The body mass index paradox and an obesity, inflammation, and atherosclerosis syndrome in chronic kidney disease.
The association of high body mass index (BMI) with better survival in chronic kidney disease (CKD) is considered a "risk factor paradox" or "reverse epidemiology." Since malnutrition is a powerful predictor of death and cardiovascular disease is its leading cause, it has been suggested that malnutrition and atherosclerosis must be associated. Thus the current paradigm is that malnutrition is a risk factor for atherosclerosis and obesity is protective in CKD patients. We recently showed that high-BMI patients with inferred high body fat have an increased prevalence of atherosclerosis and subsequent cardiovascular and all-cause mortality. Prior cross-sectional studies also showed that high BMI in CKD is associated with higher C-reactive protein (CRP) levels and increased coronary calcification on electron beam computed tomography (CT) scan. These apparently conflicting data on better survival but increased inflammation and atherosclerosis in high-BMI CKD patients could be explained as follows. It is hypothesized that nutrition exerts a much stronger influence on survival than atherosclerosis in CKD. Malnutrition strongly augments the hazard of death from coexistent diseases, while better nutrition has the opposite effect. Thus the risk of death is highest in malnourished patients (low muscle and low fat mass) and lowest in well-nourished patients (high BMI, high muscle mass). Obesity (high BMI, high fat mass) is associated with inflammation and atherosclerosis. The risk of death from obesity and atherosclerosis is increased, but not so much as occurs with malnutrition. Therefore high body fat patients have intermediate survival. Thus it is postulated that an association of obesity, inflammation, and atherosclerosis (OIA syndrome) might exist in CKD.
Beddhu
Srinivasan
S
Renal Section, Salt Lake VA Healthcare System and Division of Nephrology and Hypertension, University of Utah School of Medicine, Salt Lake City, Utah, USA. Srinivasan.beddhu@hsc.utah.edu
D001161:Arteriosclerosis / Q000453:epidemiology*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D002908:Chronic Disease; D015897:Comorbidity; D006801:Humans; D007674:Kidney Diseases / Q000453:epidemiology* / Q000401:mortality; D044342:Malnutrition / Q000453:epidemiology*; D009765:Obesity / Q000453:epidemiology*; D018384:Oxidative Stress; D012307:Risk Factors
D002097:C-Reactive Protein