Early immunosuppression treatment correlates with later de novo donor-specific antibody development after kidney and pancreas transplantation

Clin Transplant. 2015 Dec;29(12):1119-27. doi: 10.1111/ctr.12636. Epub 2015 Oct 16.

Abstract

Background: De novo donor-specific antibodies (dnDSA) post-transplant correlate with a higher risk of immunologic graft injury and loss following kidney and pancreas transplantation. Post-transplant dnDSA can occur within the first post-transplant year.

Methods: In this study, 817 of 1290 kidney and simultaneous kidney/pancreas recipients were tested for dnDSA post-transplant. Recipient immunosuppressive treatment at one, three, six, and 12 months post-transplant was correlated with dnDSA incidence by univariate and multivariate analyses.

Results: The overall incidence of dnDSA was 21.3% detected a median of 3.5 yr post-transplant. By univariate analysis, the immunosuppressive treatment at all time points correlated with dnDSA (p < 0.01). Month 6 treatment correlated best in multivariable analysis (p = 0.004). At six months, recipients receiving rapamune/mycophenolic acid (Rapa/MPA) had the highest dnDSA incidence at five yr (25.3%) and last follow-up (30.7%), those treated with cyclosporine/rapamune (CNI/Rapa) had the lowest incidence at five yr (10.8%) and last follow-up (18.6%), and cyclosporine/mycophenolic acid (CNI/MPA) treatment had an intermediate incidence at five yr (16.7%) and last follow-up (20.4%) (p < 0.01). Six-month CNI/MPA and Rapa/MPA treatment significantly correlated with dnDSA (hazard ratios of 2.36 and 1.80, respectively) by Cox proportional hazards regression modeling.

Conclusion: The risk of post-transplant dnDSA development correlates with early immunosuppressive management.

Keywords: donor-specific antibody; graft outcomes; immunosuppression; kidney transplant; survival.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Graft Rejection / blood
  • Graft Rejection / diagnosis
  • Graft Rejection / immunology*
  • Graft Survival / immunology*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Isoantibodies / blood
  • Isoantibodies / immunology*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Pancreas Transplantation / adverse effects*
  • Postoperative Complications
  • Prognosis
  • Risk Factors
  • Tissue Donors
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Isoantibodies