Inflammation in areas of fibrosis: The DeKAF prospective cohort

Arthur J. Matas, Erika S. Helgeson, Robert Gaston, Fernando Cosio, Roslyn Mannon, Bertram L. Kasiske, Lawrence Hunsicker, Sita Gourishankar, David Rush, J. Michael Cecka, John Connett, Joseph P. Grande

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Inflammation in areas of fibrosis (i-IFTA) in posttransplant biopsy specimens has been associated with decreased death-censored graft survival (DC-GS). Additionally, an i-IFTA score ≥ 2 is part of the diagnostic criteria for chronic active TCMR (CA TCMR). We examined the impact of i-IFTA and t-IFTA (tubulitis in areas of atrophy) in the first biopsy for cause after 90 days posttransplant (n = 598); mean (SD) 1.7 ± 1.4 years posttransplant. I-IFTA, present in 196 biopsy specimens, was strongly correlated with t-IFTA, and Banff i. Of the 196, 37 (18.9%) had a previous acute rejection episode; 96 (49%) had concurrent i score = 0. Unlike previous studies, i-IFTA = 1 (vs 0) was associated with worse 3-year DC-GS: (i-IFTA = 0, 81.7%, [95% CI 77.7 to 85.9%]); i-IFTA = 1, 68.1%, [95% CI 59.7 to 77.6%]; i-IFTA = 2, 56.1%, [95% CI 43.2 to 72.8%], i-IFTA = 3, 48.5%, [95% CI 31.8 to 74.0%]). The association of i-IFTA with decreased DC-GS remained significant when adjusted for serum creatinine at the time of the biopsy, Banff i, ci and ct, C4d and DSA. T-IFTA was similarly associated with decreased DC-GS. Of these indication biopsies, those with i-IFTA ≥ 2, without meeting other criteria for CA TCMR had similar postbiopsy DC-GS as those with CA TCMR. Those with i-IFTA = 1 and t ≥ 2, ti ≥ 2 had postbiopsy DC-GS similar to CA TCMR. Biopsies with i-IFTA = 1 had similar survival as CA TCMR when biopsy specimens also met Banff criteria for TCMR and/or AMR. Studies of i-IFTA and t-IFTA in additional cohorts, integrating analyses of Banff scores meeting criteria for other Banff diagnoses, are needed.

Original languageEnglish (US)
Pages (from-to)2509-2521
Number of pages13
JournalAmerican Journal of Transplantation
Volume20
Issue number9
DOIs
StatePublished - Sep 1 2020

Bibliographical note

Funding Information:
We thank Astellas, Bristol‐Myers Squibb, Novartis, Pfizer, and Sanofi‐Aventis for unrestricted grants that supported this research. We thank Stephanie Taylor for editorial assistance and preparation of the manuscript.

Funding Information:
We thank Astellas, Bristol-Myers Squibb, Novartis, Pfizer, and Sanofi-Aventis for unrestricted grants that supported this research. We thank Stephanie Taylor for editorial assistance and preparation of the manuscript.

Publisher Copyright:
© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons

Keywords

  • Interstitial fibrosis and tubular atrophy
  • classification systems: Banff classification
  • clinical research/practice
  • kidney transplantation/nephrology
  • pathology/histopathology

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