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

Abstract

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.

Acute Hemolysis After High-Dose Intravenous Immunoglobulin Therapy in Highly HLA Sensitized Patients

“…IVIG is crucial to the successful transplantation of highly sensitized renal transplant candidates. It has been used alone or in conjunction with plasmapheresis for desensitization (9,18,19). More recently, IVIG together with rituximab was able to achieve an 80% transplant rate in a population that would otherwise be unlikely to receive a transplant (17).…”

Transplanting Against Histocompatibility Barriers

“…Akalin and colleagues found in their treatment protocols that AMR was observed only in patients with strong DSAs (MFI >6000 on Luminex® platform) [51]. Similarly Mayo clinic also found that the development of AMR was more likely in patients with strong DSAs and higher MCS on flow cytometry crossmatch [52].…”

“…The lowest rejection rates from Table 3 are seen in the data published by Mount Sinai using the addition of PP to IVIG/ATG pre-transplant conditioning protocols based on the intensity of DSA [51]. They studied a group of patients with CDC T cell negative crossmatch but T and/or B cell positive flow crossmatch.…”

Therapeutic plasma exchange for the treatment of pediatric renal diseases in 2013

“…Pre-transplant plasma exchange has been used in patients who are highly HLA sensitized to reduce donorspecific antibody levels and allow for successful renal transplantation, either from the deceased donor pool (by lowering PRA) or from a potential living donor (by eliminating a positive cross-match). In several studies of adult patients with high PRA, protocols including TPE (with low-dose intravenous immunoglobulin (IVIG) ± anti-CD20 therapy) have been shown to be superior to treatment with IVIG alone for desensitization with the goals of lowering donor specific antibodies (DSA) levels, reducing PRA, achieving a negative cross-match, avoiding post-operative AMR and prolonging graft survival [6][7][8]. A recent series of adult patients with end-stage renal disease (ESRD) demonstrated that patients who underwent desensitization with TPE and IVIG followed by living donor kidney transplantation had significantly improved survival than those who remained on dialysis and waited for an HLA-compatible deceased donor [9].…”