Higher Dialysate Matrix Metalloproteinase-2 Levels Are Associated with Peritoneal Membrane Dysfunction.

Abstract

UNLABELLED:

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BACKGROUND:

Peritoneal dialysis (PD) patients develop progressive and cumulative peritoneal injury with longer time spent on PD. The present study aimed to a) describe the trend of peritoneal injury biomarkers, matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1), in incident PD patients, b) to explore the capacity of dialysate MMP-2 to predict peritoneal solute transport rate (PSTR) and peritonitis, and c) to evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solution on these outcomes. ♦

METHODS:

The study included 178 participants from the balANZ trial who had at least 1 stored dialysate sample. Changes in PSTR and peritonitis were primary outcome measures, and the utility of MMP-2 in predicting these outcomes was analyzed using multilevel linear regression and multilevel Poisson regression, respectively. ♦

RESULTS:

Significant linear increases in dialysate MMP-2 and TIMP-1 concentrations were observed (p < 0.001), but neither was affected by the type of PD solutions received (MMP-2: p = 0.07; TIMP-1: p = 0.63). An increase in PSTR from baseline was associated with higher levels of MMP-2 (p = 0.02), and the use of standard solutions over longer PD duration (p = 0.001). The risk of peritonitis was independently predicted by higher dialysate MMP-2 levels (incidence rate ratio [IRR] per ng/mL 1.01, 95% confidence interval [CI] 1.005 - 1.02, p = 0.002) and use of standard solutions (Biocompatible solution: IRR 0.45, 95% CI 0.24 - 0.85, p = 0.01). ♦

CONCLUSION:

Dialysate MMP-2 and TIMP-1 concentrations increased with longer PD duration. Higher MMP-2 levels were associated with faster PSTR and future peritonitis risk. Administration of biocompatible solutions exerted no significant effect on dialysate levels of MMP-2 or TIMP-1, but did counteract the increase in PSTR and the risk of peritonitis associated with the use of standard PD solutions. This is the first longitudinal study to examine the clinical utility of MMP-2 as a predictor of patient-level outcomes.

• Authors: Yeoungjee Cho, David W Johnson, David A Vesey, Carmel M Hawley, Elaine M Pascoe, Margaret Clarke, Nicholas Topley, balANZ Trial Investigators
• Journal: Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis (Perit Dial Int) 2016 Jan-Feb Vol. 36 Issue 1 Pg. 16-25 ISSN: 1718-4304 [Electronic] United States
• PMID: 25292407 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 International Society for Peritoneal Dialysis.

Chemical References

• Biomarkers
• Hemodialysis Solutions
• Tissue Inhibitor of Metalloproteinase-1
• Matrix Metalloproteinase 2

Topics

• Aged
• Biomarkers (analysis)
• Female
• Hemodialysis Solutions (chemistry)
• Humans
• Male
• Matrix Metalloproteinase 2 (analysis)
• Middle Aged
• Peritoneal Dialysis
• Peritoneum (physiopathology)
• Tissue Inhibitor of Metalloproteinase-1 (analysis)