Differential effects of cyclosporin and tacrolimus on the expression of fibrosis-associated genes in isolated glomeruli from renal transplants

Background: Chronic allograft nephropathy is characterized by an excessive accumulation of extracellular matrix proteins leading to glomerular and int erstitial fibrosis. The aim of this study was to determine the effects of t wo different immunosuppressive agents (cyclosporin and tacrolimus) on the e xpression of the genes controlling extracellular matrix deposition in renal transplant glomeruli. Methods: Fifty-one renal transplant recipients were randomized to receive i mmunosuppression with either microemulsion cyclosporin or tacrolimus. Isola ted glomeruli were plucked from protocol transplant biopsies performed 1 we ek, 3 months and 6 months after transplantation. Expression of the genes fo r collagen IV alpha2, collagen III, matrix metalloproteinase 2, tissue inhi bitor of metalloproteinases (TIMP) 1 and TIMP-2, tenascin and transforming growth factor (TGF) beta1 was studied by quantitative reverse transcriptase -polymerase chain reaction. Results: The expression of messenger RNA (mRNA) for collagen III and TIMP-1 was significantly higher in patients receiving cyclosporin therapy than in those having tacrolimus (P<0.01); this finding was accounted for by differ ences in the biopsy material at 1 week. A significant difference in collage n III, TIMP-1 and TIMP-2 mRNA expression was also detected between patients depending on the source of renal donor (cadaveric or living). There were n o significant differences in the level of glomerular TGF-<beta>1. Conclusion: The data provide new in vivo evidence that tacrolimus may exert a less fibrogenic influence on transplant glomeruli than cyclosporin.