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Clinical Trial
. 2010 Nov 27;90(10):1099-105.
doi: 10.1097/TP.0b013e3181f7fec9.

Optimal cutoff point for immunoperoxidase detection of C4d in the renal allograft: results from a multicenter study

Gretchen S Crary  1 , Yassaman Raissian, Robert C Gaston, Sita M Gourishankar, Robert E Leduc, Roslyn B Mannon, Arthur J Matas, Joseph P Grande
Affiliations
Clinical Trial

Optimal cutoff point for immunoperoxidase detection of C4d in the renal allograft: results from a multicenter study

Gretchen S Crary et al. Transplantation. .

Abstract

Background: Although C4d deposition in peritubular capillaries has been identified as a strong risk factor for subsequent renal allograft loss, the optimal cutoff for the fraction of peritubular capillaries needed to establish a positive stain in formalin-fixed, paraffin-embedded material has not been defined systematically. The objective of this study was to establish the threshold for positive staining that best predicts renal outcome in renal biopsies in a multicenter study in which local and central pathologic conditions were compared.

Methods: Unstained renal biopsy slides were obtained from 296 patients. The percentage of peritubular capillaries staining positively for C4d was detected by immunoperoxidase staining.

Results: The percentage C4d deposition ranged from 0% to 90% with 44% (129/296) having a positive percentage of C4d staining. The median for positive cases was 25%. Local C4d+ results were reported qualitatively, with 28% recorded as positive for C4d. Using a centrally determined cutoff of 10%, tests for agreement of local and central C4d staining were fair (κ 0.40, 95% confidence interval 0.29-0.51). Raising the centrally determined cutoff to 25% or 50% did not change the κ values (0.44 and 0.41, respectively). By Cox proportional hazards model, C4d positivity (centrally determined assessment) using a cutoff of 10% was the strongest predictor of time to graft loss (hazard ratio 2.66, 95% confidence interval 1.68-4.21). Centrally determined C4d positivity correlated with Banff scores indicative of acute inflammation but not with scores indicative of fibrosis/atrophy or transplant glomerulopathy.

Conclusions: Our findings indicate that C4d positivity, defined as more than or equal to 10% by immunoperoxidase, is a strong predictor of graft loss.

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Figures

Figure 1
Figure 1
Representative histopathologic section of renal biopsy stained by immunoperoxidase for C4d showing diffuse positive staining within peritubular capillaries (panel A). Representative section of a renal biopsy showing no significant staining for C4d (panel B).
Figure 2
Figure 2
Time to graft failure by C4d status. Immunoperoxidase staining for C4d was centrally performed and read in a blinded fashion. A) Time to graft failure as a function of C4d status, using a centrally-defined cut-off threshold of 10%. B) Time to graft failure as a function of C4d status, using centrally-defined cut-off values of <10% (negative), 10-24%, or ≥25%.
Figure 3
Figure 3
Time to graft failure in patients (n=296) whose biopsies show positive C4d staining (n=68), acute rejection (n=35), both (n=37), or neither (n=156).
See this image and copyright information in PMC

References

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