title: Early short-term imatinib treatment is sufficient to prevent the development of chronic allograft nephropathy.
abstract: BACKGROUND
  Chronic allograft nephropathy (CAN), now defined as interstitial fibrosis and tubular atrophy not otherwise specified, is a near universal finding in kidney grafts by the end of the first decade posttransplantation. Platelet-derived growth factor (PDGF) is a major mitogen mediating mesenchymal cell proliferation in CAN. Here, we investigated whether early short-term PDGF inhibition with imatinib could prevent CAN.
  
  
  METHODS
  Kidney transplantations were performed from Dark-Agouti (DA) to Wistar-Furth (WF) rats and syngenic controls were done between DA rats. Allografts were immunosuppressed with cyclosporine. One group was also treated with imatinib for the first 30 days after transplantation. Serum creatinine levels were measured once a week. Grafts were harvested 90 days after transplantation.
  
  
  RESULTS
  In control allografts, moderate to intense chronic changes were seen, whereas in syngenic grafts, no changes were seen. The early imatinib treatment prevented the development of CAN significantly compared to control allografts. Only few histological changes were seen. Fibrogenic growth factor ligand and receptor induction as well as inflammatory cell response was significantly inhibited by imatinib. Creatinine values of imatinib-treated allografts were also significantly lower compared to controls.
  
  
  CONCLUSIONS
  We show that short-term imatinib treatment is sufficient to prevent CAN significantly, indicating that early PDGF induction has an important role in the pathogenesis of CAN. Here, we provide preclinical work that will need to be confirmed in patients with CAN.
authors.affiliation: Transplantation Laboratory, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland. johanna.savikko@helsinki.fi
authors.forename: Johanna
authors.initials: J
authors.lastname: Savikko
authors.forename: Jukka M
authors.initials: JM
authors.lastname: Rintala
authors.forename: Sini E
authors.initials: SE
authors.lastname: Rintala
authors.forename: Petri K
authors.initials: PK
authors.lastname: Koskinen
authors.forename: Eva
authors.initials: E
authors.lastname: von Willebrand
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D002908:Chronic Disease; D016572:Cyclosporine / Q000627:therapeutic use; D000068877:Imatinib Mesylate; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016030:Kidney Transplantation; D008297:Male; D010879:Piperazines / Q000627:therapeutic use*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D007166:Immunosuppressive Agents; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D011743:Pyrimidines; D016572:Cyclosporine; D000068877:Imatinib Mesylate