Abstract: Objective To investigate the association between urinary levels of six metals (aluminum, titanium, copper, zinc, molybdenum, and cadmium) and renal function decline in patients with diabetes and/or hypertension in Guangzhou, China. Methods In 2023, participants with diabetes, hypertension, or both were enrolled and grouped accordingly to their medical conditions (diabetes group, hypertension group, diabetes with hypertension group). Urinary metal concentrations were measured, and renal function was assessed using estimated glomerular filtration rate (GFR) derived from serum creatinine (Cr). Logistic regression and Weighted Quantile Sum (WQS) regression models were employed to evaluate associations between urinary metal levels and renal function decline (binary outcome). Results A total of 1 414 patients with diabetes and/or hypertension were surveyed in Guangzhou, with an average age of (63.7 ± 9.6) years. Among them, 558 were male (39.5%) and 856 were female (60.53%). Renal function decline was observed in 91 participants (6.9%). Median urinary metal concentrations were: aluminum (31.47 μg/L), titanium (103.25 μg/L), copper (9.23 μg/L), zinc (306.12 μg/L), molybdenum (48.44 μg/L), and cadmium (1.50 μg/L). Univariate logistic regression revealed significant associations between renal function decline and copper (OR=1.98), zinc (OR=1.45), and molybdenum (OR=1.41). After stratification, only copper was significantly correlated with decreased renal function (P<0.05). The WQS regression indicated a positive combined effect of the six metals on renal function decline (OR=1.39), with copper contributing the highest weight (61.0%). The RCS model demonstrated a V-shape between titanium levels and eGFR, and a negative correlation between copper levels and eGFR (P_non-linear<0.05). Conclusions This study revealed a close relationship between urinary copper levels and declining renal function in patients with diabetes and hypertension. Moreover, copper ions appear to cause more severe kidney damage in patients with diabetes than in those with hypertension or diabetes combined with hypertension.

Key words: Diabetes, Hypertension, Aluminum, Titanium, Copper, Zinc, Molybdenum, Cadmium, Estimated glomerular filtration Rate (eGFR)