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Multicenter Study
. 2016 Aug;31(8):1310-9.
doi: 10.1093/ndt/gfv379. Epub 2015 Nov 19.

Examining the robustness of the obesity paradox in maintenance hemodialysis patients: a marginal structural model analysis

Megha Doshi  1 , Elani Streja  1 , Connie M Rhee  1 , Jongha Park  2 , Vanessa A Ravel  1 , Melissa Soohoo  1 , Hamid Moradi  3 , Wei Ling Lau  1 , Rajnish Mehrotra  4 , Sooraj Kuttykrishnan  4 , Csaba P Kovesdy  5 , Kamyar Kalantar-Zadeh  6 , Joline L T Chen  3
Affiliations
Multicenter Study

Examining the robustness of the obesity paradox in maintenance hemodialysis patients: a marginal structural model analysis

Megha Doshi et al. Nephrol Dial Transplant. 2016 Aug.

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: cardiovascular; dialysis; epidemiology; nutrition; obesity.

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Figures

FIGURE 1:
FIGURE 1:
Cohort construction.
FIGURE 2:
FIGURE 2:
Hazard ratios (95% CI) for the associations between BMI categories (reference: 25 to <27.5 kg/m2) and all-cause mortality obtained from baseline, time-varying and MSM models. Models adjusted for case-mix covariates and markers of malnutrition and inflammation (see text for covariate list).
FIGURE 3:
FIGURE 3:
Hazard ratios (95% CI) for the associations between BMI categories (reference: 25 to <27.5 kg/m2) and cardiovascular mortality obtained from baseline, time-varying and MSM models. Models adjusted for case-mix covariates and markers of malnutrition and inflammation (see text for covariate list).
FIGURE 4:
FIGURE 4:
Subgroup analyses of the association between BMI categories (<18, 18 to <20, 20 to <21.5, 21.5 to <23, 23 to <25, 25 to <27.5 reference, 27.5 to <30, 30 to <35, 35 to <40, 40 to <45 and ≥45 kg/m2) and all-cause mortality using a MSM. Models adjusted for case-mix covariates and markers of malnutrition and inflammation (see text for covariate list).
FIGURE 5:
FIGURE 5:
Subgroup analyses of the association between BMI categories (<18, 18 to <20, 20 to <21.5, 21.5 to <23, 23 to <25, 25 to <27.5 reference, 27.5 to <30, 30 to <35, 35 to <40, 40 to <45 and ≥45 kg/m2) and cardiovascular mortality using a MSM. Models adjusted for case-mix covariates and markers of malnutrition and inflammation (see text for covariate list).
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