title: Increased C4d in post-reperfusion biopsies and increased donor specific antibodies at one-week post transplant are risk factors for acute rejection in mild to moderately sensitized kidney transplant recipients.
abstract: In order to define the intensity of immunosuppression, we examined risk factors for acute rejection in desensitization protocols that use baseline donor-specific antibody levels measured as mean fluorescence intensity (MFImax). The study included 146 patients transplanted with a negative flow crossmatch and a mean follow-up of 18 months with the majority (83%) followed for at least 1 year. At the time of transplant, mean-calculated panel-reactive antibody and MFImax ranged from 10.3-57.2% and 262-1691, respectively, between low- and high-risk protocols. Mean MFImax increased significantly from transplant to 1 week and 1 year. The incidence of acute rejection (mean 1.65 months) as a combination of clinical and subclinical rejection was 32%, including 14% cellular, 12% antibody-mediated, and 6% mixed rejection. In regression analyses, only C4d staining in post-reperfusion biopsies (hazard ratio 3.3, confidence interval 1.71-6.45) and increased specific antibodies at 1-week post transplant were significant predictors of rejection. A rise in MFImax by 500 was associated with a 2.8-fold risk of rejection. Thus, C4d staining in post-reperfusion biopsies and an early rise in donor specific antibodies after transplantation are risk factors for rejection in moderately sensitized patients.
authors: Department of Surgery, University of Wisconsin, Madison, Wisconsin 51703, USA. axd@medicine.wisc.edu
authors: Arjang
authors: A
authors: Djamali
authors: Brenda L
authors: BL
authors: Muth
authors: Thomas M
authors: TM
authors: Ellis
authors: Maha
authors: M
authors: Mohamed
authors: Luis A
authors: LA
authors: Fernandez
authors: Karen M
authors: KM
authors: Miller
authors: Janet M
authors: JM
authors: Bellingham
authors: Jon S
authors: JS
authors: Odorico
authors: Joshua D
authors: JD
authors: Mezrich
authors: John D
authors: JD
authors: Pirsch
authors: Tony M
authors: TM
authors: D'Alessandro
authors: Vijay
authors: V
authors: Vidyasagar
authors: R Michael
authors: RM
authors: Hofmann
authors: Jose R
authors: JR
authors: Torrealba
authors: Dixon B
authors: DB
authors: Kaufman
authors: David P
authors: DP
authors: Foley
mesh_terms: D000208:Acute Disease; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016009:Chi-Square Distribution; D015935:Complement C4b / Q000378:metabolism*; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood*; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000378:metabolism*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D014019:Tissue Donors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d