Combined posttransplant prophylactic IVIg/anti-CD 20/plasmapheresis in kidney recipients with preformed donor-specific antibodies: a pilot study.
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).


CONCLUSIONS
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.
Loupy
Alexandre
A
INSERM, U970, Paris Cardiovascular Research Center PARCC, Paris, France. alexandreloupy@gmail.com
Suberbielle-Boissel
Caroline
C
Zuber
Julien
J
Anglicheau
Dany
D
Timsit
Marc-Olivier
MO
Martinez
Frank
F
Thervet
Eric
E
Bruneval
Patrick
P
Charron
Dominique
D
Hill
Gary S
GS
Nochy
Dominique
D
Legendre
Christophe
C
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology*; D065095:Calcineurin Inhibitors; D003131:Combined Modality Therapy; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008833:Microcirculation; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010865:Pilot Projects; D010956:Plasmapheresis / Q000379:methods*; D011183:Postoperative Complications / Q000453:epidemiology; D012189:Retrospective Studies; D018570:Risk Assessment; D000069283:Rituximab; D014019:Tissue Donors / Q000706:statistics & numerical data
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D065095:Calcineurin Inhibitors; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D000069283:Rituximab; D009173:Mycophenolic Acid