Interaction between plasma matrix metalloproteinases and arsenic, cadmium, lead, and selenium on chronic kidney disease

Renal fibrosis, characterized by excessive extracellular matrix (ECM) deposition in the interstitium, is a hallmark of chronic kidney disease (CKD). Matrix metalloproteinases (MMPs), including MMP2 and MMP9, are zinc-dependent endopeptidases involved in ECM degradation and have been implicated in renal fibrosis. Exposure to metals and metalloids (collectively referred to as "metals") has been associated with CKD and may influence the expression of MMP2 and MMP9. Additionally, genetic polymorphisms in MMP2 and MMP9 may affect MMP expression. This study aimed to investigate the associations of plasma MMP2 and MMP9 concentrations and polymorphisms in MMP2 and MMP9 with CKD, as well as their interactions with metal exposure. A total of 215 patients with clinically diagnosed CKD and 389 age- and sex-matched controls were recruited. Plasma concentrations of MMP2 and MMP9 were measured using enzyme-linked immunosorbent assays. Plasma selenium, blood cadmium and lead, and total urinary arsenic concentrations were quantified. Common polymorphisms in MMP2 and MMP9 were genotyped. Logistic regression models were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the associations between these factors and CKD, adjusting for potential confounders. Elevated plasma concentrations of MMP2 and MMP9 were significantly associated with CKD, with ORs (95 % CIs) of 12.45 (6.04-25.66) and 3.77 (2.14-6.66), respectively. No associations were observed between the MMP2 or MMP9 genotypes and CKD. Significant additive interactions were identified between high plasma MMP2 levels and elevated total urinary arsenic, blood cadmium, blood lead, or plasma MMP9, as well as low plasma selenium levels, further increasing the association with CKD. Additionally, a significant multiplicative interaction was observed between high plasma MMP2 and elevated blood lead levels on CKD. To the best of our knowledge, this study is the first to identify the interactions between plasma MMP2 concentrations and metals on increasing the association of CKD.