Plasmapheresis in HLA-Immunosensitized Patients Prior to Kidney Transplantation

Abstract

Immunosensitization against the human lymphocyte antigen (HLA) is a problem in most transplant centers. It prolongs the waiting list time in addition to risk of frequent acute rejections. To avoid these problems, various pretransplantation approaches have been attempted e.g. plasmapheresis (PP). The present retrospective study reports our experience with PP in this respect over a 5 year period. Twenty-three chronic hemodialysis patients with circulating panel reactive antibodies (> or = 50%) and previous kidney graft rejections were treated with 12 PP each. In addition to this, immunosuppression with cyclophosphamide and prednisolone were administered on the first day of PP and after tapering continued until transplantation. HLA-antibodies, as measured by the panel reactive antibodies and the antibody titer, decreased from about 70% to 30% (p < 0.001) and 5 steps of titerdilution, respectively with PP and immunosuppressive drugs; Twenty-two patients were transplanted with cadaveric grafts. Eight grafts were lost due to irreversible rejection, and one due to the patient's death 2 months after transplantation. The cumulative five-year graft survival at the time of follow-up was 59%. Adequate kidney function (serum creatinine mean 150 mumol/l) was observed in all grafts (n = 3) still functioning 60 months posttransplant. We conclude that pretransplantation plasmapheresis together with immunosuppressive drugs (cyclophosphamide and prednisolone) is useful in the removal of HLA antibodies in immunized patients awaiting kidney transplantation. It can be considered a valuable approach to increase the chances of successful transplantations.

Diagnosis and treatment of antibody-mediated kidney allograft rejection

“…PP or IA is putatively an effective anti-humoral strategy. Apheresis was used as pre-emptive strategy in presensitized, in some studies even crossmatch-positive recipients, in order to prevent humoral rejection [84,85,86,87,88,89,90,911. On the other hand, apheresis was used as a strategy to reverse established episodes of AMR.…”

The Evaluation of the Renal Transplant Candidates: Clinical Practice Guidelines

“…Newer assays, utilizing more sensitive methods, e.g. enzyme-linked immunosorbent assay (ELISA) and Flow Bead, and using specific HLA antigens as targets have been introduced to identify antibodies specific to HLA antigens (1094)(1095)(1096)(1097)(1098)(1099). Knowing whether there are antibodies specific to HLA antigens helps in correctly interpreting the crossmatch results.…”

“…Recently, newer assays have been introduced that use more sensitive methods (ELISA and Flow Bead), and use specific soluble HLA target antigens immobilized in tray wells or on microbeads, to identify sera with IgG antibodies to HLA antigens (1094)(1095)(1096)(1097)(1098)(1099). Results from the ELISA-PRA have been shown to be more predictive of a posttransplant acute rejection and graft loss than the membrane dependent AHG-PRA assay (1094)(1095)(1096)(1097)(1098).…”

“…Results from the ELISA-PRA have been shown to be more predictive of a posttransplant acute rejection and graft loss than the membrane dependent AHG-PRA assay (1094)(1095)(1096)(1097)(1098). The Flow Bead PRA (Flow PRA) procedure can detect IgG antibody to HLA antigens in sera that are reported to be non-reactive (0% PRA) by ELISA (1093).…”

“…Over the past decade, several clinical trials of procedures designed to reduce titers of alloantibodies, e.g. plasmapheresis, immunoadsorption, intravenous immunoglobulin and intensified immunosuppression, have yielded promising, albeit preliminary results (1096,(1106)(1107)(1108)(1109)(1110)(1111).…”