title: Renal Graft Fibrosis and Inflammation Quantification by an Automated Fourier-Transform Infrared Imaging Technique.
abstract: Renal interstitial fibrosis and interstitial active inflammation are the main histologic features of renal allograft biopsy specimens. Fibrosis is currently assessed by semiquantitative subjective analysis, and color image analysis has been developed to improve the reliability and repeatability of this evaluation. However, these techniques fail to distinguish fibrosis from constitutive collagen or active inflammation. We developed an automatic, reproducible Fourier-transform infrared (FTIR) imaging-based technique for simultaneous quantification of fibrosis and inflammation in renal allograft biopsy specimens. We generated and validated a classification model using 49 renal biopsy specimens and subsequently tested the robustness of this classification algorithm on 166 renal grafts. Finally, we explored the clinical relevance of fibrosis quantification using FTIR imaging by comparing results with renal function at 3 months after transplantation (M3) and the variation of renal function between M3 and M12. We showed excellent robustness for fibrosis and inflammation classification, with >90% of renal biopsy specimens adequately classified by FTIR imaging. Finally, fibrosis quantification by FTIR imaging correlated with renal function at M3, and the variation in fibrosis between M3 and M12 correlated well with the variation in renal function over the same period. This study shows that FTIR-based analysis of renal graft biopsy specimens is a reproducible and reliable label-free technique for quantifying fibrosis and active inflammation. This technique seems to be more relevant than digital image analysis and promising for both research studies and routine clinical practice.
authors.affiliation: Matrice Extracellulaire et Dynamique Cellulaire Unit, Centre National pour la Recherche Scientifique, Unité Mixte de Recherche 7369, and Nephrology and Renal Transplantation Department and Biopathology Laboratory, Centre Hospitalier et Universitaire de Reims, Reims, France vvuiblet@chu-reims.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Vuiblet
authors.affiliation: Matrice Extracellulaire et Dynamique Cellulaire Unit, Centre National pour la Recherche Scientifique, Unité Mixte de Recherche 7369, and.
authors.forename: Michael
authors.initials: M
authors.lastname: Fere
authors.affiliation: Matrice Extracellulaire et Dynamique Cellulaire Unit, Centre National pour la Recherche Scientifique, Unité Mixte de Recherche 7369, and.
authors.forename: Cyril
authors.initials: C
authors.lastname: Gobinet
authors.affiliation: Biopathology Laboratory, Centre Hospitalier et Universitaire de Reims, Reims, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Birembaut
authors.affiliation: Matrice Extracellulaire et Dynamique Cellulaire Unit, Centre National pour la Recherche Scientifique, Unité Mixte de Recherche 7369, and Cellular and Tissular Imaging Platform, Université de Reims Champagne-Ardenne, Reims, France; and.
authors.forename: Olivier
authors.initials: O
authors.lastname: Piot
authors.affiliation: Matrice Extracellulaire et Dynamique Cellulaire Unit, Centre National pour la Recherche Scientifique, Unité Mixte de Recherche 7369, and Nephrology and Renal Transplantation Department and.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rieu
mesh_terms: D005260:Female; D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000473:pathology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000473:pathology*; D012189:Retrospective Studies; D017550:Spectroscopy, Fourier Transform Infrared
keywords: acute rejection; chronic allograft nephropathy; histopathology; interstitial fibrosis; renal pathology; renal transplantation