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      Body Mass Index and Mortality in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis

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          Abstract

          Background: A higher body mass index (BMI) seems to be linked to survival advantage in maintenance hemodialysis patients. However, it is uncertain if this ‘obesity survival paradox' is also observed in kidney transplant recipients. Hence, we systematically reviewed the literature on the impact of pre-transplantation BMI on all-cause mortality in this population. Methods: We searched MEDLINE, EMBASE, Web of Science, CINAHL, and Cochrane CENTRAL for relevant studies up to July 2013. Two investigators independently selected the studies using predefined criteria, abstracted the data from the included studies, and independently assessed each study's quality using the Newcastle-Ottawa Quality Assessment Scale. In addition to the qualitative synthesis, we quantitatively pooled the results of the studies with clinical, methodological, and statistical homogeneity. Results: We screened 7,123 records, from which we included 11 studies (with a total of 305,392 participants) in this systematic review and 4 studies in the meta-analyses. In the only study that included children, obesity was linked to higher mortality in children of 6-12 years old. For adults, our meta-analyses indicated that compared to normal BMI, underweight [Hazard Ratio (HR): 1.09; 95% Confidence Interval (CI): 1.02-1.20], overweight (HR: 1.07; 95% CI: 1.04-1.12), and obese (HR: 1.20; 95% CI: 1.14-1.23) levels of BMI were associated with higher mortality. Conclusion: The presence of the obesity survival paradox is unlikely in kidney transplant recipients since both extremes of pre-transplantation BMI are linked to higher mortality in this population.

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          Most cited references 17

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          Obesity paradox in end-stage kidney disease patients.

          In the general population, obesity is associated with increased cardiovascular risk and decreased survival. In patients with end-stage renal disease (ESRD), however, an "obesity paradox" or "reverse epidemiology" (to include lipid and hypertension paradoxes) has been consistently reported, i.e. a higher body mass index (BMI) is paradoxically associated with better survival. This survival advantage of large body size is relatively consistent for hemodialysis patients across racial and regional differences, although published results are mixed for peritoneal dialysis patients. Recent data indicate that both higher skeletal muscle mass and increased total body fat are protective, although there are mixed data on visceral (intra-abdominal) fat. The obesity paradox in ESRD is unlikely to be due to residual confounding alone and has biologic plausibility. Possible causes of the obesity paradox include protein-energy wasting and inflammation, time discrepancy among competitive risk factors (undernutrition versus overnutrition), hemodynamic stability, alteration of circulatory cytokines, sequestration of uremic toxin in adipose tissue, and endotoxin-lipoprotein interaction. The obesity paradox may have significant clinical implications in the management of ESRD patients especially if obese dialysis patients are forced to lose weight upon transplant wait-listing. Well-designed studies exploring the causes and consequences of the reverse epidemiology of cardiovascular risk factors, including the obesity paradox, among ESRD patients could provide more information on mechanisms. These could include controlled trials of nutritional and pharmacologic interventions to examine whether gain in lean body mass or even body fat can improve survival and quality of life in these patients. © 2014.
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            Associations of pretransplant weight and muscle mass with mortality in renal transplant recipients.

            The association between pretransplant body composition and posttransplant outcomes in renal transplant recipients is unclear. It was hypothesized that in hemodialysis patients higher muscle mass (represented by higher pretransplant serum creatinine level) and larger body size (represented by higher pretransplant body mass index [BMI]) are associated with better posttransplant outcomes. Linking 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, 10,090 hemodialysis patients were identified who underwent kidney transplantation from July 2001 to June 2007. Cox regression hazard ratios and 95% confidence intervals of death and/or graft failure were estimated. Patients were 49 ± 13 years old and included 49% women, 45% diabetics, and 27% African Americans. In Cox models adjusted for case-mix, nutrition-inflammation complex, and transplant-related covariates, the 3-month-averaged postdialysis weight-based pretransplant BMI of 20 to <22 and < 20 kg/m(2), compared with 22 to <25 kg/m(2), showed a nonsignificant trend toward higher combined posttransplant mortality or graft failure, and even weaker associations existed for BMI ≥ 25 kg/m(2). Compared with pretransplant 3-month- averaged serum creatinine of 8 to <10 mg/dl, there was 2.2-fold higher risk of combined death or graft failure with serum creatinine <4 mg/dl, whereas creatinine ≥14 mg/dl exhibited 22% better graft and patient survival. Pretransplant obesity does not appear to be associated with poor posttransplant outcomes. Larger pretransplant muscle mass, reflected by higher pretransplant serum creatinine level, is associated with greater posttransplant graft and patient survival.
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              Effect of obesity on the outcome of kidney transplantation: a 20-year follow-up.

              Cardiovascular disease is both a major threat to the life expectancy of kidney transplant recipients and an important determinant of late allograft loss. Obesity is an important risk factor for cardiovascular disease. We investigated the relation between both pretransplant and 1-year posttransplant body mass index (BMI) with patient and renal graft survival in a cohort of 1810 adult patients. Sixty-one percent of all patients were men; median age (interquartile range [IQR]) was 46 years (35-56 years); median (IQR) pretransplant BMI was 23.0 kg/m (20.8-25.6 kg/m); 1 year after transplantation, the median (IQR) BMI had increased 1.6 kg/m (0.3-3.2 kg/m) and median (IQR) follow-up time was 8.3 years (5.3-12.0 years). We categorized BMI as follows: less than or equal to 20, more than 20 to less than or equal to 25 (normal), more than 25 to less than or equal to 30, and more than 30 (obesity) kg/m. Using a Cox proportional hazards model, after adjustment for cardiovascular risk factors, the relative risks (95% confidence intervals) of death and death-censored graft failure during all follow-up for pretransplant obesity compared with normal BMI were 1.22 (0.86-1.74) and 1.34 (1.02-1.77), respectively; for obesity 1 year after transplantation compared with normal BMI, it was 1.39 (1.05-1.86) and 1.39 (1.10-1.74), respectively; and for change in BMI (per 5 kg/m increment) during the first year after transplantation, it was 1.23 (1.01-1.50) and 1.18 (1.01-1.38), respectively. One year posttransplant BMI and BMI increment are more strongly related to death and graft failure than pretransplant BMI among kidney transplant recipients. Patients with BMI more than 30 kg/m compared with a normal BMI have approximately 20% to 40% higher risk for death and graft failure. © 2011 by Lippincott Williams & Wilkins
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2014
                November 2014
                21 October 2014
                : 40
                : 4
                : 315-324
                Affiliations
                aHarold Simmons Center for Kidney Disease Research and Epidemiology; Division of Nephrology and Hypertension, University of California Irvine Medical Center, Orange, Calif., bDepartment of Population Health and Disease Prevention, Program in Public Health, University of California Irvine, Irvine, Calif., cVeterans Affairs Long Beach Healthcare System, Long Beach, Calif., dMemphis Veterans Affairs Medical Center, and eDivision of Nephrology, University of Tennessee Health Science Center, Memphis, Tenn., fDepartment of Epidemiology, UCLA School of Public Health, Los Angeles, Calif., USA
                Author notes
                *Kamyar Kalantar-Zadeh, MD, MPH, PhD, Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, School of Medicine, 101 The City Drive South, City Tower, Orange, CA 92868-3217 (USA), E-Mail kkz@uci.edu
                Article
                367812 PMC4319181 Am J Nephrol 2014;40:315-324
                10.1159/000367812
                PMC4319181
                25341624
                © 2014 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 5, Tables: 1, Pages: 10
                Categories
                Original Report: Transplantation

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