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Addition of Plasmapheresis Decreases the Incidence of Acute Antibody-Mediated Rejection in Sensitized Patients with Strong Donor-Specific Antibodies

Enver Akalin^*,, Rajani Dinavahi^*,, Rex Friedlander, Scott Ames, Graciela de Boccardo^*,, Vinita Sehgal^*,, Bernd Schröppel^*,, Madhu Bhaskaran^*,, Susan Lerner, Marileno Fotino, Barbara Murphy^*,, and Jonathan S. Bromberg

^* Renal Division, Recanati/Miller Transplantation Institute, Mount Sinai School of Medicine, Immunogenetics Laboratory, Rogosin Institute, and Renal Division and Transplant Services, North Shore University Hospital, New York, New York

Correspondence: Dr. Enver Akalin, Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1104, New York, NY 10029-6574. Phone: 212-659-8086; Fax: 212-348-2474; E-mail: enver.akalin{at}msnyuhealth.org

Background and objectives: The objective of this study was to investigate the effects of desensitization protocols using intravenous Ig with or without plasmapheresis in patients with donor-specific anti-HLA antibodies on prevention of antibody-mediated rejection and downregulation of donor-specific antibodies.

Design, setting, participants, & measurements: Thirty-five complement-dependent cytotoxicity T cell cross-match–negative but complement-dependent cytotoxicity B cell and/or flow cytometry cross-match–positive kidney transplant recipients were treated with high-dosage intravenous Ig plus Thymoglobulin induction treatment. Donor-specific antibody strength was stratified as strong, medium, or weak by Luminex flow beads. Group 1 patients had weak/moderate and group 2 strong donor-specific antibodies

Results: Whereas no group 1 patients had acute rejection, 66% of group 2 had acute rejection (44% antibody-mediated rejection, 22% cellular rejection). The protocol was then changed to the addition of peritransplantation plasmapheresis to patients with strong donor-specific antibodies (group 3). This change resulted in a dramatic decrease in the acute rejection rate to 7%. During a median 18 mo of follow-up, patient survival was 100, 100, and 93% and graft survival was 100, 78, and 86% in groups 1, 2, and 3, respectively. During follow-up, 17 (52%) patients lost donor-specific antibodies completely, and 10 (30%) lost some of donor-specific antibodies and/or decreased the strength of existing donor-specific antibodies.

Conclusions: These results indicated that in patients with strong donor-specific antibodies, the addition of plasmapheresis to high-dosage intravenous Ig decreases the incidence of acute rejection. The majority of the patients, whether they received intravenous Ig alone or with plasmapheresis, lost their donor-specific antibodies during follow-up.