Factors at de novo donor-specific antibody initial detection associated with allograft loss: a multicenter study

Transpl Int. 2019 May;32(5):502-515. doi: 10.1111/tri.13395. Epub 2019 Feb 8.

Abstract

We aimed to evaluate patient factors including nonadherence and viral infection and de novo donor-specific antibody (dnDSA) characteristics [total immunoglobulin G (IgG), C1q, IgG3, and IgG4] as predictors of renal allograft failure in a multicenter cohort with dnDSA. We performed a retrospective observational study of 113 kidney transplant recipients with dnDSA and stored sera for analysis. Predictors of death-censored allograft loss were assessed by Cox proportional modeling. Death-censored allograft survival was 77.0% (87/113) during a median follow-up of 2.2 (IQR 1.2-3.7) years after dnDSA detection. Predictors of allograft failure included medication nonadherence [HR 6.5 (95% CI 2.6-15.9)], prior viral infection requiring immunosuppression reduction [HR 5.3 (95% CI 2.1-13.5)], IgG3 positivity [HR 3.8 (95% CI 1.5, 9.3)], and time post-transplant (years) until donor-specific antibody (DSA) detection [HR 1.2 (95% CI 1.0, 1.3)]. In the 67 patients who were biopsied at dnDSA detection, chronic antibody-mediated rejection [HR 11.4 (95% CI 2.3, 56.0)] and mixed rejection [HR 7.4 (95% CI 2.2, 24.8)] were associated with allograft failure. We conclude that patient factors, including a history of viral infection requiring immunosuppression reduction or medication nonadherence, combined with DSA and histologic parameters must be considered to understand the risk of allograft failure in patients with dnDSA.

Keywords: HLA-antibody post-transplantation; histocompatibility and immunogenetics; infection; kidney clinical; other; rejection.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Allografts
  • Antibodies / immunology*
  • Biopsy
  • Female
  • Glomerulonephritis / surgery
  • Graft Rejection / immunology
  • Graft Survival
  • HLA Antigens / immunology
  • Humans
  • Immunoglobulin G / immunology
  • Immunosuppressive Agents
  • Kidney Failure, Chronic / immunology*
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation*
  • Male
  • Medication Adherence
  • Middle Aged
  • Postoperative Period
  • Retrospective Studies
  • Risk Factors
  • Tissue Donors
  • Transplant Recipients
  • Transplantation, Homologous

Substances

  • Antibodies
  • HLA Antigens
  • Immunoglobulin G
  • Immunosuppressive Agents