Risk factors for capillary C4d deposition in kidney allografts: evaluation of a large study cohort.
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.
Lorenz
Matthias
M
Department of Internal Medicine III, University of Vienna, Vienna, Austria.
Regele
Heinz
H
Schillinger
Martin
M
Exner
Markus
M
Rasoul-Rockenschaub
Susanne
S
Wahrmann
Markus
M
Kletzmayr
Josef
J
Silberhumer
Gerd
G
Hörl
Walter H
WH
Böhmig
Georg A
GA
D000328:Adult; D001706:Biopsy; D002102:Cadaver; D002196:Capillaries; D015331:Cohort Studies; D003181:Complement C4 / Q000032:analysis*; D015935:Complement C4b; D016001:Confidence Intervals; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000453:epidemiology*; D006085:Graft Survival / Q000502:physiology*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D019520:Living Donors; D008875:Middle Aged; D016017:Odds Ratio; D010446:Peptide Fragments / Q000032:analysis*; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D014019:Tissue Donors / Q000706:statistics & numerical data; D014184:Transplantation, Homologous / Q000473:pathology
D003181:Complement C4; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d