Copper/Zinc Ratio as a Predictor of Chronic Kidney Disease Incidence in Type 2 Diabetes: The Asahi Diabetes Complications Study

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Aim This study aims to evaluate the associations between the copper/zinc (Cu/Zn) ratio and inflammatory biomarkers and the incidence of chronic kidney disease (CKD) in individuals with type 2 diabetes and to validate our previous cross-sectional study using the baseline data of this study. Methods We conducted a prospective, observational study of 416 individuals with type 2 diabetes without CKD. We used multivariable Cox proportional hazard models to determine the HRs for CKD incidence. The Cu/Zn ratio and soluble tumor necrosis factor-α receptor 1 (sTNFαR1) concentrations (pg/mL) were analyzed as continuous variables and as categories classified according to each cutoff value for detecting CKD. The high-sensitivity C-reactive protein (hsCRP) concentrations between these categories were compared. Results CKD was identified in 165 participants. The Cu/Zn ratio and sTNFαR1 concentrations were identified as significant predictors, independent of each other, after full adjustment (P = 0.048 and P = 0.006, respectively). Compared to the Cu/Zn <1.281 and sTNFαR1 <1081 group, the HRs for the CKD incidence were significantly higher in the Cu/Zn <1.281 and sTNFαR1 ≥1081 group (HR 2.06, 95% CI 1.34-3.26) and even higher in the Cu/Zn ≥1.281 and sTNFαR1 ≥1081 group (3.29, 1.97-5.50) after full adjustment. The hsCRP concentrations were significantly highest in the Cu/Zn ≥1.281 and sTNFαR1 ≥1081 group compared with the other three groups (all P < 0.05) and were significantly higher in the Cu/Zn ≥1.281 and sTNFαR1 <1081 group and in the Cu/Zn <1.281 and sTNFαR1 ≥1081 group compared with those in the Cu/Zn <1.281 and sTNFαR1 <1081 group (both P < 0.05). Conclusions The Cu/Zn ratio and sTNFαR1 concentrations are independent predictors of the incidence of CKD in individuals with type 2 diabetes. Furthermore, under elevated sTNFαR1 concentrations, an increase in the Cu/Zn ratio may further aggravate inflammation and accelerate the incidence of CKD in individuals with type 2 diabetes. These new findings are supported by the results from our previous cross-sectional study.