Interrelationship of environmental melamine exposure, biomarkers of oxidative stress and early kidney injury

ABSTRACT Melamine contamination has remained pervasive in the environment even after the 2008 toxic milk scandal. Exposure to chronic low dosages of melamine is known to induce renal tubular damage, increasing the risk of stone formation and early kidney injury. This damage may come about via increased oxidative stress, but no studies of this possibility have been performed in humans. We conducted two human studies in 80 workers from melamine tableware factories (melamine workers) and 309 adult patients with calcium urolithiasis (stone patients) to evaluate the relationships between urinary melamine levels and two urinary biomarkers of oxidative stress, 8-oxo-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA). Both human studies showed urinary melamine levels to be significantly and positively correlated with urinary 8-OHdG and MDA, indicating melamine exposure can increase oxidative stress. Additionally, we used structure equation modeling to evaluate relative contribution of type of melamine-induced oxidative stress on renal tubular injury and found that MDA mediated 36%-53% of the total effect of melamine on a biomarker of renal tubular injury, N-Acetyl-β-D Glucosaminidase (NAG). In conclusion, our findings suggest exposure to low-dose melamine can increase oxidative stress and increase the risk of early damage to kidneys in humans.