title: Can effluent matrix metalloproteinase 2 and plasminogen activator inhibitor 1 be used as biomarkers of peritoneal membrane alterations in peritoneal dialysis patients?
abstract: BACKGROUND
  Peritoneal effluent contains clinically relevant substances derived from intraperitoneal production or transperitoneal transport, or both. The glycoproteinase matrix metalloproteinase 2 (MMP-2) cleaves denatured collagen and complements other collagenases in the degradation of fibrillar collagens. Elevated intraperitoneal levels of plasminogen activator inhibitor 1 (PAI-1) have been demonstrated to be present in patients with intra-abdominal adhesions. The aim of the present study was therefore to investigate the potential for effluent MMP-2 and PAI-1 to be used as markers of the development of peritoneal alterations. In addition, MMP-2 was analyzed in previously frozen effluent samples from a uremic rat model, in which data concerning the severity of peritoneal fibrosis were available.
  
  
  METHODS
  This prospective, single-center cohort study included 86 incident peritoneal dialysis (PD) patients. All patients were treated solely with biocompatible dialysis solutions and underwent a standard peritoneal permeability analysis (SPA). The presence of local MMP-2 and PAI-1 production and the relationships between those markers and peritoneal transport parameters were analyzed. Furthermore, effluent interleukin 6 was analyzed as a marker of local inflammation.
  
  
  RESULTS
  Median effluent levels of 21.4 ng/mL for MMP-2 and 0.9 ng/mL for PAI-1 were found. The median dialysate appearance rates were 218.8 ng/min for MMP-2 and 9.6 ng/min for PAI-1. Local peritoneal production averaged 90% of effluent MMP-2 concentration and 74% of effluent PAI-1 concentration. Furthermore, correlations between peritoneal transport parameters and MMP-2 and PAI-1 were observed. Longitudinal follow-up showed no change for MMP-2 (p = 0.37), but a tendency for PAI-1 to increase with the duration of PD (p < 0.001). In rats, a significant relationship was present between the extent of peritoneal fibrosis and the appearance rate of MMP-2 (r = 0.64, p = 0.03).
  
  
  CONCLUSIONS
  The foregoing data illustrate the potential of effluent MMP-2 and PAI-1 as biomarkers of peritoneal modifications, especially fibrosis; however, the components of peritoneal transport and local production should be clearly distinguished in every patient.
authors.affiliation: Division of Nephrology,1 Department of Internal Medicine, Academic Medical Center, University of Amsterdam, and Dianet Foundation,2 Amsterdam-Utrecht, Netherlands.
authors.forename: Deirisa Lopes
authors.initials: DL
authors.lastname: Barreto
authors.forename: Annemieke M
authors.initials: AM
authors.lastname: Coester
authors.forename: Dirk G
authors.initials: DG
authors.lastname: Struijk
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Krediet
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D056627:Peritoneal Fibrosis / Q000201:enzymology* / Q000209:etiology; D010537:Peritoneum / Q000378:metabolism*; D010539:Permeability; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D011446:Prospective Studies; D051381:Rats; D055815:Young Adult
chemical_list: D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D020778:Matrix Metalloproteinase 2
keywords: Biomarkers; fibrosis; matrix metalloproteinase 2; peritoneal membrane; plasminogen activator inhibitor type 1