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.