Sex-Based Differences in the Association between Serum Copper and Kidney Function: Evidence from NHANES 2011-2016

Epidemiological evidence on the relationship between copper (Cu) and kidney function is rare, and few studies examine the sex differences in this association. We aimed to explore the overall and sex-based relationship between exposure to Cu and biomarkers of kidney function among 4331 participants of the 2011-2016 National Health and Nutrition Examination Survey. Multiple linear regression models were fitted to examine the overall and sex-specific associations between serum Cu and the kidney function indicator-estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR). Restricted cubic spline models (RCS) stratified by sex were performed to explore the sex-based dose-response associations. Serum Cu in the highest quartile was associated with higher levels of UACR (β = 0.203, 95% CI: 0.100 to 0.306) among overall participants. In males, there was an association of the highest Cu quartile with decreased eGFR (β = -0.023, 95% CI: -0.042 to -0.003) and increased UACR (β = 0.349, 95% CI: 0.171 to 0.527); serum Cu levels also demonstrated a negative nonlinear dose-response association with eGFR and a positive linear dose-response association with UACR in males, whereas females showed a marginally significant nonlinear positive association of eGFR with serum Cu levels. In conclusion, there were sex-specific and dose-response relationships between serum Cu and kidney function indicators. Further prospective and mechanistic studies are warranted.