C1q binding is not an independent risk factor for kidney allograft loss after an acute antibody-mediated rejection episode: a retrospective cohort study

Transpl Int. 2017 Mar;30(3):277-287. doi: 10.1111/tri.12905.

Abstract

After kidney transplantation, C4d is an incomplete marker of acute antibody-mediated rejection (AMR) and C1q-binding donor-specific antibodies (DSA) have been associated with allograft survival. However, the impact on allograft survival of C1q+ DSA after clinical AMR has not been studied yet. We analysed retrospectively in clinical AMR C4d staining and C1q-binding impact on allograft survival. We compared clinical, histological and serological features of C4d- and C4d+ AMR, C1q+ and C1q- DSA AMR and analysed C4d and C1q-binding impact on allograft survival. Among 500 for-cause kidney allograft biopsies, 48 fulfilled AMR criteria. C4d+ AMR [N = 18 (37.5%)] have significantly higher number class I DSA (P = 0.02), higher microvascular score (P = 0.02) and more transplant glomerulopathy (P = 0.04). C1q+ AMR [N = 20 (44%)] presented with significantly more class I and class II DSA (P = 0.005 and 0.04) and C4d+ staining (P = 0.01). Graft losses were significantly higher in the C4d+ group (P = 0.04) but similar in C1q groups. C4d+ but not C1q+ binding was an independent risk factor for graft loss [HR = 2.65; (1.11-6.34); P = 0.028]. In our cohort of clinical AMR, C4d+ staining but not C1q+ binding is an independent risk factor for graft loss. Allograft loss and patient survival were similar in C1q+ and C1q- AMR.

Keywords: C1q-binding DSA; C4d staining; allograft survival; antibody-mediated rejection; kidney transplantation.

MeSH terms

  • Adult
  • Cohort Studies
  • Complement C1q / metabolism*
  • Complement C4b / metabolism
  • Female
  • Graft Rejection / etiology*
  • Graft Rejection / immunology*
  • Humans
  • Isoantibodies / metabolism*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Peptide Fragments / metabolism
  • Retrospective Studies
  • Risk Factors
  • Tissue Donors

Substances

  • Isoantibodies
  • Peptide Fragments
  • Complement C1q
  • Complement C4b
  • complement C4d