Significance of C4d Banff Scores in Early Protocol Biopsies of Kidney Transplant Recipients with Preformed Donor‐Specific Antibodies (DSA)

The significance of C4d‐Banff scores in protocol biopsies of kidney transplant recipients with preformed donor‐specific antibodies (DSA) has not been determined. We reviewed 157 protocol biopsies from 80 DSA+ patients obtained at 3 months and 1 year post‐transplant. The C4d Banff scores (1,2,3) were associated with significant increments of microcirculation inflammation (MI) at both 3 months and 1 year post‐transplant, worse transplant glomerulopathy and higher class II DSA‐MFI (p < 0.01). Minimal‐C4d had injury intermediate between negative and focal, while focal and diffuse‐C4d had the same degree of microvascular injury. A total of 54% of patients had variation of C4d score between 3 months and 1 year post‐transplant. Cumulative (3 month + 1 year) C4d scores correlated with long‐term renal function worsening (p = 0.006). However, C4d staining was not a sensitive indicator of parenchymal disease, 55% of C4d‐negative biopsies having evidence of concomitant MI. Multivariate analysis demonstrated that the presence of MI and class II DSA at 3 months were associated with a fourfold increased risk of progression to chronic antibody‐mediated rejection independently of C4d (p < 0.05). In conclusion, the substantial fluctuation of C4d status in the first year post‐transplant reflects a dynamic humoral process. However, C4d may not be a sufficiently sensitive indicator of activity, MI and DSA being more robust predictors of bad outcome.