Banff Fibrosis Study: Multicenter Visual Assessment and Computerized Analysis of Interstitial Fibrosis in Kidney Biopsies

Abstract

Increasing interstitial fibrosis (IF) in native and kidney transplant biopsies is associated with functional decline and serves as a clinical trial end point. A Banff 2009 Conference survey revealed a range in IF assessment practices. Observers from multiple centers were asked to assess 30 renal biopsies with a range of IF and quantitate IF using two approaches on trichrome, Periodic acid-Schiff (PAS) and computer-assisted quantification of collagen III immunohistochemistry (C-IHC) slides, as well as assessing percent of cortical tubular atrophy% (TA%) and Banff total cortical inflammation score (ti-score). C-IHC using whole slide scans was performed. C-IHC assessment showed a higher correlation with organ function (r ¼ À0.48) than did visual assessments (r ¼ À0.32-À0.42); computerized and visual C-IHC assessment also correlated (r ¼ 0.64-0.66). Visual assessment of trichrome and C-IHC showed better correlations with organ function and C-IHC, than PAS, TA% and ti-score. However, visual assessment of IF, independent of approach, was variable among observers, and differences in correlations with organ function were not statistically significant among C-IHC image analysis and visual assessment methods. C-IHC image analysis correlated among three centers (r > 0.90, p < 0.0001, between all centers). Given the difficulty of visual IF assessment standardization, C-IHC image could potentially accomplish standardized IF assessment in multicenter settings.

Whole Slide Imaging for Analytical Anatomic Pathology and Telepathology: Practical Applications Today, Promises, and Perils

“…40,41,60,61 Renal fibrosis IA can measure renal fibrosis in trichrome, periodic acid-Schiff, Sirius red, and collagen III IHC stains. 15,62 Renal tumor classification IA can potentially be used for Fuhrrman grading of renal cell carcinoma, particularly after image normalization.…”

“…61 Providing surrogate markers of allograft deterioration has been a goal of our department in studies using IA to measure renal fibrosis (Figure 1, A through H) in sections stained with trichrome, periodic acid-Schiff, Sirius red, and collagen III for IHC. 15,62 Some of these studies have indicated that IA may provide benefits, given the challenge of standardizing fibrosis assessment among a number of reviewers in multicenter settings. 15 Individuals in our department have collaborated with informatics specialists to devise ways for computers to determine the Fuhrman grade of renal cell carcinoma 63 and to normalize images of renal tumors so that they can be interpreted by computer algorithms.…”

“…15,62 Some of these studies have indicated that IA may provide benefits, given the challenge of standardizing fibrosis assessment among a number of reviewers in multicenter settings. 15 Individuals in our department have collaborated with informatics specialists to devise ways for computers to determine the Fuhrman grade of renal cell carcinoma 63 and to normalize images of renal tumors so that they can be interpreted by computer algorithms. 64 In another study, 65 the mean epidermal growth factor staining density measured by IA correlated with skin adjacent to hypospadias.…”

“…For example, we have conducted international multiobserver agreement studies that have been facilitated through the use of WSIs. [15][16][17] In a study of gallbladder epithelial atypia and early gallbladder cancer staging, WSI was used to circulate cases among 18 experts. If WSIs had not been used, boxes of slides would have had to be transferred from one expert to another; this would have been costly and would have taken approximately 2 years.…”

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“…6,33 Although there are many different causative pathologies, both kidney disease and eventual graft failure are associated with inflammation and fibrosis, the latter characterized by excess connective tissue deposition. 2,34,35 Chronic injury leads to scarring with excessive myofibroblast proliferation and consequent production of ECM proteins, particularly collagens.…”