Conversion from Cyclosporin a to Sirolimus Retards the Progression of Chronic Allograft Nephropathy in the Long Term in a Rat Kidney Transplantation Model

Abstract

In a rat renal allograft model, the long-term effect of conversion from cyclosporin A (CsA) to sirolimus on recipient kidneys and growth factor expression were compared with continuous use or withdrawal of CsA. Kidneys from Fisher 344 rats were orthotopically transplanted into Lewis rats. Four Fisher 344 to Lewis allograft groups were treated post-transplant as follows: (i) CsA (transplant to week 8) then sirolimus (weeks 8 - 24); (ii) CsA (transplant to week 24); (iii) CsA (transplant to week 8) then vehicle (weeks 8 - 24); (iv) control vehicle (transplant to week 24). A fifth group underwent syngeneic isograft (Lewis to Lewis) with no drug treatment. Proteinuria was measured every 4 weeks and grafts harvested at 24 weeks for morphological and immunohistochemical analysis. Conversion from CsA to sirolimus resulted in a significant decrease in proteinuria at 24 weeks, a lower Banff sum score and lower expression of transforming growth factor mRNA compared with continuous use or withdrawal of CsA. In conclusion, conversion from CsA to sirolimus retarded progression of chronic allograft nephropathy in the rat model.