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Peritoneal effluent MMP-2 and PAI-1 in encapsulating peritoneal sclerosis
Deirisa Lopes Barreto1, Dirk G Struijk2, Raymond T Krediet1
1Division of Nephrology, Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam.
Background:
Recently, the use of effluent matrix metalloproteinase 2 (MMP-2) and plasminogen activator inhibitor 1 (PAI-1) as potential biomarkers of peritoneal fibrosis has been demonstrated during longitudinal follow-up of incident peritoneal dialysis (PD) patients. This study focuses on effluent MMP-2 and PAI-1 as early diagnostic markers in the preceding years of patients who develop encapsulating peritoneal sclerosis (EPS).
Study Design:
Diagnostic test study.
Settings & Participants:
PD patients who developed EPS were compared with controls using a 1:3 case-control design with a minimum PD duration of 57 months.
Index Tests:
Dialysate appearance rates of MMP-2 and PAI-1.
Reference Test:
EPS cases identified by 2 experienced nephrologists and a radiologist based on predefined criteria.
Results:
11 patients developed EPS within our center. The time course of MMP-2 appearance rates, studied by means of a linear repeated-measures model 4 years prior to the diagnosis of EPS, showed no difference between long-term controls and patients with EPS. In contrast, higher PAI-1 appearance rates were found in patients with EPS compared with controls (P=0.01). At a lag time of 1 year prior to EPS diagnosis, time-specific receiver operating characteristic curve analyses indicated a discriminative ability for PAI-1 appearance rate of 0.77 (95% CI, 0.63-0.91). A discriminative capacity was absent for those of MMP-2.
Limitations:
Low event rate of EPS prevented independent validation in this single-center study.
Conclusions:
Elevated levels of PAI-1 appearance rates are present in patients who develop EPS, pointing to progressive peritoneal fibrosis and sclerosis. The PAI-1 appearance rate has fair discriminative capacity from 3 years prior to EPS diagnosis. Therefore, effluent PAI-1 may aid in monitoring peritoneal fibrosis and serve as a biomarker for EPS.
Insights
Elevated levels of plasminogen activator inhibitor 1 (PAI-1) in peritoneal dialysis fluid may indicate progressive peritoneal fibrosis. This biomarker shows fair discriminative capacity for identifying patients who will develop encapsulating peritoneal sclerosis (EPS) years before diagnosis.
Area of Science:
- Nephrology
- Biomarker Discovery
- Peritoneal Dialysis Research
Background:
- Peritoneal fibrosis is a complication of peritoneal dialysis (PD).
- Matrix metalloproteinase 2 (MMP-2) and plasminogen activator inhibitor 1 (PAI-1) have been suggested as biomarkers for peritoneal fibrosis.
- This study investigates MMP-2 and PAI-1 as early diagnostic markers for encapsulating peritoneal sclerosis (EPS) in PD patients.
Purpose of the Study:
- To evaluate effluent MMP-2 and PAI-1 as early diagnostic markers for EPS.
- To assess the predictive value of these biomarkers in the years preceding EPS diagnosis.
Main Methods:
- A case-control study comparing PD patients who developed EPS with controls.
- Dialysate samples were analyzed for MMP-2 and PAI-1 appearance rates.
- EPS diagnosis was confirmed by expert nephrologists and a radiologist.
Main Results:
- No significant difference in MMP-2 appearance rates was found between EPS cases and controls up to 4 years before diagnosis.
- PAI-1 appearance rates were significantly higher in patients who developed EPS (P=0.01).
- PAI-1 showed fair discriminative ability (AUC=0.77) for EPS prediction at 1 year prior to diagnosis.
Conclusions:
- Elevated effluent PAI-1 levels are associated with progressive peritoneal fibrosis and EPS development.
- Effluent PAI-1 may serve as a valuable biomarker for monitoring peritoneal fibrosis and aiding in early EPS diagnosis.
- Further validation is needed due to the low event rate of EPS in this single-center study.

