Elsevier

Progress in Cardiovascular Diseases

Volume 56, Issue 4, January–February 2014, Pages 415-425
Progress in Cardiovascular Diseases

Obesity Paradox in End-Stage Kidney Disease Patients

https://doi.org/10.1016/j.pcad.2013.10.005Get rights and content

Abstract

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.

Section snippets

Body size and mortality in HD patients

HD patients appear to have a lower BMI than age- and sex-matched control subjects from the general population.7 In a matched analysis comparing the lipid profiles of 285 HD patients with those of 285 non-ESRD patients matched in a one-to-one fashion on age, sex, race, and diabetes, BMI was found to be significantly lower in the HD patients than in the control subjects (26.2 ± 6.0 compared with 31.5 ± 7.8 kg/m2, P < 0.001).8 A lower BMI was consistently found to be a strong predictor of increased

Body size and mortality in PD patients

Similar inverse associations between body size and mortality have been observed in some studies with PD patients, but a survival advantage associated with large body size seemed to be less likely in PD than HD patients31 (Table 2), although comparisons are limited by methodological differences across studies, including the use of different BMI categories. In the Canada-USA (CANUSA) Peritoneal Dialysis Study Group, 1% lower lean body mass estimated from creatinine kinetics was associated with a

Body composition and mortality in ESRD patients

BMI may not be an optimal surrogate of visceral obesity when compared to waist circumference, which better reflects intra-abdominal (truncal) fat. Indeed Postorino et al.40 showed that surrogate measures of abdominal obesity and segmental fat distribution (waist circumference and waist/hip ratio) were stronger predictors of all-cause and CVD death than BMI in 537 patients with ESRD. In this study, higher BMI was protective whereas higher waist circumference was a predictor of higher mortality.40

Possible explanations for the obesity paradox

The obesity paradox has been also observed in other populations such as the elderly46 and in patients with congestive heart failure.47., 48. The obesity paradox may appear counterintuitive, because obesity is an established risk factor for CVD and poor outcomes in the general population. Indeed, it is not only lack of an association between obesity and mortality, but the opposite direction of this relation. Hence, there must be prevailing conditions that are uniquely present in ESRD patients,

Remaining questions and future studies

The obesity paradox of CVD mortality in ESRD patients may have indeed serious clinical and public health implications. Is the survival advantage of obesity in ESRD patients a clinically valid characteristic, or is it a statistical fallacy that needs to be ‘controlled away’?88 Does obesity which promotes atherosclerosis and mortality in the general population, prevent cardiovascular death in ESRD patients and, if so, how? Should ESRD patients be advised to increase their nutrient intake to gain

Statement of Conflict of Interest

The author declares there are no conflicts of interest.

Acknowledgments

KKZ and CPK are supported by the National Institute of Diabetes, Digestive and Kidney Disease grants R01-DK078106 and R01-DK096920, and KKZ is supported additionally by grant K24-DK091419 and a philanthropist grant from Mr. Harold Simmons. MZM and KKZ are supported by the National Institute on Aging of the National Institutes of Health grant R21-AG047036. Disclaimer: The findings and conclusions in this report are those of the authors and not necessarily of the Centers for Disease Control and

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    Statement of Conflict of Interest: see page 422.

    1

    Correspondence: Kamyar Kalantar-Zadeh, MD PhDMPH, Harold Simmons Center, Division of Nephrology and Hypertension, University of California Irvine Medical Center, 101 The City Drive South, City Tower, Suite 400 - ZOT: 4088, Orange, CA 92868.

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