ABO Blood Group Antibody Elimination by a Combination of Semiselective Immunoadsorption Therapy and Membrane Filtration

-Background and study aims

ABO-incompatible living donor kidney transplantation offers the possibility to expand the donor pool by approximately 30%. A variety of different desensitization protocols were shown to enable successful transplantation across major ABO barriers. In this context, apheresis for antibody depletion represents the therapeutic mainstay. Two distinct technical principles, plasmapheresis and ABO antigen-specific immunoadsorption, were shown to allow for excellent short- and intermediate-term outcomes. A particular technical advantage of immunoadsorption may be its high selectivity regarding antibody depletion, which precludes major losses of essential plasma constituents, including coagulation factors and albumin, even after treatment of large plasma volumes. Nevertheless, high treatment costs associated with the use of ABO-specific columns (that are not approved for reuse) may limit their widespread clinical application.

The efficiency of semi-selective immunoadsorption technologies regarding ABO antibody depletion and recipient desensitization is less well established. Theoretically, non-antigen-specific immunoglobulin depletion using protein A-, GAM peptide-, or anti-Ig antibody-based adsorbers, could bring about several advantages, such as lower treatment costs associated with the use of reusable twin columns, and the potential to simultaneously deplete antibodies also against HLA antigens. A critical drawback, however, may be an evident inefficiency regarding (ABO-specific) IgM depletion, and this could pose a considerable risk of rejection.

One strategy to overcome the drawback of incomplete IgM depletion could be the use of semiselective immunoadsorption combined with other antibody depletion technologies. In this context, one attractive option could be an enhancement of antibody elimination by connecting a membrane filter (cascade filter) to the immunoadsorption device. We propose to conduct an open randomized crossover study that is designed to see if membrane filtration when applied as an adjunct to semiselective immunoadsorption (GAM peptide adsorbers) is able to enhance anti-ABO IgM elimination to an extent comparable to ABO antigen-specific immunoadsorption. The results of this study, which will enrol 14 patients receiving IA treatment for clinical indications outside the transplantation field, are expected to provide a valuable basis for the use of combined apheresis approaches in the context of ABO-incompatible kidney transplantation.

-Who can participate?