Higher dialysate matrix metalloproteinase-2 levels are associated with peritoneal membrane dysfunction

Cho, Yeoungjee, Johnson, David W., Vesey, David A., Hawley, Carmel M., Pascoe, Elaine M., Clarke, Margaret and Topley, Nicholas (2016) Higher dialysate matrix metalloproteinase-2 levels are associated with peritoneal membrane dysfunction. Peritoneal Dialysis International, 36 1: 16-25. doi:10.3747/pdi.2013.00274

Author Cho, Yeoungjee
Johnson, David W.
Vesey, David A.
Hawley, Carmel M.
Pascoe, Elaine M.
Clarke, Margaret
Topley, Nicholas
Title Higher dialysate matrix metalloproteinase-2 levels are associated with peritoneal membrane dysfunction
Journal name Peritoneal Dialysis International   Check publisher's open access policy
ISSN 1718-4304
Publication date 2016-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.3747/pdi.2013.00274
Open Access Status Not Open Access
Volume 36
Issue 1
Start page 16
End page 25
Total pages 10
Place of publication Milton, ON, Canada
Publisher Multimed
Collection year 2017
Language eng
Formatted abstract
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.
Keyword Biocompatible
Glucose degradation products
Matrix metalloproteinase-2
Peritoneal dialysis
Peritoneal solute transport rate
Tissue inhibitor of metalloproteinase-1
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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