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

Am J Transplant. 2018 Feb;18(2):364-376. doi: 10.1111/ajt.14609. Epub 2018 Jan 3.


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.

Keywords: classification systems: Banff classification; clinical research/practice; immunosuppressive regimens; kidney transplantation/nephrology; pathology/histopathology; rejection: T cell-mediated (TCMR).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Fibrosis / immunology
  • Fibrosis / pathology*
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / etiology*
  • Graft Rejection / pathology
  • Graft Survival
  • Histocompatibility
  • Humans
  • Inflammation / immunology
  • Inflammation / pathology*
  • Isoantibodies
  • Kidney Diseases / immunology
  • Kidney Diseases / pathology*
  • Kidney Diseases / surgery
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects*
  • Kidney Tubules / immunology
  • Kidney Tubules / pathology*
  • Longitudinal Studies
  • Male
  • Postoperative Complications*
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology


  • Isoantibodies