Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 18, Issue 2, Pages 364-376Publisher
WILEY
DOI: 10.1111/ajt.14609
Keywords
classification systems: Banff classification; clinical research/practice; immunosuppressive regimens; kidney transplantation/nephrology; pathology/histopathology; rejection: T-cellmediated (TCMR)
Categories
Funding
- Commonwealth Government of Australia
Ask authors/readers for more resources
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. This longitudinal cohort study concludes that i-IFTA was the histological consequence of active T cell-mediated alloimmunity, representing the interface between inflammation and tubular injury, and followed by adverse structural and functional outcomes. See related articles on pages 293, 321, and 377.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available