NDT Advance Access originally published online on October 11, 2006
Nephrology Dialysis Transplantation 2007 22(2):560-567; doi:10.1093/ndt/gfl566
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The potential of matrix metalloproteinase-2 as a marker of peritoneal injury, increased solute transport, or progression to encapsulating peritoneal sclerosis during peritoneal dialysis—a multicentre study in Japan
Division of Nephrology, Department of Medicine, Jichi Medical School, 3311-1 Yakushiji, Shimotsuke-city, Tochigi 329-0498, Japan
Correspondence and offprint requests to: Ichiro Hirahara, Division of Nephrology, Department of Medicine, Jichi Medical School, 3311-1 Yakushiji, Shimotsuke-city, Tochigi, 329-0498, Japan. Email: hirahara{at}rpf.jp
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Abstract |
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Background. Long-term peritoneal dialysis (PD) leads to peritoneal injury. At worst, peritoneal injury leads to encapsulating peritoneal sclerosis (EPS), which is a serious complication of PD. The mortality rate of EPS is extremely high. To perform PD safely, monitoring of peritoneal injury that leads to EPS is a necessity.
Methods. A total of 444 PD patients with end-stage renal disease at 60 centres in Japan were analysed (sex, 54% males; median age, 56 years; median PD duration, 55 months). Matrix metalloproteinase (MMP)-2 and MMP-9 in the peritoneal effluents were analysed with gelatin zymography or enzyme-linked immunosorbent assay. Cells expressing MMP-2 in the peritoneal tissue were investigated immunohistologically with anti-MMP-2 antibodies. Peritoneal solute transport was assessed with the peritoneal equilibration test (PET).
Results. The MMP-2 levels in peritoneal effluents obtained with the PET were significantly correlated with the D/P Cr ratio (R = 0.69, P < 0.001) and the D/D0 glucose ratio (R = –0.59, P < 0.001). The MMP-2 levels in patients with mild peritoneal injury, moderate peritoneal injury, severe peritoneal injury (EPS) and infectious peritonitis were significantly higher than those in control patients (P < 0.001, P < 0.001, P < 0.01 and P < 0.05, respectively). MMP-2 was produced by myofibroblast-like mesenchymal cells and macrophages in the peritoneum. The peritoneal effluents from patients with infectious peritonitis showed strong MMP-9 signals.
Conclusions. From these results, MMP-2 levels in peritoneal effluents reflect peritoneal solute transport and changes in MMP-2 levels are associated with peritoneal injury that leads to EPS. MMP-2 may be a useful marker of peritoneal injury, increased solute transport or progression to EPS.
Keywords: encapsulating peritoneal sclerosis (EPS); matrix metalloproteinases (MMP); peritoneal dialysis; peritoneal injury
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