Effect of Early Immunosuppression Therapy on De Novo Anti-Human-Leukocyte-Antigen Antibody After Kidney Transplantation

Transplant Proc. 2018 Oct;50(8):2382-2387. doi: 10.1016/j.transproceed.2018.03.043. Epub 2018 Mar 16.

Abstract

The aim of the study was to investigate the effect of immunosuppression therapy early after kidney transplantation, particularly exposure of mycophenolic acid (MPA) and calcineurin inhibitor (CNI), on posttransplantation de novo HLA antibody production.

Methods: A single-center retrospective cohort study was performed at the First Affiliated Hospital of Sun Yat-sen University, enrolling the kidney transplant or pancreas-kidney transplant recipients who had surgery between January 2010 and February 2016.

Results: A total of 214 recipients were included in the study with a median follow-up period of 1.06 years. A total of 30 recipients (14.0%) were positive in HLA antibody detection posttransplant with a median follow-up period of 1.46 years. Ten recipients (4.7%) lost their allograft function during follow-up, and 6 of them (60%) developed de novo HLA antibody after graft failure. Multivariate analysis showed that acute rejection significantly increased the risk of de novo HLA antibody (hazard ratio [HR], 2.732). Intensified MPA dosing therapy reduced the risk by 59.8% (HR, 0.402); low-dose CNI therapy increased the risk by 33.3% (HR, 1.333), and the effect of extremely low-dose CNI therapy was even larger (HR, 2.242).

Conclusion: The risk of de novo HLA antibody can be decreased by reducing the risk of acute rejection. A tendency was seen in low-dose CNI therapy to increase the risk of de novo HLA antibody, but intensified MPA dosing therapy may provide an umbrella protection effect by reducing the risk. Prospective study was required to confirm the effects.

MeSH terms

  • Adult
  • Autoantibodies / immunology*
  • Cohort Studies
  • Female
  • Graft Rejection / immunology
  • Graft Survival / drug effects
  • HLA Antigens / immunology*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation*
  • Male
  • Mycophenolic Acid / therapeutic use
  • Retrospective Studies
  • Transplantation, Homologous

Substances

  • Autoantibodies
  • HLA Antigens
  • Immunosuppressive Agents
  • Mycophenolic Acid