**ii.** C4d negative AMR

AMR in the absence of PTC C4d staining has been reported more frequently. In an analysis of 173 indication kidney biopsies, *Sis et al* demonstrated that a combination of high expression of endothelial-associated transcripts (ENDAT) detected using microarray on tissue biopsy, suggesting endothelial damage from alloantibody, plus the presence of DSA was strongly associated with morphological evidence of AMR but only 38% of these biopsies had evidence of PTC C4d positivity [46]. Other studies have corroborated this initial finding suggesting that over reliance of C4d positivity to diagnose acute or chronic AMR could miss up to 60% of patients with morphological evidence of AMR and C4d staining should always be interpreted in the context of tissue morphology [47, 48]
