title: Serum TGF-beta1 correlates with chronic histopathological lesions in protocol biopsies of kidney allograft recipients.
abstract: BACKGROUND
  Transforming growth factor-beta (TGF-beta) 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-beta levels and histological changes in protocol biopsies of kidney allograft recipients.
  
  
  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 C2 levels), MMF, prednisone, and no daclizumab (n = 21).
  
  
  METHODS
  In both groups we performed histological assessments (Banff 97) and measured serum TFG-beta levels before as well as, at 3 and 12 months after transplantation.
  
  
  RESULTS
  We found a relationship between immunosuppressive regimen and the TGF-beta concentration over 1 year of observation. Before transplant the TGF-beta1 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-beta1 concentrations were significantly higher among group B than A. We conclude that TGF-beta1 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.
authors.affiliation: Warsaw Medical School, Warsaw, Poland. tbaczkowska@wp.pl
authors.forename: T
authors.initials: T
authors.lastname: Baczkowska
authors.forename: A
authors.initials: A
authors.lastname: Perkowska-Ptasińska
authors.forename: A
authors.initials: A
authors.lastname: Sadowska
authors.forename: Z
authors.initials: Z
authors.lastname: Lewandowski
authors.forename: E
authors.initials: E
authors.lastname: Nowacka-Cieciura
authors.forename: T
authors.initials: T
authors.lastname: Cieciura
authors.forename: J
authors.initials: J
authors.lastname: Pazik
authors.forename: D
authors.initials: D
authors.lastname: Lewandowska
authors.forename: A
authors.initials: A
authors.lastname: Mroz
authors.forename: A
authors.initials: A
authors.lastname: Urbanowicz
authors.forename: S
authors.initials: S
authors.lastname: Nazarewski
authors.forename: R
authors.initials: R
authors.lastname: Danielewicz
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016572:Cyclosporine / Q000627:therapeutic use; D000077561:Daclizumab; D004359:Drug Therapy, Combination; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000473:pathology*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies; D015203:Reproducibility of Results; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000097:blood*; D053773:Transforming Growth Factor beta1; D014184:Transplantation, Homologous / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016572:Cyclosporine; D000077561:Daclizumab; D009173:Mycophenolic Acid; D011241:Prednisone