Serum TGF-β1 Correlates With Chronic Histopathological Lesions in Protocol Biopsies of Kidney Allograft Recipients

Abstract

Introduction Transforming growth factor-β (TGF-β) is a well-known profibrotic factor playing a role in chronic kidney allograft nephropathy. Cyclosporine (CsA)-sparing immunosuppressive regimens may improve long-term graft function. Our aim was to study the influence of immunosuppressive treatment with versus without calcineurin inhibitors on serum TGF-β levels and histological changes in protocol biopsies of kidney allograft recipients. Patients and Methods In this prospective, randomized study of 42 low-rejection risk patients we randomized two groups: group A: mycophenolate mofetil (MMF), prednisone, daclizumab, and reduced CsA dose for 7 months (5 mg per kg per day) followed by complete withdrawal ( n = 21); and group B: normal CsA dose (10 mg per kg per day adjusted according to C 2 levels), MMF, prednisone, and no daclizumab ( n = 21). Methods In both groups we performed histological assessments (Banff 97) and measured serum TFG-β levels before as well as, at 3 and 12 months after transplantation. Results We found a relationship between immunosuppressive regimen and the TGF-β concentration over 1 year of observation. Before transplant the TGF-β1 levels did not differ between the groups ( P = .29); at 3 months they were 33 ± 9 vs 49 ± 15 pg per mL, respectively, in groups A and B ( P = .08), and at 12 months they were 39.5 ± 4 versus 55.5 ± 11 pg per mL, respectively, in groups A and B ( P = .03). Protocol biopsies at 12 months in group B showed chronic tubular lesions more pronounced than in group A. TGF-β1 concentrations were significantly higher among group B than A. We conclude that TGF-β1 concentration may predict the development of kidney graft fibrosis; early CsA withdrawal may achieve a reduction in chronic tubular and interstitial injury of cadaveric kidney allografts.