3 years ago

Molecular phenotype of kidney transplant indication biopsies with inflammation in scarred areas

Philip F Halloran, Arthur Matas, Bertram L. Kasiske, Katelynn Madill-Thomsen, Martina Mackova, Konrad S Famulski

Abstract

In kidney transplant biopsies, inflammation in areas of atrophy‐fibrosis (i‐IFTA) is associated with increased risk of failure, presumably because inflammation is evoked by recent parenchymal injury from rejection or other insults, but some cases also have rejection. The present study explored the frequency of rejection in i‐IFTA, by histology Banff 2015 and microarray‐based molecular diagnostic system (MMDx). In unselected indication biopsies (108 i‐IFTA, 73 uninflamed IFTA (i0‐IFTA), and 53 no IFTA), i‐IFTA biopsies were later, more scarred, and had more antibody‐mediated rejection (ABMR) by histology (28%) and MMDx (45%). T cell‐mediated rejection (TCMR) was infrequent in i‐IFTA by histology (8%) and MMDx (16%). Twelve i‐IFTA biopsies (11%) had molecular TCMR not diagnosed by histology, although six were called Borderline and almost all had histologic TCMR lesions. The prominent feature of i‐IFTA biopsies was molecular injury e.g. AKI transcripts. In multivariate analysis of biopsies>1 year post‐transplant, the strongest associations with graft loss were AKI transcripts and histologic atrophy‐scarring; i‐IFTA was not significant when molecular AKI was included. We conclude that i‐IFTA in indication biopsies reflects recent/ongoing parenchymal injury, often with concomitant ABMR but few with TCMR. Thus application of Banff i‐IFTA in the population of late biopsies needs to be reconsidered.

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