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The causes, significance and consequences of inflammatory fibrosis in kidney transplantation: The Banff i‐IFTA lesion
Author(s) -
Nankivell Brian J.,
Shingde Meena,
Keung Karen L.,
Fung Caroline LS.,
Borrows Richard J.,
O'Connell Philip J.,
Chapman Jeremy R.
Publication year - 2018
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14609
Subject(s) - medicine , immunosuppression , transplantation , fibrosis , kidney disease , kidney transplantation , pathology , gastroenterology , urology
Inflammation within areas of interstitial fibrosis and tubular atrophy (i‐ IFTA ) is associated with adverse outcomes in kidney transplantation. We evaluated i‐ IFTA in 429 indication‐ and 2052 protocol‐driven biopsy samples from a longitudinal cohort of 362 kidney–pancreas recipients to determine its prevalence, time course, and relationships with T cell–mediated rejection ( TCMR ), immunosuppression, and outcome. Sequential histology demonstrated that i‐ IFTA was preceded by cellular interstitial inflammation and followed by IF / TA . The prevalence and intensity of i‐ IFTA increased with developing chronic fibrosis and correlated with inflammation, tubulitis, and immunosuppression era ( P < .001). Tacrolimus era–based immunosuppression was associated with reduced histologic inflammation in unscarred and scarred i‐ IFTA compartments, ameliorated progression of IF , and increased conversion to inactive IF / TA (compared with cyclosporine era, P < .001). Prior acute (including borderline) TCMR and subclinical TCMR were followed by greater 1‐year i‐ IFTA , remaining predictive by multivariate analysis and independent of humoral markers. One‐year i‐ IFTA was associated with accelerated IF / TA , arterial fibrointimal hyperplasia, and chronic glomerulopathy and with reduced renal function ( P < .001 versus no i‐ IFTA ). In summary, i‐ IFTA is the histologic consequence of active T cell–mediated alloimmunity, representing the interface between inflammation and tubular injury with fibrotic healing. Uncontrolled i‐ IFTA is associated with adverse structural and functional outcomes.