Abstract

This study investigates the relationship between kidney function and exposure to low-level cadmium (Cd) and lead (Pb) in individuals with and without diabetes. Specifically, it tests the hypothesis that the nephrotoxicity of Cd and Pb reduces the tubular degradation of filtered proteins, namely β<inf>2</inf>-microglobulin (β<inf>2</inf>M). Data were obtained from a Thai cohort of 137 people, of which 65 were diagnosed with diabetes. Blood Cd, blood Pb, and urinary excretion of Cd (E<inf>Cd</inf>) were used as exposure indicators, while urinary N-acetylglucosaminidase (E<inf>NAG</inf>) and fractional tubular degradation of β<inf>2</inf>M (FrTD<inf>β2M</inf>) reflected kidney tubular cell injury and the function of tubular cells, respectively. Spearman’s rank correlation revealed that FrTD<inf>β2M</inf> varied directly with the estimated glomerular filtration rate (eGFR; r = 0.434), and inversely with fasting plasma glucose (r = −0.215), E<inf>Cd</inf> (r = −0.527), E<inf>NAG</inf> (r = −0.536), and Cd/Pb exposure (r = −0.249). In a multiple regression model analysis adjusting for potential confounders, the association between FrTD<inf>β2M</inf> and eGFR in those with diabetes was particularly strong (β = 0.476) compared to controls (β = 0.360), whereas an inverse association of FrTD<inf>β2M</inf> and E<inf>Cd</inf> (β = −0.295) was found only in those with diabetes, along with a positive association of E<inf>NAG</inf> with E<inf>Cd</inf> (R² = 0.071). A mediation analysis has revealed that tubular injury (E<inf>NAG</inf>) mediated 26% of the FrTD<inf>β2M</inf> decrease associated with Cd/Pb exposure. These findings suggested that tubular protein degradation pathways may be compromised under combined metabolic and environmental stressors, Cd, and Pb.