Obesity Without Metabolic Abnormality and Incident CKD: A Population-Based British Cohort Study

Rationale & Objective Metabolically healthy obesity (obesity without any metabolic abnormality) is not considered to be associated with increased risk of morbidity and mortality. We examined and quantified the association between metabolically healthy overweight/obesity and the risk of incident chronic kidney disease (CKD) in a British primary care population. Study Design Retrospective population-based cohort study. Setting & Participants 4,447,955 of the 5,182,908 adults in The Health Improvement Network (THIN) database (United Kingdom, 1995-2015) with a recorded body mass index (BMI) at the time of registration date who were free of CKD and cardiovascular disease. Exposure 11 body size phenotypes were created, defined by BMI categories (underweight, normal weight, overweight, and obesity) and 3 metabolic abnormalities (diabetes, hypertension, and dyslipidemia). Outcome Incident CKD defined as a recorded code for kidney replacement therapy, a recorded diagnosis of CKD, or by an estimated glomerular filtration rate of  3 mg/mmol for ≥90 days. Results Of the 4.5 million individuals, 1,040,921 (23.4%) and 588,909 (13.2%) had metabolically healthy overweight and metabolically healthy obesity, respectively. During a mean follow-up interval of 5.4 ± 4.3 (SD) years, compared with individuals with a metabolically healthy normal weight (n = 1,656,231), there was a higher risk of incident CKD among those who had metabolically healthy overweight (adjusted HR, 1.30 [95% CI, 1.28-1.33]) and metabolically healthy obesity (adjusted HR, 1.66 [95% CI, 1.62-1.70]). The association was stronger in those younger than 65 years of age. In all BMI categories, there was greater risk of incident CKD with a greater number of metabolic abnormalities in a graded manner. Limitations Potential misclassification of metabolic status due to delayed diagnosis and residual confounding due to unmeasured factors. Conclusions Overweight and obesity without metabolic abnormality are associated with a higher risk of incident CKD compared with those with normal body weight and no metabolic abnormality.