title: 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.
authors.affiliation: Department of Nephrology, Hospital JP. Garrahan, Buenos Aires, Argentina.
authors.forename: Marta Lidia
authors.initials: ML
authors.lastname: Monteverde
authors.affiliation: Department of Nephrology, Hospital JP. Garrahan, Buenos Aires, Argentina.
authors.forename: Alicia
authors.initials: A
authors.lastname: Chaparro
authors.affiliation: Department of Pathology, Hospital JP. Garrahan, Buenos Aires, Argentina.
authors.forename: Julio
authors.initials: J
authors.lastname: Goldberg
authors.affiliation: Department of Hemotherapy and Histocompatibility, Hospital JP. Garrahan, Buenos Aires, Argentina.
authors.forename: Cintia Yanina
authors.initials: CY
authors.lastname: Marcos
authors.affiliation: Department of Histocompatibility, Fundación Favaloro, Buenos Aires, Argentina.
authors.forename: Karim
authors.initials: K
authors.lastname: Padros
authors.affiliation: Department of Pathology, Hospital JP. Garrahan, Buenos Aires, Argentina.
authors.forename: Ziomara
authors.initials: Z
authors.lastname: Balbarrey
authors.affiliation: Department of Nephrology, Hospital JP. Garrahan, Buenos Aires, Argentina.
authors.forename: Liliana
authors.initials: L
authors.lastname: Briones
authors.affiliation: Department of Internal Medicine, Nephrology, University of Manitoba, Manitoba, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Rush
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006801:Humans; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation; D008297:Male; D016016:Proportional Hazards Models
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D007518:Isoantibodies; D003404:Creatinine
keywords: graft rejection; graft survival; kidney transplantation; patient non-adherence