The Obesity Paradox in Kidney Disease: How to Reconcile it with Obesity Management

• Published in: Kidney international reports 2017-03, Vol.2 (2), p.271-281
• Main Authors: Kalantar-Zadeh, Kamyar, Rhee, Connie M, Chou, Jason, Ahmadi, S Foad, Park, Jongha, Chen, Joline Lt, Amin, Alpesh N
• Format: Article
• Language: English
• Subjects: biologic plausibility; body mass index; fat mass; muscle mass; obesity paradox; protein−energy wasting; reverse epidemiology; World Kidney Day Mini Symposium on Kidney Disease and Obesity
• ISSN: 2468-0249; 2468-0249
• DOI: 10.1016/j.ekir.2017.01.009

Obesity, a risk factor for 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 the elderly. 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, i.e., 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 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 discover important pathophysiologic mechanisms leading to improved outcomes in patients with CKD.