Subclinical rejection-free diagnostic after kidney transplantation using blood gene expression

Kidney Int. 2023 Jun;103(6):1167-1179. doi: 10.1016/j.kint.2023.03.019. Epub 2023 Mar 27.


We previously established a six-gene-based blood score associated with operational tolerance in kidney transplantation which was decreased in patients developing anti-HLA donor-specific antibodies (DSA). Herein, we aimed to confirm that this score is associated with immunological events and risk of rejection. We measured this using quantitative PCR (qPCR) and NanoString methods from an independent multicenter cohort of 588 kidney transplant recipients with paired blood samples and biopsies at one year after transplantation validating its association with pre-existing and de novo DSA. From 441 patients with protocol biopsy, there was a significant decrease of the score of tolerance in 45 patients with biopsy-proven subclinical rejection (SCR), a major threat associated with pejorative allograft outcomes that prompted an SCR score refinement. This refinement used only two genes, AKR1C3 and TCL1A, and four clinical parameters (previous experience of rejection, previous transplantation, sex of recipient and tacrolimus uptake). This refined SCR score was able to identify patients unlikely to develop SCR with a C-statistic of 0.864 and a negative predictive value of 98.3%. The SCR score was validated in an external laboratory, with two methods (qPCR and NanoString), and on 447 patients from an independent and multicenter cohort. Moreover, this score allowed reclassifying patients with discrepancies between the DSA presence and the histological diagnosis of antibody mediated rejection unlike kidney function. Thus, our refined SCR score could improve detection of SCR for closer and noninvasive monitoring, allowing early treatment of SCR lesions notably for patients DSA-positive and during lowering of immunosuppressive treatment.

Trial registration: NCT02900040.

Keywords: antibody-mediated rejection; biomarker; donor-specific antibodies; gene expression; kidney transplantation; subclinical rejection.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies
  • Antilymphocyte Serum
  • Gene Expression
  • Graft Rejection / diagnosis
  • Graft Rejection / genetics
  • Graft Rejection / prevention & control
  • HLA Antigens / genetics
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Isoantibodies
  • Kidney Transplantation* / adverse effects
  • Retrospective Studies
  • Tacrolimus / therapeutic use


  • Immunosuppressive Agents
  • Antibodies
  • Tacrolimus
  • Antilymphocyte Serum
  • HLA Antigens
  • Isoantibodies

Associated data