title: C4d complement split product in diagnosis of immunological activity of chronic allograft nephropathy.
abstract: BACKGROUND
  Activation of the humoral branch of the immunological response is currently believed to play an important role in pathogenesis of chronic allograft nephropathy. The impact of humoral alloreactivity, indicated by the presence of C4d deposits in peritubular capillaries of a renal allograft, on the development of chronic allograft nephropathy is a significant problem in transplantation. The aim of the study was to assess and correlate C4d expression in patients with chronic allograft nephropathy, with clinical and morphological variables, as well as to assess the impact of a change in immunosuppression regimen on posttransplant course and renal allograft morphology.
  
  
  METHODS
  Twenty-six patients with chronic allograft nephropathy underwent biopsies to correlate C4d expression with clinical parameters and morphological findings. In all patients azathioprine was replaced with mycophenolate mofetil with additional CsA dose reduction in 12 patients. After 1 year, 14 protocol biopsies were performed.
  
  
  RESULTS
  The frequency of C4d peritubular capillary deposition among patients with chronic allograft nephropathy was 30%. C4d expression appeared later after transplantation, was correlated with chronic allograft glomerulopathy and proteinuria but not other clinical or histological variables. C4d deposits displayed no independent impact on serum creatinine level. Proteinuria was significantly more reduced in the C4d(+) group. Progression of chronic morphological changes was significantly accelerated in the C4d(+) group.
  
  
  CONCLUSIONS
  C4d peritubular capillary expression did not differentiate patients after immunosuppression enhancement, but it predisposed to progression of chronic morphological findings during 1-year observation.
authors.affiliation: Department of Transplant Medicine and Nephrology, Transplantation Institute, Warsaw Medical University, ul. Nowogrodzka 59, 02-006 Warsaw, Poland. andrewcio@poczta.wp.pl
authors.forename: A
authors.initials: A
authors.lastname: Mroz
authors.forename: Z
authors.initials: Z
authors.lastname: Lewandowski
authors.forename: T
authors.initials: T
authors.lastname: Cieciura
authors.forename: B
authors.initials: B
authors.lastname: Matłosz
authors.forename: J
authors.initials: J
authors.lastname: Pazik
authors.forename: A
authors.initials: A
authors.lastname: Kwiatkowski
authors.forename: J
authors.initials: J
authors.lastname: Szmidt
authors.forename: M
authors.initials: M
authors.lastname: Durlik
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002196:Capillaries / Q000473:pathology; D002908:Chronic Disease; D015935:Complement C4b / Q000032:analysis*; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000453:epidemiology; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D007684:Kidney Tubules / Q000473:pathology; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d; D003404:Creatinine