title: Inflammation Modifies the Paradoxical Association between Body Mass Index and Mortality in Hemodialysis Patients.
abstract: High body mass index (BMI) is paradoxically associated with better outcome in hemodialysis (HD) patients. Persistent inflammation commonly features in clinical conditions where the obesity paradox is described. We examined the relationship between BMI and mortality in HD patients, accounting for inflammation, in a historic cohort study of 5904 incident HD patients enrolled in 2007-2009 (312 facilities; 15 European countries) with ≥3 months of follow-up. Patients were classified by presence (n=3231) or absence (n=2673) of inflammation (C-reactive protein ≥10 mg/l and/or albumin ≤35 g/l). Patients were divided into quintiles by BMI (Q1-Q5: <21.5, 21.5-24.0, >24.0-26.4, >26.4-29.8, and >29.8 kg/m(2), respectively). Noninflamed patients in BMI Q5 formed the reference group. During a median follow-up period of 36.7 months, 1929 deaths occurred (822 cardiovascular), with 655 patients censored for renal transplantation and 1183 for loss to follow-up. Greater mortality was observed in inflamed patients (P<0.001). In fully adjusted time-dependent analyses, the all-cause mortality risk in noninflamed patients was higher only in the lowest BMI quintile (hazard ratio [HR, 1.80; 95% confidence interval [95% CI], 1.26 to 2.56). No protective effect was associated with higher BMI quintiles in noninflamed patients. Conversely, higher BMI associated with lower all-cause mortality risk in inflamed patients (HR [95% CI] for Q1: 5.63 [4.25 to 7.46]; Q2: 3.88 [2.91 to 5.17]; Q3: 2.89 [2.16 to 3.89]; Q4: 2.14 [1.59 to 2.90]; and Q5: 1.77 [1.30 to 2.40]). Thus, whereas a protective effect of high BMI was observed in inflamed patients, this effect was mitigated in noninflamed patients.
authors.affiliation: Department of Renal Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; peter.stenvinkel@ki.se.
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
authors.affiliation: Center for Observational Research, Amgen Ltd., Uxbridge, United Kingdom;
authors.forename: Iain A
authors.initials: IA
authors.lastname: Gillespie
authors.affiliation: Global Biostatistical Science, Amgen Ltd., Cambridge, United Kingdom;
authors.forename: Jamie
authors.initials: J
authors.lastname: Tunks
authors.affiliation: Center for Observational Research, Amgen Ltd., Uxbridge, United Kingdom;
authors.forename: Janet
authors.initials: J
authors.lastname: Addison
authors.affiliation: Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria;
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.affiliation: French National Institute of Health and Medical Research (INSERM) Unit 1018, Hôpital Paul Brousse and Université Paris-Sud, Villejuif, France;
authors.forename: Tilman B
authors.initials: TB
authors.lastname: Drueke
authors.affiliation: Europe, Middle East, Africa and Latin America Medical Board, Fresenius Medical Care, Bad Homburg, Germany;
authors.forename: Daniele
authors.initials: D
authors.lastname: Marcelli
authors.affiliation: Department of Medicine I, Rudolfstiftung Hospital, Vienna, Austria;
authors.forename: Guntram
authors.initials: G
authors.lastname: Schernthaner
authors.affiliation: Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Germany;
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Eckardt
authors.affiliation: Department of Nephrology, RWTH University of Aachen, Aachen, Germany;
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.affiliation: International Development Nephrology, Amgen Europe GmbH, Zug, Switzerland; and.
authors.forename: Marc
authors.initials: M
authors.lastname: Froissart
authors.affiliation: Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
mesh_terms: D015992:Body Mass Index; D002423:Cause of Death; D015331:Cohort Studies; D006801:Humans; D007249:Inflammation / Q000150:complications; D007676:Kidney Failure, Chronic / Q000150:complications / Q000401:mortality* / Q000628:therapy*; D009765:Obesity / Q000150:complications; D006435:Renal Dialysis / Q000401:mortality*; D012306:Risk
keywords: chronic dialysis; chronic inflammation; obesity