title: Urinary Metalloproteinases-9 and -2 and Their Inhibitors TIMP-1 and TIMP-2 are Markers of Early and Long-Term Graft Function After Renal Transplantation.
abstract: OBJECTIVE
  Renal ischemia-reperfusion (I-R) injury (IRI) is an inseparable feature of organ transplantation and may have a negative impact on the graft, its function and survival. Acute tubular necrosis, which is reversible thanks to the regenerative capacity of renal tubular epithelial cells, is the main cause of acute renal failure secondary to IRI. MMP-2 and MMP-9 are proteolytic enzymes involved in digesting proteins that are components of the extracellular matrix (ECM) and the basement membrane of the nephrons. This way post-reperfusion MMP activation allows the inflammatory process to spread.
  
  
  METHODS
  In our studies, we focused on identifying whether the concentrations of MMP-2 and MMP-9 and their natural inhibitors TIMP-1 and TIMP-2 in urine sample at day 1 and day 30 as well as after 12 months following renal transplantation are markers of early and long-term renal function during meanly five-years observation. Moreover, in urine sampled at months 6 and 12 after renal transplantation, we determined the content of TGF-β as a graft fibrosis indicator.
  
  
  RESULTS
  MMP-9 concentration in the early post-transplant period is a major marker of early and long-term function of the transplanted kidney. Its increased concentration was correlated with lesions related to tubular atrophy and fibrosis in renal biopsies performed at months 3 and 12 after transplantation. Its concentration is correlated with TGF-β content in a later period.
  
  
  CONCLUSIONS
  TIMP-1 and-2 are primarily markers of an early function of the transplanted kidney. Early post-transplant concentration of MMP-2 is a marker of proteinuria in early and long-term post-transplant periods.
authors.affiliation: Clinical Department of Nephrology, Transplantology and Internal Medicine Pomeranian Medical University, Szczecin, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Kwiatkowska
authors.forename: Leszek
authors.initials: L
authors.lastname: Domanski
authors.forename: Joanna
authors.initials: J
authors.lastname: Bober
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Safranow
authors.forename: Maciej
authors.initials: M
authors.lastname: Romanowski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pawlik
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kwiatkowski
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Ciechanowski
mesh_terms: D001284:Atrophy; D015415:Biomarkers / Q000652:urine; D005355:Fibrosis; D005500:Follow-Up Studies; D006085:Graft Survival; D006801:Humans; D016030:Kidney Transplantation; D020778:Matrix Metalloproteinase 2 / Q000652:urine*; D020780:Matrix Metalloproteinase 9 / Q000652:urine*; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000652:urine*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000652:urine*
chemical_list: D015415:Biomarkers; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9