No Inhibitory Effect of Pre-Transplant Desensitization Treatment with Rituximab or Splenectomy on de Novo HLA Antibody Production in Renal Transplantation: 2338

Introduction: De novo HLA antibody (Ab) production has been reported to be associated with chronic antibody mediated rejection (CAMR) in renal transplantation (RTx), resulting in poor graft outcome. B cell-targeted therapy has been suggested as a potential strategy. The effect of immunosuppressive treatment including pre-transplant splenectomy (SPX) or rituximab (RIT) on de novo HLA Ab production was examined. Methods: 337 living donor renal transplants were performed between 2005 and 2009. As pre-transplant DSA-positive recipients (n=17) were excluded, 320 transplants including 228 ABO-identical/compatible RTx (ABO-Id/C) and 92 ABO-incompatible RTx (ABO-In) were analyzed. Immunosuppressive regimen consisted of basiliximab, calcineurin inhibitor (CSA or TAC), antimetablite (MMF or mizoribine: MZR) and steroid. The dose was adjusted according to pharmacokinetics (AUC0-4 or 0-12). Recipients in ABO-In were additionally pre-treated with antimetablite (cyclophosphamide or MMF for 2W), plasmapheresis and splenectomy (SPX) or rituximab (RIT; from 2008) or none (because of low anti-A/B Ab titer). In 2010 and 2011, DSA was examined in 293 recipients using LABScreen single antigen beads (MFI>1000), after HLA Ab screening using FlowPRA or LABScreen Mixed. Results: Death-uncensored 5-year graft survivals were 98.1% in ABO-Id/C and 90.9% in ABO-In (Table). During the study period, only 2 developed CAMR. De novo HLA Ab including DSA (n=24) and NDSA (N=15) were detected in 39 (13.3%) recipients. Most of DSA were directed to class II (22/24), while a majority of NDSA were directed to class I (10/15). Rates of de novo HLA Ab were 13.9% in ABO-Id/C and 11.7% in ABO-In (14.3% in RIT-treated and 13.2% in post-SPX recipients). De novo HLA Abs were produced in 13.8% of CSA-, 12.0% of TAC-, 13.0% of MMF- and 19.0% of MZR-treated recipients. However, renal function remained stable even in recipients with de novo HLA Ab (eGFR: 47.2±16.3).Table: [Graft survival, de novo HLA antibody and eGFR]Conclusion: We obtained the excellent graft outcome in living donor RTx, whereas graft survival of ABO-In was somewhat lower than that of ABO-Id/C. The incidence of CAMR was very low within 5 years, although de novo HLA Ab was observed in SPX or RIT-pretreated recipients (ABO-In) as well as untreated recipients (ABO-Id/C). Neither pre-transplant SPX nor RIT treatment seemed to have an inhibitory effect on de novo HLA antibody production. Chronic AMR could be mainly controlled by optimizing immunosuppressive therapy based on pharmacokinetics and therapeutic drug monitoring. Careful, long-term follow-up would be essential.