The Banff Fibrosis Trial: A Multicenter Trial of Visual Assessment of Interstitial Fibrosis in Kidney Biopsies and Its Relationship to Function
Alton B Farris, Samantha Chan, Jessie Climenhaga, Chris Bellamy, Daniel Seron, Robert Colvin, Michael Mengel. Emory University, Atlanta; University of Alberta, Edmonton, Canada; Edinburgh University, Edinburgh, United Kingdom; University of Barcelona, Barcelona, Spain; MGH, Boston
Background: Interstitial fibrosis (IF) in renal biopsies is a valuable correlate for organ function, provides prognostic information and is a potential end point in clinical trials.
Design: We conducted a multi-centre trial using 15 allograft and 15 native kidney biopsies with a full range of IF. Sections were stained with trichrome, PAS, or IHC for Collagen III, and scans (Aperio) were prepared for scoring. Trichrome and PAS stained slides were assessed by 27 pathologists following two different definitions of IF (figure 1): (A) the % cortex surface occupied with fibrous tissue. (B) the % cortex which has abnormal fibrosis. Reproducibility was assessed using kappa statistics. The results were correlated with collagen III IHC computer based image analysis (reference standard). All five approaches for assessing IF as well as the extent of tubular atrophy and the Banff total cortical inflammation (ti) score, both visually on the PAS stain, were correlated to organ function (GFR).
Results: Using the trichrome stain better correlations with the collagen III IHC were obtained compared to the PAS stain. Approach B, i.e. estimating the % abnormal cortex, was superior to approach A (Table 1). A stronger inverse association between IF and GFR was seen with the trichrome stain, using either A or B methods. Tubular atrophy and the Banff total i-score correlated less well with the collagen III stain and GFR. Independent of the approach and the stain, reproducibility between observers for assessing IF was weak (kappa <0.25 compared to collagen IHC), while the ti score showed fair to moderate reproducibility.
Conclusions: The trichrome stain is superior to the PAS stain in assessing IF. Pathologists are better capable of assessing the extent of abnormal cortex than the extent of interstitial space occupied by fibrous tissue. Visual assessment of IF in a trichrome stains correlates with organ function as well as computer-based image analysis of collagen III IHC. Significant variability between observers argues that more precise consensus criteria are needed for measuring IF visually.
Category: Kidney (does not include tumors)
Tuesday, March 20, 2012 8:00 AM
Platform Session: Section H, Tuesday Morning