Rituximab Rescue for Refractory Antibody Mediated Rejection after Kidney Transplantation

Lee, Samuel; Joo, Sun Hyung; Kim, Joo Seop; Goldstein, Michael J; Cohen, David J; Hardy, Mark A

Abstract

PURPOSE
Antibody mediated rejection (AMR), although less common than acute cellular rejection (ACR), may be recalcitrant to conventional rescue therapy. AMR is caused by de novo B-cell mediated production of immunoglobulin G antibody (IgG) targeted against specific allograft antigen in a presensitized recipient. Rituximab is a chimeric murine- human anti-CD20 monoclonal antibody which targets CD-20 positive B-cells for elimination. Rituximab has been described to improve allograft salvage for refractory AMR.
METHODS
From January 2002 to May 2004, 11 patients were diagnosed with AMR. The first 5 patients (non-rituximab group: NRG) were treated with high dose steroids, plasmapheresis followed by IVIG (500 mg/kg/dose) in addition to OKT3 and/or rabbit antithymocyte globulin. The latter 6 patients (rituximab group: RG) were given Rituximab (375 mg/m2) with IVIG following plasmapheresis. All patients had biopsy proven AMR.
RESULTS
Four patients received allografts from living donors and one patient from cadaveric donor in NRG. Each three patients received allografts from living or cadaveric donors in RG. One patient of RG had a positive anti-HLA B-cell crossmatch by CDC (complement dependent cytotoxicity). The anti-donor antibody was reduced to zero with negative CDC and flowcytometry through a desensitization protocol prior to transplantation. The time to diagnosis of AMR in both groups were 17.8+/-18.17 days (NRG); 11+/-2.5 days (RG). ACR was identified in conjunction with AMR in 2 (40%: NRG), 4 patients (66.7%: RG), respectively. All patients had biopsies with classic features of AMR on light microscopy, including C4d staining. Three (50%) patients of RG had positive post-transplantation CDC and donor-specific antibody (DSA) identified. Mean serum creatinine (SCr) upon diagnosis of AMR were 4.3+/-1.71 mg/dL (NRG); 5.77+/-2.65 mg/dL (RG). The rescue rate of RG was superior than NRG (83% vs. 40%, P>0.05). The time to rescue from AMR in both groups were 40.5 +/-28.99 days (NRG); 48+/-54.67 days (RG). Mean SCr of the rescued patients were 1.65+/-0.07 mg/dL (NRG); 2.2+/-1.4 (RG) with median follow up of 120 days (range 33~319 days). Allograft nephrectomies were performed in 3 patients of NRG.
CONCLUSION
Rescue therapy with Rituximab improves allograft salvage after AMR and should be considered early in the treatment of biopsy proven AMR.