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The causes, significance and consequences of inflammatory fibrosis in kidney transplantation: The Banff i-IFTA lesion

2017; Elsevier BV; Volume: 18; Issue: 2 Linguagem: Inglês

10.1111/ajt.14609

1600-6143

Brian J. Nankivell, Meena Shingde, Karen Keung, Caroline Fung, Richard Borrows, Philip J. O’Connell, Jeremy R. Chapman,

Transplantation: Methods and Outcomes

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. 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.