title: Examining the robustness of the obesity paradox in maintenance hemodialysis patients: a marginal structural model analysis.
abstract: The inverse association between body mass index (BMI) and mortality observed in patients treated with maintenance hemodialysis (MHD), also known as the obesity paradox, may be a result of residual confounding. Marginal structural model (MSM) analysis, a technique that accounts for time-varying confounders, may be more appropriate to investigate this association. We hypothesize that after applying MSM, the inverse association between BMI and mortality in MHD patients is attenuated.
  
  
  
  We examined the associations between BMI and all-cause mortality among 123 624 adult MHD patients treated during 2001-6. We examined baseline and time-varying BMI using Cox proportional hazards models and MSM while considering baseline and time-varying covariates, including demographics, comorbidities and markers of malnutrition and inflammation.
  
  
  
  The patients included 45% women and 32% African Americans with a mean age of 61(SD 15) years. In all models, BMI showed a linear incremental inverse association with mortality. Compared with the reference (BMI 25 to <27.5 kg/m(2)), a BMI of <18 kg/m(2) was associated with a 3.2-fold higher death risk [hazard ratio (HR) 3.17 (95% CI 3.05-3.29)], and mortality risks declined with increasing BMI with the greatest survival advantage of 31% lower risk [HR 0.69 (95% CI 0.64-0.75)] observed with a BMI of 40 to <45 kg/m(2).
  
  
  
  The linear inverse relationship between BMI and mortality is robust across models including MSM analyses that more completely account for time-varying confounders and biases.
authors.affiliation: Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, School of Medicine, Orange, CA, USA.
authors.forename: Megha
authors.initials: M
authors.lastname: Doshi
authors.affiliation: Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, School of Medicine, Orange, CA, USA.
authors.forename: Elani
authors.initials: E
authors.lastname: Streja
authors.affiliation: Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, School of Medicine, Orange, CA, USA.
authors.forename: Connie M
authors.initials: CM
authors.lastname: Rhee
authors.affiliation: Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, School of Medicine, Orange, CA, USA Division of Nephrology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
authors.forename: Jongha
authors.initials: J
authors.lastname: Park
authors.affiliation: Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, School of Medicine, Orange, CA, USA.
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Ravel
authors.affiliation: Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, School of Medicine, Orange, CA, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Soohoo
authors.affiliation: Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, School of Medicine, Orange, CA, USA Department of Medicine, Long Beach Veteran Affairs Health System, Long Beach, CA, USA.
authors.forename: Hamid
authors.initials: H
authors.lastname: Moradi
authors.affiliation: Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, School of Medicine, Orange, CA, USA.
authors.forename: Wei Ling
authors.initials: WL
authors.lastname: Lau
authors.affiliation: Harborview Medical Center and Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Rajnish
authors.initials: R
authors.lastname: Mehrotra
authors.affiliation: Harborview Medical Center and Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Sooraj
authors.initials: S
authors.lastname: Kuttykrishnan
authors.affiliation: Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN, USA Nephrology Section, Memphis Veterans Affairs Medical Center, Memphis, TN, USA.
authors.forename: Csaba P
authors.initials: CP
authors.lastname: Kovesdy
authors.affiliation: Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, School of Medicine, Orange, CA, USA Department of Medicine, Long Beach Veteran Affairs Health System, Long Beach, CA, USA Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA, USA.
authors.forename: Kamyar
authors.initials: K
authors.lastname: Kalantar-Zadeh
authors.affiliation: Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, School of Medicine, Orange, CA, USA Department of Medicine, Long Beach Veteran Affairs Health System, Long Beach, CA, USA.
authors.forename: Joline L T
authors.initials: JL
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000401:mortality; D016016:Proportional Hazards Models; D006435:Renal Dialysis; D015996:Survival Rate / Q000639:trends; D014481:United States / Q000453:epidemiology; D055815:Young Adult
keywords: cardiovascular; dialysis; epidemiology; nutrition; obesity