study, the incidence of patients with obesity in ICU who underwent RRT was 14.3%, which is similar to the incidence of RRT in the general population in ICU. However, with 50.6% at 90 days after ICU admission, we found a slightly higher mortality rate in the RRT group than previously described in large cohorts of patients without obesity. Furthermore, our results support an independent effect of RRT on mortality. In fact, after a multivariate analysis, the OR for mortality at 90 days after ICU admission was 2.3, 95% CI [1.7-3.2]. In unselected patients, studies on the impact of RRT on mortality yielded conflicting results. In a prospective cohort comparing conservative treatment and RRT, Elseviers et al. found that RRT was associated with higher hospital mortality in a multivariate logistic regression [START_REF] Elseviers | Renal replacement therapy is an independent risk factor for mortality in critically ill patients with acute kidney injury[END_REF]. On the contrary, Clec'h et al reported similar rates of mortality in RRT and non-RRT patients in a retrospective study after propensity matched analysis [START_REF] Clec'h C, Darmon | Efficacy of renal replacement therapy in critically ill patients: a propensity analysis[END_REF]. These results were concordant with a retrospective interrogation of the BEST Kidney data conducted by Bagshaw et al [START_REF] Bagshaw | Association between renal replacement therapy in critically ill patients with severe acute kidney injury and mortality[END_REF]. In a retrospective analysis, Liborio et al. even found that RRT was associated with a better hospital survival when prescribed for metabolic acidosis, hyperkalemia, high azotemia (defined by serum blood urea > 60 mg/dL) or a cumulative fluid balance > 5% of the body weight [START_REF] Libório | AKI complications in critically ill patients: association with mortality rates and RRT[END_REF].

RRT and obesity in the ICU

Although there is a great number of studies about ICU life support, few of them are about RRT in patients with obesity. Furthermore, to our knowledge, while several studies investigated the effect on BMI on the risk of AKI and morality [START_REF] Danziger | Obesity, Acute Kidney Injury, and Mortality in Critical Illness[END_REF][START_REF] Soto | Body mass index and acute kidney injury in the acute respiratory distress syndrome[END_REF][START_REF] Druml | Impact of body mass on incidence and prognosis of acute kidney injury requiring renal replacement therapy[END_REF][START_REF] Kim | The impact of disease severity on paradoxical association between body mass index and mortality in patients with acute kidney injury undergoing continuous renal replacement therapy[END_REF][START_REF] Wang | Higher body mass index is not a protective risk factor for 28-days mortality in critically ill patients with acute kidney injury undergoing continuous renal replacement therapy[END_REF][START_REF] Kim | Body mass index is inversely associated with mortality in patients with acute kidney injury undergoing continuous renal replacement therapy[END_REF], there is currently no data available exploring the effect of RRT on outcomes in patients with obesity in the ICU. Druml et al. published a retrospective analysis from a database of 53 Austrian ICUs [START_REF] Druml | Impact of body mass on incidence and prognosis of acute kidney injury requiring renal replacement therapy[END_REF]. The aim of the study was to assess the impact of BMI on outcomes of patients undergoing RRT for AKI. A total of 79 576 patients were included. In the overall population, a higher BMI was associated with a higher risk of developing an AKI, with a maximum risk for the sub-group of patients with a BMI ≥ 35 kg/m². In the entire cohort, 5232 patients were part of the "AKI cohort" (i.e patients on dialysis for AKI) and amongst them, 1130 patients were with obesity. The ICU mortality rate of the AKI cohort was 49.4 % and the hospital mortality rate was 57%. After a multivariate analysis, the authors showed a U-shaped pattern mortality curve. The highest mortality was for the underweight group and the group of patients with obesity and a BMI ≥ 35 kg/m², while the lowest was for the group of patients with obesity but with a BMI ≥ 30 and < 35 kg/m². However, the authors did not explore the effect of RRT on survival. In addition, three studies on the impact of BMI on mortality of patients undergoing RRT were carried out in Asian countries [START_REF] Kim | The impact of disease severity on paradoxical association between body mass index and mortality in patients with acute kidney injury undergoing continuous renal replacement therapy[END_REF][START_REF] Wang | Higher body mass index is not a protective risk factor for 28-days mortality in critically ill patients with acute kidney injury undergoing continuous renal replacement therapy[END_REF][START_REF] Kim | Body mass index is inversely associated with mortality in patients with acute kidney injury undergoing continuous renal replacement therapy[END_REF]. The results are contradictory. And, while adapted to the population of the study, does not seem applicable to a western population. Moreover, none of these studies explored a possible independent effect of RRT on survival.

Association between chronic kidney disease and mortality

Another finding of our multivariate analysis is that medical admission was consistently associated with mortality with odds ratios of 2.7 (95% CI [2.1-3.5]), 2.9 (95% CI [2.2-3.9]) and 2.003 (95% CI [1.1-3.5]) in the overall cohort, non-RRT group and RRT group, respectively. This data is consistent with a previous retrospective analysis conducted in our center [START_REF] Jong | Medical Versus Surgical ICU Obese Patient Outcome: A Propensity-Matched Analysis to Resolve Clinical Trial Controversies[END_REF]. In the RRT group, a history of chronic kidney disease was a protective factor for mortality at day 90, with an odds ratio of 0.3 (95% CI [0.2-0.8]). There are few studies on non-dialysis chronic kidney disease patients undergoing RRT for AKI in the ICU.

One study has shown that pre-existing CKD was associated with a better survival rate at 1 year and less major adverse kidney events (i.e a composite criterion of death, ESRD needing dialysis, and incomplete kidney recovery) at 1 year, in patients undergoing RRT. This finding did not persist after multivariate analysis [START_REF] De Corte | Long-term outcome in ICU patients with acute kidney injury treated with renal replacement therapy: a prospective cohort study[END_REF]. In two other studies, in a general ICU population, CKD was associated with a higher risk of AKI and a worse survival rate [START_REF] Lebiedz | Impact of preexisting chronic kidney disease on acute and long-term outcome of critically ill patients on a medical intensive care unit[END_REF][START_REF] Rimes-Stigare | Longterm mortality and risk factors for development of end-stage renal disease in critically ill patients with and without chronic kidney disease[END_REF]. This result should be taken with caution due to the small number of CKD patients in the RRT group. Therefore, we cannot exclude that it is caused by unmeasured confounders.

AKI requiring RRT in cirrhosis patients

In our population, almost one third of the patients had a history of liver cirrhosis. In this sub-group, AKI requiring RRT is associated with a dramatic prognosis which is largely dependent on the eligibility for transplantation. In a prospective cohort of 193 critically ill cirrhotic patients, 40% underwent RRT, in these patients 90-day mortality was as high as 91% [START_REF] Staufer | Renal replacement therapy in critically ill liver cirrhotic patients-outcome and clinical implications[END_REF]. A retrospective cohort of 138 patients admitted in a French ICU, found an inhospital survival rate of 31% in patients requiring RRT [START_REF] Das | Cirrhotic patients in the medical intensive care unit: Early prognosis and long-term survival*[END_REF]. In fact, in our multivariate analysis, cirrhosis was independently associated with mortality in the overall cohort with an OR of 1.6 (95% CI [1.2-2.1]). But this finding persisted only in the non-RRT sub-group, with an OR of 1.6, 95% CI [1. 1-2.1]). This might be explained by a "bridge to transplantation" strategy toward RRT, where only patients eligible to transplantation would undergo RRT. Whereas, in patients not eligible to transplantation, RRT might be considered futile. The difference in these two groups has been illustrated in a recent retrospective cohort, the mortality rate ranged from 40% at 6 months for patients eligible to transplant, to 85% for patients not listed for transplantation [START_REF] Allegretti | Prognosis of Patients with Cirrhosis and AKI Who Initiate RRT[END_REF].

Vascular accesses in patients with obesity in the ICU

The technical aspects of RRT in a population with obesity can be challenging. A post hoc analysis of four randomized trials gathered a large database on vascular accesses in patients with obesity [START_REF] Buetti | Obesity and risk of catheter-related infections in the ICU. A post hoc analysis of four large randomized controlled trials[END_REF]. In this study, patients with BMI ≥ 40 kg/m² had an increased risk of intravascular catheter infection. Furthermore, the highest hazard ratios (HR) were observed for dialysis catheter either inserted in the femoral vein (HR 10.95, 95% CI 2.75-43.67, p = 0.0007) or in the jugular vein (HR 10.73, 95% CI 2.58-44.66, p = 0.0011). Of note, patients with a BMI ≥ 40 kg/m² had a higher rate of mechanical complications relative to catheter insertion, when compared to patients with a BMI < 40 kg/m² (13.5% versus 9.6%, respectively). This result was not statistically significant (p=0.22). Although our study was not designed to assess such outcomes it could be an issue faced when taking care of patients with obesity in the ICU that require RRT with potential consequences on patients-centered outcomes.

RRT dose and obesity

While taking care of any ICU patient, weight is a crucial information. For example, drugs dose, diagnosis of AKI, or its treatment by RRT require this information. According to the KDIGO classification [START_REF] Khwaja | KDIGO clinical practice guidelines for acute kidney injury[END_REF], urine output shall be expressed in mL/kg/h, hence posing a risk of false positive diagnosis of AKI in patients with obesity. Whether it would be useful to measure urine output (ml/kg/h) using lean body weight or ideal body weight instead of real body weight has never been studied. However, the creatinine criterion is less susceptible to this bias, hence limiting the confusion. Moreover, improvement in prognosis of RRT patients was made by determining the adequate dialysis dose, which is largely dependent on the patient's weight. For example, when using CRRT, the dose is expressed in mL/kg/h. To be precise, it is the volume of effluent (i.e convective volume in case of hemofiltration, diffusive volume in case of hemodialysis, or the sum of both in case of hemodiafiltration) according to the weight of the patient and time. After three large randomized controlled trials [START_REF] Ronco | Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial[END_REF][START_REF]Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury[END_REF][START_REF]Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients[END_REF], the KDIGO guidelines recommend a target dose of 20 to 25 mL/kg/h [START_REF] Khwaja | KDIGO clinical practice guidelines for acute kidney injury[END_REF]. To calculate the dosing of RRT, the study by Ronco et al. used body weight before admission in the ICU, the VA-NIH trial used body weight before the onset of acute illness and the RENAL trial used body weight at the time of randomization. Although it is not specified, we can assume that total body weight was used, because these studies were conducted in unselected patients. As for IHD, the KDIGO guidelines recommend that the dosing was based on the Kt/V index, in which K is the urea clearance of the dialyzer, t is the duration of dialysis, and V is the volume of distribution of urea (dependent of height, weight, gender and age) [START_REF] Khwaja | KDIGO clinical practice guidelines for acute kidney injury[END_REF]. While this formula was described in the first place for chronic dialysis, a Kt/V of 3.9 is recommended in the AKI setting. This cut off is derived from two randomized, controlled trials [START_REF]Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury[END_REF][START_REF] Schiffl | Daily Hemodialysis and the Outcome of Acute Renal Failure[END_REF]. Once again, the weight of the patient is necessary to calculate the appropriate dosing, as it is the main factor to estimate the volume of distribution of urea.

In the outpatient dialysis setting a BMI ≥ 35 kg/m² seems to confer a survival advantage in this population, being part of what have been called the "obesity paradox" [START_REF] Leavey | Body mass index and mortality in « healthier » as compared with « sicker » haemodialysis patients: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS)[END_REF][START_REF] Diwan | Impact of obesity on dialysis and transplantand its management[END_REF].

Yet, dialysis adequacy in patients with obesity is still subject to debate. One part of the nephrologists tends to increase dialysis dose according to an augmentation of urea distribution volume, mainly by increasing session time and/or frequency [START_REF] Turgut | Challenges Associated with Managing End-Stage Renal Disease in Extremely Morbid Obese Patients: Case Series and Literature Review[END_REF][START_REF] Celebi-Onder | Treating the Obese Dialysis Patient: Challenges and Paradoxes: TREATING THE OBESE DIALYSIS PATIENT[END_REF]. On the contrary, because urea's diffusion in fat tissues seems to be limited, the other part argues that a calculation of the dose based on total body weight can lead to a relative increase in dialysis dose in patients with obesity thus explaining the advantage in survival [START_REF] Davenport | Differences in prescribed Kt/V and delivered haemodialysis dose-why obesity makes a difference to survival for haemodialysis patients when using a « one size fits all » Kt/V target[END_REF].

There is currently no data available on RRT doses in patients with obesity in the ICU, and they were not available in our study. However, we might hypothesize that one part of the mortality excess can be attributed to an inadequate dialysis dose. Two antagonist hypotheses can be made. On one hand, one could argue that the dialysis dose should be increased in patients with obesity hence using at least the total body weight as a base for the calculation. On the other hand, one could argue that using lean body weight or adjusted body over total body weight to determine the RRT dose could be sufficient, hence permitting to save human and material resources.

Study limitations

Our study bears several limitations. First, the retrospective, monocentric uncontrolled design of the study is intrinsically subject to biases. We tried to limit this effect by using a standardized prospective ICU software-based recording. Second, even though weight was determined on the day of admission, we cannot exclude that fluid overload may have affected BMI. Third, the absence of a control group of patients without obesity can limit the external validity of the study. However, data on the general ICU population are numerous, allowing comparison with previous studies. Fourth, lacking data regarding urine output, dialysis dose and specific complications of RRT (mechanical complications of catheters, catheter related infections, bleedings) could have biased the results of our study.

CONCLUSION

  attentionnés. Aux cousin(e)s Clara, Quentin et Rose, à Nadia, Marwan et Jibril, aux tontons Marco et Franck, nous nous voyons trop peu, mais chaque moment partagé me rappelle l'importance de la famille. Aux Bretons, Jacquie et Maurice, Jean Marie, Marie Claude, Tiffenn et Cloë, tous ces étés passés à vos côtés font partie de mes plus beaux souvenirs d'enfance. A Anne Marie pour nos petits joggings sur l'Ile Grande. A Lucie, bien que mon QI artistique s'approche de zéro, je suis admiratif de ton parcours, chaque moment partagé avec toi est un plaisir. A Marion. A Julian, Martine Alexis et Dominique, pour tous ces étés ensemble, à jouer au basket ou au poker. A Thierry. Aux grands parents, en espérant que vous auriez été fiers. A la belle famille, Danièle et Guy pour m'avoir accueilli avec tant de bienveillance, à Alexandre pour m'avoir rappelé que mes amis ont des goûts musicaux discutables, à Camille pour ta gentillesse lors de mon arrivée chez les Ogier. A Galaad et Dimitri.

  FIGURES ............................................................................................................................... SUPPLEMENTARY APPENDIX ................................................................................................

  patients atteints d'obésité présentant une IRA en réanimation sont rares. Une cohorte rétrospective retrouvait que, pour chaque augmentation de l'IMC de 5 kg/m², il existait une augmentation de 10% du risque d'IRA [95% IC 1.06-1.24 ; p<0.001]. Dans cette étude, l'obésité présentait également un effet protecteur sur la mortalité des patients sans IRA, qui n'était pas retrouvé chez les patients présentant une IRA[START_REF] Danziger | Obesity, Acute Kidney Injury, and Mortality in Critical Illness[END_REF]. Une autre cohorte rétrospective chez des patients en syndrome de détresse respiratoire aiguë retrouvait une augmentation du risque d'IRA chez les patients avec obésité (OR ajusté 1.20 pour 5 kg/m 2 d'augmentation d'IMC, [95% IC 1.07-1.33]). La mortalité était cependant similaire à celle des patients sans obésité[START_REF] Soto | Body mass index and acute kidney injury in the acute respiratory distress syndrome[END_REF]. Dans une autre étude réalisée par Druml et col. dans une population de patients avec une IRA nécessitant une EER, l'obésité était associée avec une augmentation de l'incidence de l'IRA. Cependant, la mortalité hospitalière était la moins importante dans le groupe de patients avec obésité modérée (IMC ≥ 30 < 35 kg/m 2 ) [15]. L'obésité semble donc être d'une part un facteur de risque indépendant d'IRA, d'autre part, il semble exister une relation linéaire entre l'IMC et le l'incidence d'IRA (plus l'IMC augmente, plus l'incidence d'IRA augmente). Les lésions rénales chroniques présentées plus tôt dans cette introduction, peuvent participer à expliquer ce phénomène. De plus, l'obésité est un facteur de risque reconnu d'augmentation de la pression intra-abdominale [16, 17], qui pourrait contribuer à l'augmentation de l'incidence de l'IRA. A notre connaissance, peu d'études ont évalué l'incidence et le pronostic de patients atteints d'obésité et nécessitant une épuration extra-rénale en réanimation [18-20]. Dans ces études, réalisées en Asie, l'obésité était définie par un IMC supérieur ou égale à 25 kg/m² (comme défini par le "Committee of Clinical Practice Guidelines and Korean Society for the Study of Obesity"). L'objectif principal de cette étude était de comparer la mortalité à 90 jours après l'admission en réanimation, chez les patients ayant nécessité une EER comparé aux patients n'ayant pas nécessité d'EER, dans une population de patients atteints d'obésité. Les objectifs secondaires étaient de déterminer, dans cette même population, l'incidence et l'IRA et de l'EER, ainsi que les facteurs de risques de mortalité dans l'ensemble de la population d'étude et dans le groupe EER. ARTICLE Incidence, short and long term outcomes of renal replacement therapy in critically ill patients with obesity : a single center retrospective study of 1772 cases ABSTRACT Background. In patients with obesity, data on the outcomes associated with renal replacement therapy are scarce. The main objective of this study was to compare the 90day mortality between patients who required renal replacement therapy (RRT) and patients who did not require RRT in a population with obesity in the ICU. Material and methods. We conducted a retrospective, single-center study. The data were prospectively collected from June 2009 to May 2022. We included all patients with obesity (defined by body mass index ≥ 30 kg/m2) admitted in a mixed medical-surgical adult ICU in France. Urine output (UO) in the first 24 hours after admission and serum creatinine (SCr) were assessed at admission and daily, hence permitting to stage the severity of acute kidney injury according to the KDIGO classification. The RRT-status was assessed during the entire ICU stay, based on medical records. A Kaplan-Meier analysis

  Statistical significance was considered at p < 0.05; p values were two-tailed. The statistical analysis was performed by the Medical Statistical Department of the Montpellier University Hospital with the help of statistical software (SAS, version 9.4; SAS Institute; Cary, NC).

FIGURESFigure 1 .Figure 2 .

 12 FIGURES

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  a une bière à boire ensemble. Fabien, je suis sûr que tu y es pour quelques chose dans mon attrait pour la réanimation. Cédric, un des médecins les plus drôles et les plus compétents que j'ai pu côtoyer, avec Camille vous faites de supers parents.

	A Romain, ta force tranquille et ta bienveillance me laissent admiratif. Partager un moment avec toi est toujours un plaisir parce que, oui, l'amitié entre anesthésistes et orthopédistes est possible ! Aux copains de Perpignan : Lilia moitié princesse, moitié bonhomme, tu m'auras auront conduits à quelques fous rire. beaucoup fait rire. Benjamin, l'autoproclamé roi des cathéters, tes côtés inadapté et misanthrope A la fratrie Debourdeau :

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Table 1 .

 1 This retrospective cohort of 1772 patients with obesity highlights the relationship between renal replacement therapy and mortality at day 90 after ICU admission. The crude mortality rate at day 90, was 50.6 % (95% CI [44.4 %-56.7 %]) and 19.6 % (95% CI [17.6%-21.6%]) (p < 0.0001) in the RRT and non-RRT group, respectively. After a multivariate analysis, we described for the first time an independent association between RRT and long-term mortality (OR 2.3, 95% CI [1.7-3.2]) in this specific population. Large randomized, controlled trials comparing the effects of RRT dose, modalities and specific complications in patients with obesity are further needed. Patients' characteristics in patients who required RRT and patients who did not Values given as mean ± SD or number (%) BMI body mass index, SAPS simplified acute physiology score, ICU intensive care unit, LOS length of stay, KDIGO Kidney Disease: Improving Global Outcomes

	TABLES
	Patients' characteristics	Overall (n= 1772)	RRT group (n= 253)	Non-RRT group (n= 1519)	p value
	Age, years	60.7 ± 13.6	61.7 ± 12.1	60.5 ± 13.8 0.193
	Female gender	682 (38.5)	81 (32.0)	601 (39.6) 0.025
	Size, cm	169 ± 9.5	169.7 ± 9.2	168.9 ± 9.6 0.146
	Weight, kg	105.5 ± 26.3	104.6 ± 24.6	105.7 ± 26.5 0.697
	Body mass index, kg/m²	36.9 ± 8.8	36.4 ± 9.3	37.0 ± 8.7 0.329
	Obesity grade
	Grade 1	997 (56.3)	141 (55.7)	856 (56.4) 0.891
	Grade 2	419 (23.7)	69 (27.3)	350 (23.0) 0.150
	Grade 3	356 (20.1)	43 (17.0)	313 (20.6) 0.204
	Past medical history
	Chronic kidney disease	162 (9.1)	37 (14.6)	126 (8.2) 0.002
	Congestive heart failure	149 (8.4)	23 (9.1)	126 (8.3) 0.673
	Hypertension	600 (33.9)	91 (36.0)	509 (33.5) 0.473
	Diabetes	393 (22.2)	73 (28.9)	321 (21.1) 0.009
	Chronic pulmonary disease	307 (17.3)	36 (14.2)	271 (17.8) 0.178
	Cirrhosis	530 (29.9)	90 (35.6)	441 (29.0) 0.038
	Reason for ICU admission
	Medical	846 (47.3)	159 (62.9)	687 (45.2) <.001
	Surgical	926 (52.3)	94 (37.2)	833 (54.8) <.001
	SAPS II	41.4 ± 18.6	54.9 ± 18.6	39.2 ± 17.6 <.001
	Vasopressors at ICU admission	798 (45)	193 (76.3)	605 (39.8) <.001
	Mechanical ventilation at ICU admission	1205 (68)	206 (81.4)	1000 (65.8) <.001
	ICU LOS, days	10.3 ± 25.7	23.7 ± 30.1	8.1 ± 24.2 <.001
	Serum creatinine at ICU admission, µmol/L	137.9 ± 110.7 250.0 ± 157.6	119.2 ± 87.9 <.001
	Urine output during first 24 hours after ICU admission, mL	2035 ±1408	1344 ± 1550	2159 ± 1345 <.001
	Max KDIGO stage during ICU stay
	No AKI	724 (41)	0	724 (48) <.001
	1	326 (18)	0	326 (21) <.001
	2	289 (16)	0	289 (19) <.001
	3	433 (25)	253 (100)	180 (12) <.001

Table 2 .

 2 Patients' characteristics in survivors and non-survivors according to the RRT statusValues given as mean ± SD or number (%) BMI body mass index, SAPS simplified acute physiology score, ICU intensive care unit, LOS length of stay, KDIGO Kidney Disease: Improving Global Outcomes

			RRT group (n= 253)		Non-RRT group (n= 1519)
	Patients' characteristics	Survivors	Non survivors	p value	Survivors	Non survivors	p value
		(n= 125)	(n= 128)		(n= 1221)	(n= 298)
	Age, years	60.0 ± 13.5	63.7 ± 10.3	0.013 59.3 ± 13.9	65.8 ± 12.4	<.001
	Female gender	44 (54.3)	37 (45.7)	0.346 485 (39.7)	112 (37.6)	0.642
	Size, cm	170.3 ± 9.5	169.1 ± 8.9	0.471 169.0 ± 9.6	168.2 ± 9.6	0.238
	Weight, kg	104.3 ± 24.5	104.9 + 24.8	0.575 106.4 ± 26.9	102.6 ± 24.7	0.019
	Body mass index, kg/m²	36.0 ± 8.3	36.8 ± 10.2	0.531 37.2 ± 8.8	36.3 ± 8.5	0.020
	Obesity grade
	Grade 1	72 (57.6)	69 (53.9)	0.613 673 (55.5)	183 (61.9)	0.042
	Grade 2	38 (30.4)	31 (24.2)	0.323 284 (23.4)	64 (21.4)	0.537
	Grade 3	15 (12)	28 (21.9)	0.044 262 (21.5)	51 (16.7)	0.077
	Past medical history
	Chronic kidney disease 24 (19.2)	13 (10.2)	0.050 91 (11.9)	35 (7.5)	0.018
	Congestive heart failure	10 (8.0)	13 (10.2)	0.663 92 (7.5)	34 (11.6)	0.033
	Hypertension	42 (33.6)	49 (38.3)	0.513 405 (33.2)	103 (35.0)	0.582
	Diabetes	37 (29.6)	36 (28.1)	0.890 258 (21.2)	63 (21.4)	0.937
	Chronic pulmonary disease	14 (11.2)	22 (17.2)	0.209 217 (17.8)	54 (18.4)	0.800
	Cirrhosis	39 (31.2)	51 (39.8)	0.189 329 (27.0)	112 (38.1)	0.001
	Reason for ICU admission
	Medical	54 (56.8)	88 (68.8)	0.052 474 (38.8)	212 (71.4)	<.001
	Surgical	71 (43.2)	40 (31.2)	0.070 747 (61.2)	86 (28.6)	<.001
	SAPS II	50.4 ± 17.5	59.2 ± 19.4	<.001 35.7 ± 15.1	53.6 ± 19.7	<.001
	Vasopressors at ICU admission 82 (65.6)	111 (86.7)	<.001 511 (41.9)	187 (63.6)	<.001
	Mechanical ventilation at ICU admission	99 (79.2)	107 (83.6)	0.420 704 (57.7)	199 (67.7)	0.002
	ICU LOS, days	31.3 ± 34.3	21.7 ± 31.8	<.001 8.0 ± 16.1	6.2 ± 6.6	0.024
	Serum creatinine at ICU admission, µmol/L	255.8 ± 170.2 244.3 ± 144.8	0.868 107.7 ± 74.9	167.0 ± 117.2	<.001
	Urine output during first 24 hours after ICU admission, mL	1402 ± 1575	1276 ± 1522	0.308 2256 ± 1334	1764.4 ± 1322.5 <.001
	Max KDIGO stage during ICU
	stay
	No AKI	0	0	NA	649 (53.1)	75 (24.5)	<.001
	1	0	0	NA	251 (20.6)	75 (24.5)	0.155
	2	0	0	NA	218 (17.9)	71 (23.8)	0.021
	3	125 (100)	128 (100)	NA	103 (8.4)	77 (25.8)	<.001

PREAMBULE

occurrence of RRT (OR 2.3, 95% CI [1.7-3.2]) and death at 90 days after ICU admission.

In the RRT group, age (OR 1.03, 95% CI [1.01-1.06]), history of chronic kidney disease (OR 0.3, 95% CI [0.2-0.8]), SAPS II (OR 1.02, 95% CI [1.01-1.04]) and medical admission (OR 2.0, 95% CI [1.1-3.5]) were independently associated with death at 90 days after ICU admission.

In the non-RRT group, age (OR 1.02, 95% CI [1.01-1.03]), history of cirrhosis (OR 1.6, 95% CI [1.1-2.1]), SAPS II (OR 1.05, 95% CI [1.04-1.06]) and medical admission (OR 2.9, 95% CI [2.2-3.9]) were independently associated with death at 90 days after ICU admission.

Odds ratios for death at 90 days after ICU admission are shown in table 3 and figure 4.

Secondary endpoints

Overall mortality, 28-day and 365-day mortality rate according to RRT status

The overall mortality rate was 17.5% at day 28, 24% at day 90 and 30.3% at day 365.

In the RRT group, mortality rates at day 28 and day 365 were 38.3 % (95% CI [32.3%-44.3%]) and 59.3 % (95% CI [53.2-65.3]), respectively (Figure 3B). In contrast, in the non-RRT group, mortality rates at day 28, and day 365 were 14.1% (95% CI [12.3%-15.8%]) and 25.5 % (95% CI [23.3%-27.7%]), respectively (Figure 3A). When performing a Kaplan-Meier analysis, the difference was statistically significant at day 28 and day 365.

Incidence of AKI, incidence, duration, and modality of RRT

In the overall population of patients with obesity admitted to the ICU (n=1772), 1046 (59 %) suffered from AKI during ICU stay and 253 (14.3%) required RRT. Among the patients with AKI (n=1046), 24.2% required RRT.

In the RRT group, 134 (53%) patients had AKI at admission, and 119 (47%) developed AKI during ICU stay. In the non-RRT group, AKI at admission was present in 285 (18.8%) patients. Furthermore, 509 (33.5%) patients developed AKI during ICU stay. Data on the occurrence of AKI were missing for 4 patients. Data for incidence of AKI are shown in Supplementary Appendix table 3. Regarding RRT modalities, 110 patients (43.5 %) underwent continuous RRT alone, 28 patients (11.1 %) underwent intermittent haemodialysis and 95 (37.5 %) patients underwent both modalities. Data were not ➢ Je donnerai mes soins gratuits à l'indigent et n'exigerai jamais un salaire au-dessus de mon travail.

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