Chronic Kidney Disease and the Adiposity Paradox: Valid or Confounded?

Abstract

Objective: Obesity, defined by body mass index (BMI), is associated with lower mortality risk in patients with chronic kidney disease (CKD). BMI and % body fat (%BF) are confounded by muscle mass, while DXA derived fat mass index (FMI) overcomes this limitation. We compared the associations between obesity and mortality in persons with CKD using multiple estimates of adiposity, and determined whether muscle mass, inflammation and weight loss modify these associations.

Methods: Obesity was defined using BMI and DXA-derived FMI and %BF cut-offs in 2,852 NHANES participants with CKD from 1999-2006 and linked to the National Death Index with follow up through 2011. Cox proportional hazards models assessed associations between mortality and measures of obesity.

Results: Obesity based on FMI and continuous variables, FMI, BMI and %BF were associated with lower mortality. The protective association of obesity was less pronounced among participants with higher muscle mass and was no longer significant after adjustment for prior weight loss. Inflammation did not modify these associations.

Conclusions: We observed lower mortality associated with higher fat mass, particularly among persons with lower muscle mass. The prevalence of >10% weight loss was half as common among obese compared to non-obese participants and confounded these associations.

Figure 1A.

Hazard ratios and 95% confidence intervals for mortality in obese vs. non-obese persons with chronic kidney disease before and after adjustment for % weight loss. Chronic kidney disease was defined as eGFR <60 ml/min/1.73m² or urine albumin: creatinine ratio ≥ 25 mg/g for women and ≥ 17 mg/g for men. Model 3: Adjusted for age, sex, race, physical activity level, smoking status, diabetes, cancer, cardiovascular disease, liver disease, income and education. Model 4: Adjusted for percent weight loss category, age, sex, race, physical activity level, smoking status, diabetes, cancer, cardiovascular disease, and liver disease.

Figure 1B.

Hazard ratios and 95% confidence intervals for mortality by continuous measures of adiposity in persons with chronic kidney disease before and after adjustment for % weight loss. Chronic kidney disease was defined as eGFR <60 ml/min/1.73m² or urine albumin: creatinine ratio ≥ 25 mg/g for women and ≥ 17 mg/g for men. Model 3: Adjusted for age, sex, race, physical activity level, smoking status, diabetes, cancer, cardiovascular disease, liver disease, income and education. Model 4: Adjusted for percent weight loss category, age, sex, race, physical activity level, smoking status, diabetes, cancer, cardiovascular disease, and liver disease.