*Purpose: C4d deposition in the peritubular capillaries (PTCs) is associated with acute antibody mediated rejection (AMR) and reduced renal allograft survival. PTC C4d positivity, however, can be observed in the presence or absence of either microvascular inflammation (MVI, defined as peritubular capillaritis and/or glomerular capillaritis) or donor specific antibody (DSA). The purpose of this study was to examine the effects of PTC C4d staining in renal allograft biopsies, and to evaluate the effects of concomitant MVI and/or DSA on renal allograft survival.

*Methods: Sunquest Power Path software was used to identify renal transplant patients from 2007 to 2017 with C4d positive biopsies. A retrospective chart review was performed on patients who underwent for cause renal allograft biopsy. Inclusion criteria for analysis was PTC C4d positivity and exclusion criteria included mixed acute rejection. One-Hundred and nineteen patients met inclusion criteria. The primary endpoints included graft outcome, DSA presence, DSA absence, C4D grade and AMR therapy. Demographic and immunological data collected: see table 1. Subgroups for analysis included: MVI only, DSA only, MVI and DSA, no MVI or DSA.

*Results: Figure 1 displays the mean number of patients per characteristic and outcome measured. The Death Censored Graft Survival (DCGF) was highest in the MVI only group (P value 0.031). Graft failure was worse at five years post biopsy in the DSA only group of C4d positive biopsies based on overall graft survival. The largest subgroup was patients with isolated C4d in the absence of MVI or DSA, of which 90% did not receive AMR treatment and 58% had Banff score consistent with chronic rejection, and had a better DCGF than the DSA only group and the MVI and DSA group. The DCGF is depicted in Figure 2.

*Conclusions: DSA presence in addition to C4d positivity leads to inferior overall survival. MVI did not strongly correlate with graft failure as the MVI only group had significantly better death censored graft survival compared to any other group. Isolated C4d positivity on for cause biopsies may be sufficient to warrant AMR therapy, regardless of DSA or MVI status.

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