C4d staining in post-reperfusion renal biopsy is not useful for the early detection of antibody-mediated rejection when CDC crossmatching is negative

Nephrol Dial Transplant. 2011 Apr;26(4):1388-92. doi: 10.1093/ndt/gfq549. Epub 2010 Sep 15.

Abstract

Background: Sensitized patients (pts) may develop acute antibody-mediated rejection (AMR) due to preformed donor-specific antibodies, undetected by pre-transplant complement-dependent cytotoxicity (CDC) crossmatch (XM). We hypothesized that C4d staining in 1-h post-reperfusion biopsies (1-h Bx) could detect early complement activation in the renal allograft due to preformed donor-specific antibodies.

Methods: To test this hypothesis, renal transplants (n = 229) performed between June 2005 and December 2007 were entered into a prospective study of 1-h Bx and stained for C4d by immunofluorescence. Transplants were performed against a negative T-cell CDC-XM with the exception of three cases with a positive B-cell XM.

Results: All 229 1-h Bx stained negative for C4d. Fourteen pts (6%) developed AMR. None of the 14 protocol 1-h Bx stained positive for C4d in peritubular capillaries (PTC). However, all indication biopsies-that diagnosed AMR-performed at a median of 8 days after transplantation stained for C4d in PTC.

Conclusions: These data show that C4d staining in 1-h Bx is, in general, not useful for the early detection of AMR when CDC-XM is negative.

MeSH terms

  • Adolescent
  • Adult
  • Biopsy
  • Complement C4b / immunology*
  • Complement C4b / metabolism
  • Cytotoxicity, Immunologic*
  • Female
  • Graft Rejection / etiology
  • Graft Rejection / immunology*
  • Histocompatibility Testing*
  • Humans
  • Isoantibodies / immunology*
  • Kidney / pathology
  • Kidney / surgery
  • Kidney Diseases / complications
  • Kidney Diseases / therapy
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism
  • Prospective Studies
  • Reperfusion

Substances

  • Isoantibodies
  • Peptide Fragments
  • Complement C4b
  • complement C4d