Abstract

Introduction: Donor-specific anti-HLA antibodies (DSA) and C4d deposits in peritubular capillaries are associated with humoral rejection and graft loss. Aim: To assess in children with a renal transplant (RTX) who underwent a biopsy due to creeping creatinine ≥ 30% during 3 to 12 months previously: 1. Prevalence of DSA and C4d. 2. Graft survival according to histopathological diagnosis (Banff). 3. Risk factors of graft loss and DSA post RTX. Patients and Methods Between December 1998 and March 2013 700 RTX were performed. The clinical charts of children who underwent a kidney biopsy were retrospectively assessed. Results: Ninety-two children, 53 boys, were included in the study. Mean age at RTX was 9.6±3 years; 68 received a deceased donor (DD) organ; 90 had a first RTX, with a biopsy at a mean of 38 months post RTX (IQR: 20-66). Follow-up was 6.3± 3 years. Baseline immunosuppression was steroids, MMF/MPS and CsA (n=74), TAC (n=10), and SRL (n=8); DD RTX recipients received thymoglobulin induction. DSA (Luminex) were detected in 48%, diffuse C4d (IFI) in 48% and focal C4d in 27%. DSA were found in 93% of C4d-positive vs. 7% of C4d-negative biopsies (p<0.001) Histopathology: Chronic rejection (CR): n=53 with Transplant Glomerylopathy n=7, IFTA n=31, ACR n=4, others n=4. Graft survival at 12 years: IFTA 96%, CR: 53% (p: 0.02). Risk factors for graft loss (multivariate analysis): Acute tubular necrosis: (HR 7.3, 95%CI: 1.7-31), Chronic rejection with ACR: (HR 4.6, 95%CI:1.6-12.5), and age at RTX (HR 1.2: 95%CI: 1.2-1.5). Risk factors for post RTX DSA: No-adherence(OR: 6.9, 95CI%: 2.3-20), and peritubular capillaritis (HR: 2.4 IC95%, 1.5-19.9). Conclusion: Antibody-mediated damage was common in children with graft failure. Significant association was found between microvascular inflammation, no-adherence and the presence of DSA. Vascular rejection and concomitant ACR, acute tubular necrosis, and age at RTX were predictors of graft loss.

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