What does the dialysate level of matrix metalloproteinase 2 tell us?

Long-term peritoneal dialysis leads to encapsulating peritoneal sclerosis (EPS), which is a rare but often fatal complication. The pathogenesis of EPS is characterized by increased inflammation, neoangiogenesis, epithelial-mesenchymal transition (EMT), and fibrosis. Matrix metalloproteinase 2 (MMP-2), which degrades type IV collagen, plays an important role in pathogenesis. Clinical trials report that dialysate levels of MMP-2 can be used as an early marker of peritoneal sclerosis. We aimed to determine the association of MMP-2 with peritoneal function, histology, and effluent cytokine levels in an experimental EPS model in rats. We evaluated data for 71 rats from our various studies using an experimental EPS model. Functional assessment was performed using a 1-hour peritoneal equilibration test with peritoneal dialysis fluid containing 3.86% glucose. Specimens of parietal peritoneum were examined with light microscopy for histologic evaluation. Parietal peritoneum thickness and submesothelial area were measured. Fibrosis, number of vessels, neovascularization, and cellular infiltration were evaluated by one pathologist. The relationships between MMP-2 and other parameters were analyzed using Pearson correlation analysis. Dialysate levels of MMP-2 reflect both functional and histologic change in peritoneum. Levels of MMP-2 were negatively correlated with net ultrafiltration, effluent protein levels, and end (1-hour)-to-initial dialysate concentration ratio of glucose. Cytokines such as vascular endothelial growth factor transforming growth factor beta, monocyte chemotactic protein 1, and osteopontin-which are known to play important roles in neovascularization, inflammation, and EMT leading to fibrosis-were correlated with MMP-2. In peritoneal dialysis patients, MMP-2 levels may be an early marker of EPS and EMT