title: Higher Dialysate Matrix Metalloproteinase-2 Levels Are Associated with Peritoneal Membrane Dysfunction.
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). ♦
  
  
  CONCLUSIONS
  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.affiliation: Department of Renal Medicine, Princess Alexandra Hospital, Brisbane, Australia School of medicine, University of Queensland, Brisbane, Australia Translational Research Institute, Brisbane, Australia.
authors.forename: Yeoungjee
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Department of Renal Medicine, Princess Alexandra Hospital, Brisbane, Australia School of medicine, University of Queensland, Brisbane, Australia Translational Research Institute, Brisbane, Australia david.johnson2@health.qld.gov.au.
authors.forename: David W
authors.initials: DW
authors.lastname: Johnson
authors.affiliation: Department of Renal Medicine, Princess Alexandra Hospital, Brisbane, Australia School of medicine, University of Queensland, Brisbane, Australia Translational Research Institute, Brisbane, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Vesey
authors.affiliation: Department of Renal Medicine, Princess Alexandra Hospital, Brisbane, Australia School of medicine, University of Queensland, Brisbane, Australia Translational Research Institute, Brisbane, Australia.
authors.forename: Carmel M
authors.initials: CM
authors.lastname: Hawley
authors.affiliation: School of medicine, University of Queensland, Brisbane, Australia.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Pascoe
authors.affiliation: Fresenius Medical Care, Sydney, Australia.
authors.forename: Margaret
authors.initials: M
authors.lastname: Clarke
authors.affiliation: Institute of Translation, Innovation, Methodology and Engagement, Cardiff, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Topley
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis; D005260:Female; D015312:Hemodialysis Solutions / Q000737:chemistry*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D008875:Middle Aged; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000503:physiopathology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis
chemical_list: D015415:Biomarkers; D015312:Hemodialysis Solutions; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2
keywords: Biocompatible; glucose degradation products; matrix metalloproteinase-2; peritoneal dialysis; peritoneal solute transport rate; peritonitis; tissue inhibitor of metalloproteinase-1