Renal Medullary and Cortical Correlates in Fibrosis, Epithelial Mass, Microvascularity, and Microanatomy Using Whole Slide Image Analysis Morphometry

• Type of Material: Article
• Authors: Alton Farris III, Emory University; Carla Ellis, Emory University; Thomas Rogers, Emory University; Diane Lawson, Emory University; Cynthia Cohen, Emory University; Seymour Rosen, Harvard University
• Language: English
• Date: 2016-08-30
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Farris et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0161019
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 11
• Issue: 8
• Start Page: e0161019
• End Page: e0161019
• Keywords: ARCHITECTURE; BIOPSY; KIDNEY FIBROSIS; Creatinine; NEPHROPATHY; Collagens; Immunohistochemistry techniques; MESENCHYMAL TRANSITION; PROGRESSION; Biopsy; FUNCTIONAL-ASPECTS; Multidisciplinary Sciences; Science & Technology; Atrophy; Image analysis; Morphometry; Fibrosis; FIBROBLASTS; INTERSTITIAL FIBROSIS; COMPLICATIONS
• Research Categories: Health Sciences, Pathology

Abstract

Renal tubulointerstitial injury often leads to interstitial fibrosis and tubular atrophy (IF/TA). IF/TA is typically assessed in the renal cortex and can be objectively quantitated with computerized image analysis (IA). However, the human medulla accounts for a substantial proportion of the nephron; therefore, medullary scarring will have important cortical consequences and may parallel overall chronic renal injury. Trichrome, periodic acid-Schiff (PAS), and collagen III immunohistochemistry (IHC) were visually examined and quantitated on scanned whole slide images (WSIs) (N = 67 cases). When tuned to measure fibrosis, IA of trichrome and Trichrome-PAS (T-P) WSIs correlated for all anatomic compartments (among cortex, medulla, and entire tissue, r = 0.84 to 0.89, P all <0.0001); and collagen III deposition correlated between compartments (r = 0.69 to 0.89, P <0.0001 to 0.0002); however, trichrome and T-P measures did not correlate with collagen deposition, suggesting heterogeneous contributions to extracellular matrix deposition. Epithelial cell mass (EPCM) correlated between cortex and medulla when measured with cytokeratin IHC and with the trichrome red portion (r = 0.85 and 0.66, respectively, all P < 0.0001). Visual assessment also correlated between compartments for fibrosis and EPCM. Correlations were found between increasing medullary inner stripe (IS) width and fibrosis in all of the tissue and the medulla by trichrome morphometry (r = 0.56, P < 0.0001, and r = 0.48, P = 0.00008, respectively). Weak correlations were found between increasing IS width and decreasing visual assessment of all tissue EPCM. Microvessel density (MVD) and microvessel area (MVA) measured using a MVD algorithm applied to CD34 IHC correlated significantly between all compartments (r = 0.76 to 0.87 for MVD and 0.71 to 0.87 for MVA, P all < 0.0001). Overall, these findings demonstrate the interrelatedness of the cortex and medulla and the importance of considering the renal parenchyma as a whole.