The effect of different immunosuppressive regimens on TGF-beta1 expression in kidney transplant patients.
Transforming growth factor (TGF)-beta1 is a key profibrogenic cytokine associated with the pathogenesis of chronic allograft nephropathy (CAN). The primary aim of this study was to evaluate TGF-beta1 expression in protocol kidney graft biopsy in patients treated with different immunosuppressive regimens. Protocol kidney graft biopsies were carried out in 77 patients with stable graft function at 1 year after kidney transplantation, treated with a triple-drug regimen based on cyclosporin A (CyA; n = 49) or tacrolimus (TAC; n = 28). Morphological findings were assessed using the Banff 97 classification. TGF-beta1 expression was analysed using immunochemistry, and semiquantitatively scored in different renal structures (total score 0-18). Clinical data were analysed at the time of biopsy, and 12 months thereafter. No significant relation was found between the used immunosuppressive regimen and the histomorphological picture in the graft. TGF-beta1 expression within graft tissue was significantly higher in patients treated with CyA when compared with TAC (9.94 +/- 4.2 vs. 5.0 +/- 3.2; P < 0.001). Serum creatinine and glomerular filtration rate (GFR; Cockroft-Gault calculation) were comparable in both groups but, in the course of the next 12 months, GFR significantly decreased only in the CyA-treated group (from 1.03 +/- 0.33 to 0.96 +/- 0.37 ml/s) while not changing in the TAC-treated group. Patients treated with TAC had significantly lower diastolic blood pressure and serum cholesterol. The significantly lower TGF-beta1 expression in 1-year protocol kidney graft biopsy in TAC-treated patients with stable renal function, and the different development of graft function in both groups suggest a possible benefit of TAC for long-term graft acceptance.
Matl
Ivo
I
Department of Nephrology, Transplant Center Institute for Clinical and Experimental Medicine, Prague, Czech Republic. ivo.matl@medicon.cz
Viklický
Ondrej
O
Voska
Ludek
L
Lodererová
Alena
A
Vítko
Stefan
S
D000328:Adult; D000368:Aged; D001706:Biopsy; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007668:Kidney / Q000737:chemistry / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage; D016212:Transforming Growth Factor beta / Q000032:analysis*; D053773:Transforming Growth Factor beta1; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016572:Cyclosporine; D016559:Tacrolimus