Donor‐specific anti‐HLA antibodies in pediatric renal transplant recipients with creeping creatinine: Prevalence, histological correlations, and impact on patient and graft survival

Abstract

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.

Impacts of donor‐specific anti‐HLA antibodies and antibody‐mediated rejection on outcomes after intestinal transplantation in children

“…However, the diagnosis of AMR in SBTx is difficult to define in pediatric Tx. Children appear to be at high risk for developing DSA post‐solid organ Tx with higher DSA titers, compared with adults receiving Tx, and children might also require retransplantation. Studies have been lacking with detailed information about the clinical and pathological characteristics and treatment of this AMR.…”

Seeking Standardized Definitions for HLA-incompatible Kidney Transplants: A Systematic Review

“…A total of 6656 records underwent title and abstract screening. The full-text review was undertaken for 886 eligible articles; of these 78 articles discussed HLA incompatibility at the level of the antigen mismatch only, 64-141 whereas 163 articles assessed incompatibility by molecular genotyping, molecular mismatch analysis, and/or pretransplant DSA verification by solid-phase and/or by cell-based assays. 3,142-303 The Preferred Reporting Items for Systematic reviews and Meta-Analyses diagram outlining the article selection process is provided in Figure 1.…”

Urinary proteomics to diagnose chronic active antibody-mediated rejection in pediatric kidney transplantation - a pilot study

“…) for the detection of CKD , which was recommended by the FDA in 2016 for use in clinical trials of adults with diabetes mellitus . The similarity of both peptide patterns is not surprising since both diabetes mellitus and cABMR lead to a progression of fibrosis in the kidney and hence to progression of CKD . However, other marker peptides are unique for cABMR: Annexin A1 has an important role in the epithelial cells defense against renal ischemia–reperfusion (I/R) injury .…”