Risk factors for capillary C4d deposition in kidney allografts: evaluation of a large study cohort

Transplantation. 2004 Aug 15;78(3):447-52. doi: 10.1097/01.tp.0000128344.94808.03.


Background: Capillary deposition of the complement split product C4d has turned out to be a valuable marker of antibody-mediated rejection. The impact of pre- and posttransplant variables including particular immunosuppressive regimens on the frequency of C4d deposition has not yet been systematically investigated in a large multivariate analysis.

Methods: In this retrospective study, the authors evaluated the incidence of C4d deposition in 388 kidney transplant recipients subjected to diagnostic biopsy within the first 6 months and analyzed the influence of potential confounders on the rate of C4d-positive graft dysfunction by applying multivariate logistic regression.

Results: Sixty-six recipients (17%) developed linear C4d deposits in at least a quarter of peritubular capillaries, a finding associated with inferior 1-year allograft survival (73% vs. 88% in C4d-negative patients, P=0.0003). A 50% reduction in the odds of C4d-positive graft dysfunction was found if calcineurin inhibitor or mycophenolate mofetil (MMF) therapy was started 2 to 4 hr before transplantation when compared with initiation after surgery (adjusted odds ratio [OR], 0.5; P=0.03). No differences with respect to C4d staining results were found for the use of tacrolimus, MMF, or sirolimus, or for cyclosporine C2 monitoring. Retransplantation (OR, 3.6; P<0.001) and presensitization (OR, 3.1; P=0.002) turned out to be strong independent risk factors for C4d deposition.

Conclusions: The authors' results suggest a reduced risk of C4d-positive graft dysfunction for patients receiving immunosuppression before transplantation. Apart from first dose timing, no influence of particular immunosuppressive strategies on C4d staining results was found.

MeSH terms

  • Adult
  • Biopsy
  • Cadaver
  • Capillaries
  • Cohort Studies
  • Complement C4 / analysis*
  • Complement C4b*
  • Confidence Intervals
  • Drug Therapy, Combination
  • Graft Rejection / epidemiology*
  • Graft Survival / physiology*
  • Histocompatibility Testing
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / mortality
  • Kidney Transplantation / pathology*
  • Living Donors
  • Middle Aged
  • Odds Ratio
  • Peptide Fragments / analysis*
  • Retrospective Studies
  • Risk Factors
  • Survival Analysis
  • Tissue Donors / statistics & numerical data
  • Transplantation, Homologous / pathology


  • Complement C4
  • Immunosuppressive Agents
  • Peptide Fragments
  • Complement C4b
  • complement C4d