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Peritonitis increases MMP-9 activity in peritoneal effluent from CAPD patients

K Fukudome1, S Fujimoto, Y Sato

  • 1First Department of Internal Medicine, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.

Nephron
|February 15, 2001
PubMed

Insights

Peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients elevates matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). These changes may contribute to peritoneal extracellular matrix remodeling and ultrafiltration failure.

Area of Science:

  • Nephrology
  • Biochemistry
  • Pathology

Background:

  • Continuous ambulatory peritoneal dialysis (CAPD) patients can develop ultrafiltration failure.
  • Peritoneal fibrosis, characterized by mesothelial basement membrane thickening and submesothelial tissue accumulation, is linked to ultrafiltration failure.
  • The exact mechanisms by which peritonitis causes ultrafiltration failure remain unclear.

Purpose of the Study:

  • To investigate the role of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in peritoneal extracellular matrix (ECM) remodeling during peritonitis in CAPD patients.
  • To determine if MMP and TIMP activities in peritoneal effluent correlate with peritonitis severity.

Main Methods:

  • Analysis of peritoneal effluent from CAPD patients with peritonitis (n=13) and non-infected controls (n=7).
  • Gelatin and reverse zymography were used to assess MMP and TIMP activities.
  • Correlation analysis between enzyme activities, leukocyte counts, and IL-6 levels.

Main Results:

  • Latent and activated forms of MMP-2, MMP-9, TIMP-1, and TIMP-2 were detected in all patients.
  • Elevated levels of latent and activated MMP-9 and TIMP-1 were observed at the onset of peritonitis compared to recovery or control groups.
  • Activated MMP-9 levels correlated positively with leukocyte counts and IL-6 levels.

Conclusions:

  • Increased MMP-9 and TIMP-1 levels in peritoneal effluent are associated with peritoneal ECM remodeling during peritonitis.
  • These MMP/TIMP alterations may play a role in the pathogenesis of ultrafiltration failure in CAPD patients.

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