Metabolic Subtypes and Risk of Mortality in Normal Weight, Overweight, and Obese Individuals with CKD

Higher body mass index (BMI) is paradoxically associated with lower mortality in persons with CKD, but whether cardiometabolic abnormalities modulate this association is unclear.Participants with CKD from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study (n=4374) were analyzed. The harmonized criteria for metabolic syndrome were used to define metabolic health, and participants were categorized into one of six mutually exclusive categories defined by combined measures of metabolic health (metabolically healthy, <3 criteria for metabolic syndrome; metabolically unhealthy, ≥3 criteria) and weight status (normal weight, BMI 18.5-24.9 kg/m(2); overweight, BMI 25-29.9 kg/m(2); obese, BMI ≥30 kg/m(2)). Cox models were used to estimate the hazard ratio (HR) of death as a function of each category.A total of 683 deaths were observed over a mean 4.5 years of follow-up. In analyses adjusted for age, race, sex, and geographic region of residence, compared with metabolically healthy normal weight persons, the HRs of mortality in metabolically healthy overweight and obese persons were 0.68 (95% confidence interval [95% CI], 0.53 to 0.87) and 0.71 (95% CI, 0.51 to 0.98), respectively, whereas there were no statistically significant differences in survival among metabolically unhealthy overweight or obese individuals. After further adjustment for lifestyle, clinical and laboratory factors including markers of kidney function, the HR of mortality remained lower in metabolically healthy overweight individuals compared with metabolically healthy normal weight individuals (HR, 0.74; 95% CI, 0.57 to 0.96).Metabolic abnormalities may attenuate the magnitude and strength of survival benefits associated with higher BMI in individuals with CKD.