The Obesity Paradox in Kidney Disease: How to Reconcile It With Obesity Management

Abstract

Obesity, a risk factor for de novo chronic kidney disease (CKD), confers survival advantages in advanced CKD. This so-called obesity paradox is the archetype of the reverse epidemiology of cardiovascular risks, in addition to the lipid, blood pressure, adiponectin, homocysteine, and uric acid paradoxes. These paradoxical phenomena are in sharp contradistinction to the known epidemiology of cardiovascular risks in the general population. In addition to advanced CKD, the obesity paradox has also been observed in heart failure, chronic obstructive lung disease, liver cirrhosis, and metastatic cancer, as well as in elderly individuals. These are populations in whom protein−energy wasting and inflammation are strong predictors of early death. Both larger muscle mass and higher body fat provide longevity in these patients, whereas thinner body habitus and weight loss are associated with higher mortality. Muscle mass appears to be superior to body fat in conferring an even greater survival. The obesity paradox may be the result of a time discrepancy between competing risk factors, that is, overnutrition as the long-term killer versus undernutrition as the short-term killer. Hemodynamic stability of obesity, lipoprotein defense against circulating endotoxins, protective cytokine profiles, toxin sequestration of fat mass, and antioxidation of muscle may play important roles. Despite claims that the obesity paradox is a statistical fallacy and a result of residual confounding, the consistency of data and other causality clues suggest a high biologic plausibility. Examining the causes and consequences of the obesity paradox may help uncover important pathophysiologic mechanisms leading to improved outcomes in patients with CKD.

Preventive Nephrology: The Role of Obesity in Different Stages of Chronic Kidney Disease

“…Dual energy X-ray absorptiometry is routinely used for the assessment of fat mass in dialysis patients. Findings from different studies suggest that survival advantages from gaining fat mass is lower than from gaining lean body mass [22]. Using waist circumference as surrogate of intra-abdominal or visceral fat shows that each 10-cm increase in waist circumference was associated with higher all-cause and cardiovascular death [23].…”

“…Analysis of death rates in advanced CKD stages suggest that BMI > 40 was not associated with higher risks of death after excluding diabetes and hypertension from the risk model [22]. While larger body size by fluid retention is associated with poorer outcomes gaining body weight with increased fat and muscle mass (fat-free lean body mass) is favorable [2,22]. Anthropometry such as mid-arm muscle circumference can be used to estimate lean body mass.…”

Morbidity, mortality, and obesity paradox

“…The escalating prevalence of obesity and its link to substantial increase in metabolic and cardiovascular disease is a known fact (1). Current studies and meta-analyses, though, demonstrate with consistent effects, the presence of an "obesity paradox" among patients with several diseases such as coronary artery disease, chronic kidney disease, heart failure, atrial fibrillation, diabetes and patients undergoing cardiac surgery (2)(3)(4)(5)(6)(7)(8)(9)(10). This obesity paradox shows that lower (rather than higher) BMI is a risk factor for increased mortality (2)(3)(4)(5)(6)(7)(8)(9)(10).…”

“…Furthermore, obesity confers survival advantages in advanced chronic kidney disease (9). A retrospective study by Tsang et al investigated the potential association between BMI and overall survival in patients with distant metastases (10).…”

“…These mechanisms are hemodynamic stability of obesity, lipoprotein defense against circulating endotoxins, protective cytokine profiles, toxin sequestration of fat mass, and antioxidation of muscle may (9).…”