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.