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Higher Dialysate Matrix Metalloproteinase-2 Levels Are Associated with Peritoneal Membrane Dysfunction
Yeoungjee Cho1, David W Johnson2, David A Vesey1
1Department of Renal Medicine, Princess Alexandra Hospital, Brisbane, Australia School of medicine, University of Queensland, Brisbane, Australia Translational Research Institute, Brisbane, Australia.
Unlabelled:
♦
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.
Insights
Peritoneal dialysis patients show increasing peritoneal injury biomarkers, MMP-2 and TIMP-1, over time. Higher MMP-2 levels predict faster solute transport and increased peritonitis risk, while biocompatible solutions mitigate these risks.
Area of Science:
- Nephrology
- Biomarker Research
- Peritoneal Dialysis
Background:
- Peritoneal dialysis (PD) is associated with progressive peritoneal injury over time.
- Matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) are key biomarkers of this injury.
- Understanding these biomarkers' trends and predictive capacity is crucial for PD patient management.
Purpose of the Study:
- To track trends of MMP-2 and TIMP-1 in incident PD patients.
- To assess MMP-2's ability to predict peritoneal solute transport rate (PSTR) and peritonitis.
- To evaluate the impact of neutral pH, low glucose degradation product (GDP) PD solutions on these outcomes.
Main Methods:
- Analysis of dialysate samples from 178 participants in the balANZ trial.
- Utilized multilevel linear regression for PSTR and multilevel Poisson regression for peritonitis prediction.
- Investigated the association between MMP-2, TIMP-1, PSTR, peritonitis, and PD solution type.
Main Results:
- Dialysate MMP-2 and TIMP-1 concentrations significantly increased with longer PD duration.
- Higher MMP-2 levels correlated with increased PSTR and a higher risk of peritonitis.
- Biocompatible PD solutions did not alter MMP-2/TIMP-1 levels but reduced PSTR and peritonitis risk compared to standard solutions.
Conclusions:
- MMP-2 and TIMP-1 are reliable indicators of peritoneal injury progression in PD patients.
- Elevated MMP-2 levels serve as a predictive marker for adverse patient outcomes, including faster PSTR and peritonitis.
- Biocompatible solutions offer a protective effect against PD-related complications, independent of MMP-2/TIMP-1 levels.
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