Allosensitization after transplant failure: the role of graft nephrectomy and immunosuppression - a retrospective study

Transpl Int. 2019 Sep;32(9):949-959. doi: 10.1111/tri.13442. Epub 2019 Apr 26.

Abstract

There are conflicting data about the role of transplant nephrectomy and immunosuppression withdrawal on the development of allosensitization and the impact on re-transplantation. We divided 109 first graft recipients into two groups according to whether they underwent nephrectomy (NX+, n = 61) or their graft was left in situ (NX-, n = 48). Sera were assessed for HLA-A/B/Cw/DR/DQ antibodies at the time of NX/transplant failure and after 3, 6, 12, 24 months. The NX+ group showed a higher rate of donor specific antibody (DSA) and non-DSA human leukocyte antigen (HLA) antibody production at all the time points. Multivariable analysis showed that nephrectomy was a strong, independent risk factor for the development of DSAs after 12 and 24 months (P = 0.005 and 0.008). In the NX- group, low tacrolimus levels correlated with DSA formation (AUC 0.817, P = 0.002; best cut-off level 2.9 ng/ml). Analysis with a standardized pool of UK donors showed a more difficult grade of HLA matchability following nephrectomy compared with the NX- group. Nephrectomy is followed by the long-term production of DSA and non-DSA HLA antibodies and negatively impacts on the chances of finding a HLA-compatible kidney. Tacrolimus levels ≥3 ng/ml are protective against the development of allosensitization and could facilitate re-transplantation in the NX- group.

Keywords: allosensitization; donor-specific antibody; tacrolimus; transplant nephrectomy.

MeSH terms

  • Adult
  • Aged
  • Female
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Immunosuppression Therapy*
  • Immunosuppressive Agents / administration & dosage
  • Kidney Failure, Chronic / immunology*
  • Kidney Failure, Chronic / surgery
  • Male
  • Middle Aged
  • Nephrectomy / adverse effects*
  • Postoperative Complications / immunology*
  • Postoperative Complications / surgery
  • Retrospective Studies
  • Tacrolimus / administration & dosage
  • Transplantation Immunology*

Substances

  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Immunosuppressive Agents
  • Tacrolimus