Thrombotic microangiopathy and peritubular capillary C4d expression in renal allograft biopsies

Clin J Am Soc Nephrol. 2011 Feb;6(2):395-403. doi: 10.2215/CJN.05870710. Epub 2010 Oct 21.


Background and objectives: This study characterizes the pathologic and clinical relationships of thrombotic microangiopathy (TMA) to antibody-mediated rejection (AMR) in renal allograft biopsies.

Design, setting, participants, & measurements: Consecutive renal allograft biopsies, routinely stained for C4d over a period of 51 months (n=1101), were reviewed. For comparative analysis of histology and clinical features, additional patients with TMA and peritubular capillary (PTC) C4d (n=5) were combined with those identified in the 51-month period of review (n=6).

Results: One hundred eighty-two of 1073 adequate biopsies from 563 allografts had PTC C4d in the study period. Six of 37 biopsies with TMA had PTC C4d (five at ≤90 days and one at 213 days). Early (≤90 days) C4d+ biopsies (n=5) had more frequent TMA (11.9% C4d+ versus 3.4% C4d-; odds ratio, 3.84; P=0.03). Graft loss was significantly greater in an early C4d+TMA+ group (n=5 study+2 archival patients) than in C4d+ controls without TMA (n=21) (57% versus 9.5%; P=0.02). Early TMA+C4d+ biopsies had more severe glomerulopathy and less severe arteriolopathy than TMA+C4d- and had more frequent neutrophilic capillaritis than TMA-C4d+ biopsies.

Conclusions: TMA was infrequent in this series of unselected, consecutive, renal allograft biopsies (3.4%). PTC C4d may be a significant risk factor for early TMA, and TMA is associated with glomerular thrombi and neutrophilic capillaritis. TMA in allografts with suspected AMR may portend a higher risk of graft loss.

MeSH terms

  • Adult
  • Biopsy
  • Capillaries / immunology*
  • Capillaries / pathology
  • Case-Control Studies
  • Chi-Square Distribution
  • Chicago
  • Complement C4b / analysis*
  • Female
  • Graft Rejection / immunology*
  • Graft Rejection / pathology
  • Graft Survival*
  • Humans
  • Immunohistochemistry
  • Kidney Transplantation / immunology*
  • Male
  • Middle Aged
  • Odds Ratio
  • Peptide Fragments / analysis*
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Thrombotic Microangiopathies / immunology*
  • Thrombotic Microangiopathies / pathology
  • Time Factors
  • Transplantation, Homologous


  • Peptide Fragments
  • Complement C4b
  • complement C4d