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Prog Cardiovasc Dis. 2018 Jul - Aug;61(2):168-181. doi: 10.1016/j.pcad.2018.07.001. Epub 2018 Jul 4.

Obesity Paradox in Advanced Kidney Disease: From Bedside to the Bench.

Author information

1
Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, School of Medicine, Orange, CA; Department of Internal Medicine, Tehran University of Medical Sciences, Tehran, Iran.
2
Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, School of Medicine, Orange, CA; Nephrology Section, Tibor Rubin VA Medical Center, Long Beach, CA.
3
Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, School of Medicine, Orange, CA; Nephrology Section, Tibor Rubin VA Medical Center, Long Beach, CA; Dept. of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA.
4
Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, School of Medicine, Orange, CA.
5
Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, School of Medicine, Orange, CA; Nephrology Section, Tibor Rubin VA Medical Center, Long Beach, CA; Dept. of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA. Electronic address: kkz@uci.edu.
6
Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California Irvine, School of Medicine, Orange, CA; Nephrology Section, Tibor Rubin VA Medical Center, Long Beach, CA. Electronic address: hmoradi@uci.edu.

Abstract

While obesity is associated with a variety of complications including diabetes, hypertension, cardiovascular disease and premature death, observational studies have also found that obesity and increasing body mass index (BMI) can be linked with improved survival in certain patient populations, including those with conditions marked by protein-energy wasting and dysmetabolism that ultimately lead to cachexia. The latter observations have been reported in various clinical settings including end-stage renal disease (ESRD) and have been described as the "obesity paradox" or "reverse epidemiology", engendering controversy. While some have attributed the obesity paradox to residual confounding in an effort to "debunk" these observations, recent experimental discoveries provide biologically plausible mechanisms in which higher BMI can be linked to longevity in certain groups of patients. In addition, sophisticated epidemiologic methods that extensively adjusted for confounding have found that the obesity paradox remains robust in ESRD. Furthermore, novel hypotheses suggest that weight loss and cachexia can be linked to adverse outcomes including cardiomyopathy, arrhythmias, sudden death and poor outcomes. Therefore, the survival benefit observed in obese ESRD patients can at least partly be derived from mechanisms that protect against inefficient energy utilization, cachexia and protein-energy wasting. Given that in ESRD patients, treatment of traditional risk factors has failed to alter outcomes, detailed translational studies of the obesity paradox may help identify innovative pathways that can be targeted to improve survival. We have reviewed recent clinical evidence detailing the association of BMI with outcomes in patients with chronic kidney disease, including ESRD, and discuss potential mechanisms underlying the obesity paradox with potential for clinical applicability.

KEYWORDS:

Body mass index; Cachexia; Chronic kidney disease; End stage renal disease; Mortality; Obesity; Obesity paradox

PMID:
29981348
PMCID:
PMC6131022
DOI:
10.1016/j.pcad.2018.07.001
[Indexed for MEDLINE]
Free PMC Article

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