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  • Title: Different effects of tacrolimus and cyclosporine on PDGF induction and chronic allograft injury: evidence for improved kidney graft outcome.
    Author: Savikko J, Teppo AM, Taskinen E, von Willebrand E.
    Journal: Transpl Immunol; 2014 Sep; 31(3):145-51. PubMed ID: 25158212.
    Abstract:
    INTRODUCTION: 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. MATERIALS AND 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. DISCUSSION: 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.
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