Treatment of chronic renal allograft rejection in rats with a low-molecular-weight heparin (reviparin)

Background, Low-molecular-weight heparin (LMWH) has been shown to prolong s urvival of rat cardiac allografts independently from immunosuppressive trea tment. Furthermore, long-term treatment reduces the development of chronic graft vascular disease after experimental heart transplantation. The aim of the present study was to determine whether treatment with the LMWH revipar in has a beneficial effect on chronic rejection in a rat renal allograft; m odel. Methods. Kidneys of Fisher (F344) rats were transplanted into unilaterally nephrectomized Lewis (LEW) recipients. LEW --> LEW isografts served as cont rols. Animals were treated with cyclosporine (5 mg/kg/d) for the first 10 d ays. Nephrectomy of the remaining kidney was performed after 10 days. Allog rafted animals were treated either with reviparin (2 mg/kg/d subcutaneously ) for 24 weeks (Allo-24), from week 12 to 24 (Allo-12), or with vehicle for 24 weeks. Proteinuria was determined at regular intervals. Kidneys were ha rvested after 24 weeks for histomorphological and immunohistochemical evalu ation. Results. No major bleeding complications were observed in reviparin-treated animals. Proteinuria was significantly reduced in allografted animals both by early as well as by late-onset treatment with reviparin. Transplant glo merulopathy was diminished in Allo-24 and in Allo-12 groups compared to veh icle-treated animals, whereas tubulointerstitial inflammation was influence d only in animals immediately treated with reviparin. Immunohistochemical. studies demonstrated a marked reduction of renal monocyte and T-cell infilt ration as well as expression of MHC II by treatment with reviparin. Conclusions. Treatment with the LMWH reviparin significantly improved chron ic renal allograft rejection in the F344-to-LEW rat model, both after early and late start of therapy. Although the exact mechanisms of this beneficia l effect remain unclear, our data offer a potential new therapeutical appro ach for prevention of chronic allograft nephropathy.