The effectiveness of the combination of rituximab and high‐dose immunoglobulin in the immunomodulation of sensitized kidney transplant candidates

Abstract

Kidney transplantation faces many challenges not the least of which is the presence of pre-formed HLA antibodies. At our institution, we have used a combination of methods to immunomodulate sensitized patients. Most recently, this has been attempted with a combination of immunoglobulin (IVIG) and rituximab (Rituxan; Genetech, CA, USA). A total of 31 patients were followed for up to one yr following treatment with IVIG (2 gm/kg on day 1 and day 30) and rituximab (1 g - day 15). Antibody levels were followed serially at designated time points via solid-phase single-antigen beads (SAB) method (One Lambda, Inc., Canoga Park, CA, USA). Concentration of antibodies was based on median fluorescence intensity (MFI). The majority of patients had both class I and class II antibodies (79%). Our results showed that this protocol appeared to be patient and antibody specific. The most pronounced MFI reduction in antibodies occurred within the 30- to 100-d period post-treatment. Calculated panel-reactive antibodies decreased but rebound tended to occur by 104 d after antibody MFI nadir. Because of this rebound, it can be inferred that the patients did not show a durable increase in their potential for transplantation. The search for a more effective method to immunomodulate patients continues.

Effect of Treatment With Tabalumab, a B Cell–Activating Factor Inhibitor, on Highly Sensitized Patients With End-Stage Renal Disease Awaiting Transplantation

“…With the advent of solid‐phase antibody identification and the ability to quantitate the degree of antibody development, the transplant community has attempted to find a way to durably remove HLA antibodies with the goal of making the patient safer to transplant. That endeavor has thus far resulted in limited success . As noted, interventions to minimize sensitization have ranged from plasmapheresis and IVIG to pharmacological interventions including terminal complement and proteasome inhibition with multiple combinations thereof.…”

“…These approaches have shown promise but are limited in the clinical situations in which they can be used. However, the short period of antibody reduction and high frequency of antibody rebound poses a real challenge , suggesting that exploration of additional approaches is warranted.…”