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Clin Transplant. 2016 Aug;30(8):925-33. doi: 10.1111/ctr.12766. Epub 2016 Jun 22.

Early subclinical inflammation correlates with outcomes in positive crossmatch kidney allografts.

Author information

1
Division of Transplantation Surgery, Department of Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA.
2
Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA.
3
Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.

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.

KEYWORDS:

antibody; gene expression; inflammation; kidney transplant; rejection

PMID:
27225518
DOI:
10.1111/ctr.12766
[Indexed for MEDLINE]

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