Active TGF-beta1 expression in kidney transplantation: a comparative study of cyclosporin-A (CyA) and tacrolimus (FK506).

Chronic rejection is a major cause of graft dysfunction following kidney transplantation. This fibroproliferative disease may be promoted by overproduction of transforming growth factor beta (TGF-beta). Previous studies have suggested that cyclosporin-A (CyA) might increase production of this growth factor. The current study was designed to measure the expression of TGF-beta in renal transplant biopsies from patients immunosuppressed with either CyA or tacrolimus. Paraffin-embedded renal biopsies were sectioned, dewaxed and incubated with primary antibody against active TGF-beta1 antibody. After washing, the sections were treated with secondary antibody conjugated with fluorescein isothiocyanate (FITC). In each case the sections were assessed by semi-quantitative scanning laser confocal microscopy. Biopsies from patients receiving CyA expressed significantly more active TGF-beta1 than biopsies from patients receiving tacrolimus (P < 0.0001, Mann-Whitney test). The increased level of active TGF-beta1 expression in renal biopsies of patients receiving CyA may indicate a mechanism of chronic rejection.