Donor-specific anti-HLA antibodies (DSA) causing CAMR are responsible for a high proportion of long-term graft failures after RTX. We studied the prevalence of DSA in RTX children biopsied for creeping Cr, its relationship with NA, and patient and graft survival according to histopathology. Between 2008 and 2013, 92 children were biopsied at a median of 38 months post-RTX. At biopsy, the prevalence of DSA was 49% and C4d 70%. NA rate was 45%, higher in adolescents (60%). Most frequent diagnoses were CAMR (72%) and interstitial fibrosis with tubular atrophy (IFTA) (28%). Forty-five of 66 patients with CAMR (68%) had detectable DSA. Twenty-one DSA-negative patients with CAMR had histological damage (IFTA + C4d positivity). C4d was detected in 64 of 66 biopsies with CAMR. Recipients with IFTA alone had neither C4d, nor detectable DSA, and were adherent. Graft survival at five yr was 89% in patients with CAMR, 79% in those with CAMR + TCMR Banff I, 33% in those with CAMR + TCMR Banff II, and 96% in those with IFTA. ABMR and complement activation were frequent in children biopsied for creeping Cr. Recipients with DSA were more likely to be non-adherent and have CAMR or CAMR + TCMR and worse graft survival.