title: Early subclinical inflammation correlates with outcomes in positive crossmatch kidney allografts.
abstract: The aim of this study was to investigate correlations between early subclinical findings (10- and 90-day histology and gene expression data) and late outcomes (transplant glomerulopathy and graft loss) in positive crossmatch kidney transplants (+XMKTx). We compared 34 +XMKTx (19 receiving eculizumab and 15 receiving standard of care without eculizumab) to 13 -XMKTx (between August 2001 and August 2011). At 10 days, light microscopy identified subclinical inflammation in only 18% of +XMKTx, while intragraft gene expression identified inflammation in 79% (gene sets for activated macrophages, dendritic cells, NK cells or T cells). Inflammation persisted at 90 days and was associated with the development of transplant glomerulopathy by 2 years and graft loss. In contrast, endothelial cell (EC) changes present at 90 days by either electron microscopy or gene expression were not associated with transplant glomerulopathy or graft loss in this cohort. Eculizumab treatment did not appear to alter inflammation or EC changes. Therefore, intragraft inflammation might be an appropriate surrogate marker of progression and also a target of therapy to prevent chronic antibody-mediated rejection.
authors.affiliation: Division of Transplantation Surgery, Department of Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Dean
authors.affiliation: Division of Transplantation Surgery, Department of Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Walter D
authors.initials: WD
authors.lastname: Park
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Lynn D
authors.initials: LD
authors.lastname: Cornell
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Schinstock
authors.affiliation: Division of Transplantation Surgery, Department of Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Stegall
mesh_terms: D000328:Adult; D064591:Allografts; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001706:Biopsy; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000150:complications / Q000175:diagnosis* / Q000517:prevention & control; D006085:Graft Survival; D006650:Histocompatibility Testing; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000209:etiology*; D007668:Kidney / Q000648:ultrastructure; D016030:Kidney Transplantation; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C481642:eculizumab
keywords: antibody; gene expression; inflammation; kidney transplant; rejection