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.
Department of Internal Medicine III, University of Vienna, Vienna, Austria.
Matthias
M
Lorenz
Heinz
H
Regele
Martin
M
Schillinger
Markus
M
Exner
Susanne
S
Rasoul-Rockenschaub
Markus
M
Wahrmann
Josef
J
Kletzmayr
Gerd
G
Silberhumer
Walter H
WH
Hörl
Georg A
GA
Böhmig
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