Cure Glomerulonephropathy Pathology Classification and Core Scoring Criteria, Reproducibility, and Clinicopathologic Correlations

Introduction: Cure Glomerulonephropathy (CureGN) is an observational cohort study of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), or IgA nephropathy. We developed a conventional, consensus-based scoring system to document patholo...

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Main Authors: Matthew B Palmer, Virginie Royal, J. Charles Jennette, Abigail R. Smith, Qian Liu, Josephine M. Ambruzs, Nicole K. Andeen, Vivette D. D’Agati, Agnes B. Fogo, Joseph Gaut, Rasheed A. Gbadegesin, Larry A. Greenbaum, Jean Hou, Margaret E Helmuth, Richard A. Lafayette, Helen Liapis, Bruce Robinson, Michael B. Stokes, Katherine Twombley, Hong Yin, Cynthia C. Nast
Format: Article
Language:English
Published: Karger Publishers 2023-10-01
Series:Glomerular Diseases
Subjects:
Online Access:https://beta.karger.com/Article/FullText/534755
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author Matthew B Palmer
Virginie Royal
J. Charles Jennette
Abigail R. Smith
Qian Liu
Josephine M. Ambruzs
Nicole K. Andeen
Vivette D. D’Agati
Agnes B. Fogo
Joseph Gaut
Rasheed A. Gbadegesin
Larry A. Greenbaum
Jean Hou
Margaret E Helmuth
Richard A. Lafayette
Helen Liapis
Bruce Robinson
Michael B. Stokes
Katherine Twombley
Hong Yin
Cynthia C. Nast
author_facet Matthew B Palmer
Virginie Royal
J. Charles Jennette
Abigail R. Smith
Qian Liu
Josephine M. Ambruzs
Nicole K. Andeen
Vivette D. D’Agati
Agnes B. Fogo
Joseph Gaut
Rasheed A. Gbadegesin
Larry A. Greenbaum
Jean Hou
Margaret E Helmuth
Richard A. Lafayette
Helen Liapis
Bruce Robinson
Michael B. Stokes
Katherine Twombley
Hong Yin
Cynthia C. Nast
author_sort Matthew B Palmer
collection DOAJ
description Introduction: Cure Glomerulonephropathy (CureGN) is an observational cohort study of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), or IgA nephropathy. We developed a conventional, consensus-based scoring system to document pathologic features for application across multiple pathologists and herein describe the protocol, reproducibility, and correlation with clinical parameters at biopsy. Methods: Definitions were established for glomerular, tubular, interstitial, and vascular lesions evaluated semiquantitatively using digitized light microscopy slides and electron micrographs, and reported immunofluorescence. Cases with curated pathology materials as of April 2019 were scored by a randomly assigned pathologist, with at least 10% of cases scored by a second pathologist. Scoring reproducibility was assessed using Gwet’s agreement coefficient (AC)1 statistic and correlations with clinical variables were performed. Results: Of 800 scored biopsies (134 MCD, 194 FSGS, 206 MN, 266 IgA), 94 were scored twice (11.8%). Of 60 pathology features, 46 (76.7%) demonstrated excellent (AC1>0.8), and 12 (20.0%) had good (AC1 0.6–0.8) reproducibility. Mesangial hypercellularity scored as absent, focal, or diffuse had moderate reproducibility (AC1 = 0.58), but good reproducibility (AC1 = 0.71) when scored as absent or focal versus diffuse. The percent glomeruli scored as no lesions had fair reproducibility (AC1 = 0.34). Strongest correlations between pathologic features and clinical characteristics at biopsy included interstitial inflammation, interstitial fibrosis, and tubular atrophy with estimated glomerular filtration rate, foot process effacement with urine protein/creatinine ratio, and active crescents with hematuria. Conclusions: Most scored pathology features showed excellent reproducibility, demonstrating consistency for these features across multiple pathologists. Correlations between certain pathologic features and expected clinical characteristics show the value of this approach for future studies on clinicopathologic correlations and biomarker discovery.
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spelling doaj.art-f1cb4212a72b410bafd61bc67ce531342023-11-23T07:16:30ZengKarger PublishersGlomerular Diseases2673-36332023-10-013124825710.1159/000534755534755Cure Glomerulonephropathy Pathology Classification and Core Scoring Criteria, Reproducibility, and Clinicopathologic CorrelationsMatthew B Palmer0Virginie Royal1J. Charles Jennette2Abigail R. Smith3Qian Liu4Josephine M. Ambruzs5Nicole K. Andeen6Vivette D. D’Agati7Agnes B. Fogo8Joseph Gaut9Rasheed A. Gbadegesin10Larry A. Greenbaum11Jean Hou12Margaret E Helmuth13Richard A. Lafayette14Helen Liapis15Bruce Robinson16Michael B. Stokes17Katherine Twombley18Hong Yin19Cynthia C. Nast20Department of Pathology, University of Pennsylvania, Philadelphia, PA, USADepartment of Pathology, Hospital Maisonneuve-Rosemont, University of Montreal, Montreal, QC, CanadaDepartment of Pathology, University of North Carolina Kidney Center, Chapel Hill, NC, USAArbor Research Collaborative for Health, Ann Arbor, MI, USAArbor Research Collaborative for Health, Ann Arbor, MI, USAArkana Laboratories, Little Rock, AR, USADepartment of Pathology, Oregon Health and Science University, Portland, OR, USADepartment of Pathology, Columbia University, New York, NY, USADepartment of Pathology, Vanderbilt University, Nashville, TN, USADepartment of Pathology, Washington University, St. Louis, MO, USADivision of Nephrology, Duke Children’s Hospital Medical Center, Durham, NC, USADivision of Nephrology, Department of Pediatrics, Emory University, Atlanta, GA, USADepartment of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USAArbor Research Collaborative for Health, Ann Arbor, MI, USADivision of Nephrology, Department of Medicine, Stanford University, Stanford, CA, USANephrology Center, Ludwig Maximilian University, Munich, GermanyArbor Research Collaborative for Health, Ann Arbor, MI, USADepartment of Pathology, Columbia University, New York, NY, USADivision of Nephrology, Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USAPathology, Children’s Healthcare of Atlanta, Atlanta, GA, USADepartment of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USAIntroduction: Cure Glomerulonephropathy (CureGN) is an observational cohort study of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), or IgA nephropathy. We developed a conventional, consensus-based scoring system to document pathologic features for application across multiple pathologists and herein describe the protocol, reproducibility, and correlation with clinical parameters at biopsy. Methods: Definitions were established for glomerular, tubular, interstitial, and vascular lesions evaluated semiquantitatively using digitized light microscopy slides and electron micrographs, and reported immunofluorescence. Cases with curated pathology materials as of April 2019 were scored by a randomly assigned pathologist, with at least 10% of cases scored by a second pathologist. Scoring reproducibility was assessed using Gwet’s agreement coefficient (AC)1 statistic and correlations with clinical variables were performed. Results: Of 800 scored biopsies (134 MCD, 194 FSGS, 206 MN, 266 IgA), 94 were scored twice (11.8%). Of 60 pathology features, 46 (76.7%) demonstrated excellent (AC1>0.8), and 12 (20.0%) had good (AC1 0.6–0.8) reproducibility. Mesangial hypercellularity scored as absent, focal, or diffuse had moderate reproducibility (AC1 = 0.58), but good reproducibility (AC1 = 0.71) when scored as absent or focal versus diffuse. The percent glomeruli scored as no lesions had fair reproducibility (AC1 = 0.34). Strongest correlations between pathologic features and clinical characteristics at biopsy included interstitial inflammation, interstitial fibrosis, and tubular atrophy with estimated glomerular filtration rate, foot process effacement with urine protein/creatinine ratio, and active crescents with hematuria. Conclusions: Most scored pathology features showed excellent reproducibility, demonstrating consistency for these features across multiple pathologists. Correlations between certain pathologic features and expected clinical characteristics show the value of this approach for future studies on clinicopathologic correlations and biomarker discovery.https://beta.karger.com/Article/FullText/534755cure glomerulonephropathykidney biopsyreproducibilitypathology scoringclinical-pathologic correlation
spellingShingle Matthew B Palmer
Virginie Royal
J. Charles Jennette
Abigail R. Smith
Qian Liu
Josephine M. Ambruzs
Nicole K. Andeen
Vivette D. D’Agati
Agnes B. Fogo
Joseph Gaut
Rasheed A. Gbadegesin
Larry A. Greenbaum
Jean Hou
Margaret E Helmuth
Richard A. Lafayette
Helen Liapis
Bruce Robinson
Michael B. Stokes
Katherine Twombley
Hong Yin
Cynthia C. Nast
Cure Glomerulonephropathy Pathology Classification and Core Scoring Criteria, Reproducibility, and Clinicopathologic Correlations
Glomerular Diseases
cure glomerulonephropathy
kidney biopsy
reproducibility
pathology scoring
clinical-pathologic correlation
title Cure Glomerulonephropathy Pathology Classification and Core Scoring Criteria, Reproducibility, and Clinicopathologic Correlations
title_full Cure Glomerulonephropathy Pathology Classification and Core Scoring Criteria, Reproducibility, and Clinicopathologic Correlations
title_fullStr Cure Glomerulonephropathy Pathology Classification and Core Scoring Criteria, Reproducibility, and Clinicopathologic Correlations
title_full_unstemmed Cure Glomerulonephropathy Pathology Classification and Core Scoring Criteria, Reproducibility, and Clinicopathologic Correlations
title_short Cure Glomerulonephropathy Pathology Classification and Core Scoring Criteria, Reproducibility, and Clinicopathologic Correlations
title_sort cure glomerulonephropathy pathology classification and core scoring criteria reproducibility and clinicopathologic correlations
topic cure glomerulonephropathy
kidney biopsy
reproducibility
pathology scoring
clinical-pathologic correlation
url https://beta.karger.com/Article/FullText/534755
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