Journal
TRANSPLANTATION
Volume 89, Issue 11, Pages 1403-1410Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0b013e3181da1cc3
Keywords
Anti CD-20; IVIg; Donor-specific antibodies; DSA; Kidney transplantation; Antibody-mediated rejection
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Background. This study assesses the immunologic, functional, and histologic course of kidney recipients with preformed donor-specific alloantibodies (DSA) receiving deceased donor kidneys according to two prophylactic strategies that have been sequentially applied posttransplant. Methods. The first strategy combined posttransplant quadritherapy/intravenous immunoglobulin (group 1, n = 36) and the second added to the above protocol anti-CD20/plasmapheresis (group 2, n = 18). All patients had a concomitant evaluation of glomerular filtration rate, protocol biopsies, and DSA mean intensity of fluorescence (MFI) at 3 month and 1 year posttransplant. Results. Peak and day-0 class-I or II DSAmax-MFI were similar in both groups. The rate of acute antibody-mediated rejection (AMR) was similar in both groups (19.6% vs. 16.6%, respectively). At 1 year posttransplant, group 2 was characterized by lower microcirculation inflammation lesions (glomerulitis + capilaritis score of 1.8 + /- 0.2 vs. 2.7 +/- 0.2, respectively, P = 0.03), a lower rate of transplant glomerulopathy (7% vs. 38%, P = 0.02), and a lower rate of chronic AMR (41.3% vs. 13.3%, respectively, P = 0.03). The decline in DSA-MFI from day 0 to 1 year was 44% +/- 13% in group 1 compared with 80% +/- 8% in group 2 (P = 0.02). Finally, the 1-year glomerular filtration rate was 43 +/- 16 vs. 54 +/- 16 mL/min/1.73 m(2) in groups 1 and 2, respectively (P = 0.04). Conclusion. This study raises the possibility that a more intensive day 0 prophylactic immunosuppressive strategy combining intravenous immunoglobulin/anti-CD20/plasmapheresis in this high-risk population, despite similar rates of early acute clinical humoral rejection, is associated with significant differences in long-term function and chronic AMR rate. Future prospective randomized studies are needed to assess the best strategies to be applied in light of the pretransplant immunologic risk stratification.
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