Transplant glomerulopathy may occur in the absence of donor-specific antibody and C4d staining

Clin J Am Soc Nephrol. 2007 Nov;2(6):1261-7. doi: 10.2215/CJN.02420607. Epub 2007 Oct 17.

Abstract

Background and objectives: Transplant glomerulopathy (TGP) has been proposed to be a component of chronic antibody-mediated rejection (AMR). We have studied 36 patients with TGP and 51 patients with chronic allograft nephropathy (CAN) but without TGP for C4d staining and donor-specific anti-HLA antibodies (DSA) to investigate the alloantibody-mediated mechanisms.

Design, setting, participants, & measurements: Allograft biopsies were stained with C4d staining and DSAs were studied by Luminex Flow Beads. Allograft biopsies were done at a mean of 5.3 +/- 5.0 and 5.6 +/- 4.6 yr after transplantation in patients with CAN and TGP, respectively.

Results: The mean creatinine level at the time of the biopsy was 2.7 +/- 1.2 mg/dl in each group. Proteinuria of >1.0 g/d was more common in patients with TGP (61 versus 25%; P = 0.002). Whereas three patients with TGP had a history of acute AMR, none of the patients with CAN had. Mean chronicity score of the biopsies were 1.7 +/- 0.7 in patients with CAN and 1.9 +/- 0.8 in patients with TGP. Biopsies from only two (4%) patients with CAN and four (11%) patients with TGP had diffuse C4d positivity. DSA were found in 36% of TGP and 33% of CAN patients.

Conclusions: These results suggest that a substantial number of patients with TGP did not have positive C4d staining or DSA, indicating that a non-alloantibody-mediated process may be involved in the development of TGP in some patients.

MeSH terms

  • Adult
  • Aged
  • Chronic Disease
  • Complement C4b / analysis*
  • Female
  • Graft Rejection / etiology*
  • Graft Rejection / immunology
  • Graft Rejection / pathology
  • HLA Antigens / immunology*
  • Humans
  • Isoantibodies / blood*
  • Kidney Glomerulus / pathology*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Peptide Fragments / analysis*
  • Staining and Labeling
  • Tissue Donors*
  • Transplantation, Homologous

Substances

  • HLA Antigens
  • Isoantibodies
  • Peptide Fragments
  • Complement C4b
  • complement C4d