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

Arjang Djamali, Brenda L Muth, Thomas M Ellis, Maha Mohamed, Luis A Fernandez, Karen M Miller, Janet M Bellingham, Jon S Odorico, Joshua D Mezrich, John D Pirsch, Tony M D'Alessandro, Vijay Vidyasagar, R Michael Hofmann, Jose R Torrealba, Dixon B Kaufman, David P Foley, Arjang Djamali, Brenda L Muth, Thomas M Ellis, Maha Mohamed, Luis A Fernandez, Karen M Miller, Janet M Bellingham, Jon S Odorico, Joshua D Mezrich, John D Pirsch, Tony M D'Alessandro, Vijay Vidyasagar, R Michael Hofmann, Jose R Torrealba, Dixon B Kaufman, David P Foley

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.

Figures

Figure 1. Changes in DSA after transplantation
Figure 1. Changes in DSA after transplantation
Panel a. The bar graph displays mean DSA levels (MFImax) early post transplant in all desensitization protocols. Panel b. The graph shows mean DSA levels in all patients throughout the first posttransplant year. DSA increased with time despite immunosuppression and desensitization. MFIsum class II was the primary cause of the rise in DSA.
Figure 2. Post-reperfusion biopsy and C4d staining
Figure 2. Post-reperfusion biopsy and C4d staining
Panel A. Percent patients in each protocol that underwent a post-reperfusion biopsy (blue bar) and % patients in each protocol that had positive C4d staining in the reperfusion biopsy (red bar). Actual numbers are displayed within the bars. Panel B. C4d staining by immunoperoxidase in a post-reperfusion biopsy (a) and in a pre-implantation control biopsy (b). Only some of the post-reperfusion biopsies were positive for C4d.
Figure 3. Kaplan-Meier survival curve for rejection…
Figure 3. Kaplan-Meier survival curve for rejection free probability in patients with or without post-reperfusion C4d staining
C4d (+) patients were at significantly greater risk for antibody-mediated or mixed rejection.

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Source: PubMed

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