title: Different effects of tacrolimus and cyclosporine on PDGF induction and chronic allograft injury: evidence for improved kidney graft outcome.
abstract: BACKGROUND
  Chronic allograft injury is the most frequent cause of long-term kidney allograft loss. Cyclosporine (CsA) nephrotoxicity is an important factor contributing to graft loss. Increased fibrosis has been reported in renal transplants under CsA as compared with tacrolimus (Tac). Platelet-derived growth factor (PDGF) is a well-characterized fibrogenic growth factor in renal disease.
  
  
  OBJECTIVE
  Here we investigated the effect of Tac on kidney grafts and PDGF expression both early after transplantation as well as during long-term follow-up of rat renal allografts, and compared it to CsA. Tac and CsA were also studied on PDGF secretion in macrophages in vitro.
  
  
  METHODS
  Kidney allografts were immunosuppressed with Tac or CsA. Grafts were analyzed by histology and immunohistochemistry. ELISA was used to measure PDGF-levels in Tac and CsA-treated macrophage cultures.
  
  
  RESULTS
  Tac ameliorated markedly both acute and chronic changes, whereas moderate to intense histological changes were seen in CsA-treated allografts. Tac also significantly inhibited PDGF expression compared to CsA. At clinically adjusted concentration CsA induced PDGF in macrophages whereas Tac did not.
  
  
  CONCLUSIONS
  Tac may be less fibrogenic than CsA by decreasing PDGF expression in kidney grafts as well as in macrophages. Data presented here suggests that decreased PDGF induction by Tac may be beneficial for later outcome of the kidney graft.
authors.affiliation: Transplantation Laboratory, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 3 (PO Box 21), 00014 Helsinki, Finland; Transplantation and Liver Surgery Unit, Helsinki University Central Hospital, Haartmaninkatu 4 (PO Box 340), 00029 HUS, Helsinki, Finland. Electronic address: johanna.savikko@helsinki.fi.
authors.forename: Johanna
authors.initials: J
authors.lastname: Savikko
authors.affiliation: Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Haartmaninkatu 4 (PO Box 372), 00029 HUS, Helsinki, Finland.
authors.forename: Anna-Maija
authors.initials: AM
authors.lastname: Teppo
authors.affiliation: Transplantation Laboratory, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 3 (PO Box 21), 00014 Helsinki, Finland.
authors.forename: Eero
authors.initials: E
authors.lastname: Taskinen
authors.affiliation: Transplantation Laboratory, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 3 (PO Box 21), 00014 Helsinki, Finland.
authors.forename: Eva
authors.initials: E
authors.lastname: von Willebrand
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002908:Chronic Disease; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D005355:Fibrosis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000187:drug effects; D006084:Graft Rejection / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D007165:Immunosuppression Therapy; D007668:Kidney / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016030:Kidney Transplantation; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011920:Rats, Inbred WF; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects; D014184:Transplantation, Homologous
chemical_list: D010982:Platelet-Derived Growth Factor; D016572:Cyclosporine; D016559:Tacrolimus
keywords: Chronic allograft injury; Cyclosporine; Kidney transplantation; Platelet-derived growth factor; Tacrolimus