Metabolic phenotypes of excess body weight and risk of impaired kidney function

Introduction: Excess body weight and metabolic syndrome are major public health problems worldwide that frequently coexist, and are both risk factors for reduced kidney function (RKF). However, some people with excess body weight do not present metabolic abnormalities and are considered metabolically healthy (MHEW). Several studies reported that people with excess body weight had a higher risk for RKF, independently from the metabolic phenotype, than healthy people with normal weight. However, it is unknown if MHEW have a different risk of impaired kidney function from metabolically unhealthy people with excess body weight (MUEW). Methods: A cross-sectional study of 8263 participants (67.5% females, mean age: 47±13 years) with overweight (52.9%) and obesity (47.1%) recruited at the International Center for the Assessment of Nutritional Status (ICANS, University of Milan) was carried out. Anthropometric measurements (weight, height, and waist circumference (WC)), blood pressure, blood parameters (glucose, triglycerides, HDL-cholesterol, and creatinine) were taken. Lifestyle-related information (physical activity and smoking habits) were investigated. MHEW were defined as people with overweight or obesity but free of metabolic abnormalities defined according harmonized criteria for metabolic syndrome (with exclusion of WC). MUEW were defined as people with overweight or obesity and at least one metabolic syndrome criteria (with exclusion of WC). Glomerular filtration rate (eGFR) was calculated through the EPI-CKD predictive formula. Normal renal function was defined as eGFR 90-125 ml/min/1.73m². Higher values indicated hyperfiltration, values ranged 60-89 ml/min/1.73m² a mild RKF, while values <60 ml/min/1.73m² indicated a moderate/severe RKF. A multinomial logistic model adjusted for sex, age, BMI, smoking and physical activity was used to assess the impact of the metabolic phenotypes on the risk of hyperfiltration, mild RKF and moderate/severe RKF, which lead to odd ratio (OR) as measure of association. In the model, people with hyperfiltration, mild RKF and moderate/ severe RKF were compared with people with normal renal function. Results: Overall, the prevalence of MHEW was 27.1% and decreased with increasing obesity class. Overall, 4.0% presented hyperfiltration, 29.8% a mild RKF, and 2.1% had a moderate/severe RKF. eGFR was significantly higher in MHEW people than in MUEW (103.1±16.2 vs. 95.2±17.1 ml/ min/1.73m², p<0.001). In the multinomial logistic model adjusted for sex, age, BMI, smoking and physical activity, MHEW were more likely to be affected by hyperfiltration than MUEW (OR=1.41, 95%CI:1.06,1.87, p=0.019). On the other hand, compared to MHEW, MUEW were more likely to be affected by moderate/severe RKF (OR=2.34, 95%CI:1.12,4.89, p=0.023). No association was found between metabolic phenotypes of excess body weight and mild RKF. Conclusion: Metabolic phenotypes of excess body weight were associated with the risk of impaired kidney function. In particular, people with only excess body weight had a higher risk for hyperfiltration, while the presence of metabolic alterations was associated with a higher risk for moderate/severe RKF.