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Abstract: PO1936

Pathology Core Scoring Parameters and Reproducibility in the CureGN Study

Session Information

Category: Pathology and Lab Medicine

  • 1600 Pathology and Lab Medicine

Authors

  • Smith, Abigail R., Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States
  • Palmer, Matthew, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Royal, Virginie, Universite de Montreal, Montreal, Quebec, Canada
  • Liu, Qian, Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States
  • Andeen, Nicole K., Oregon Health & Science University School of Medicine, Portland, Oregon, United States
  • Avila-Casado, Carmen, University of Toronto, Toronto, Ontario, Canada
  • Bagnasco, S.M., Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • D'Agati, Vivette D., Columbia University Irving Medical Center, New York, New York, United States
  • Fogo, Agnes B., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Gaut, Joseph, Washington University in St Louis School of Medicine, St Louis, Missouri, United States
  • Gbadegesin, Rasheed A., Duke University School of Medicine, Durham, North Carolina, United States
  • Greenbaum, Larry A., Emory University, Atlanta, Georgia, United States
  • Hou, Jean, Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Lafayette, Richard A., Stanford Medicine, Stanford, California, United States
  • Liapis, Helen, Washington University in St Louis School of Medicine, St Louis, Missouri, United States
  • Parsa, Afshin, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
  • Robinson, Bruce M., Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States
  • Stokes, Michael Barry, Columbia University Irving Medical Center, New York, New York, United States
  • Twombley, Katherine, Medical University of South Carolina, Charleston, South Carolina, United States
  • Zee, Jarcy, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Jennette, J. Charles, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States
  • Nast, Cynthia C., Cedars-Sinai Medical Center, Los Angeles, California, United States
Background

CureGN is an NIH-funded multi-center, prospective, observational cohort study of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), or IgA nephropathy from 66 international sites with 2500 enrolled participants. The large scale of CureGN requires a practical systematic approach to pathologic scoring that can be applied consistently across a large number of cases and multiple scoring pathologists. The method reflects common pathology practices, generating data for assignment to currently used disease classifications and use in future studies utilizing conventional parameters. The objective of this analysis was to determine and evaluate the pathology scoring reproducibility.

Methods

The CureGN Core Scoring Workgroup established definitions of multiple glomerular, tubular, interstitial and vascular lesions evaluated semi-quantitatively, as observed by light, immunofluorescence, and electron microscopy (EM). All cases with complete pathology data as of April 2019 were randomly assigned for scoring of whole slide and EM images to one of eleven pathologists; a random subset of >10% were scored by a second pathologist. Reproducibility was assessed using Gwet’s AC1 statistic.

Results

Of 797 biopsy specimens (141 MCD, 186 FSGS, 205 MN, 265 IgA) scored by at least one pathologist, 94 were scored twice (12%). Of 60 pathology features, 46 (77%) demonstrated excellent reproducibility (Gwet’s AC1>0.8), and 12 (20%) had good reproducibility (Gwet’s AC1>0.6). Mesangial hypercellularity scored as absent, focal or diffuse had moderate reproducibility (AC1=0.58), but scored as absent vs present had AC1=0.71. The percent glomeruli scored as having no lesions had fair reproducibility (AC1=0.34).

Conclusion

The majority of pathologic features scored showed excellent reproducibility, supporting the hypothesis that these features can be scored consistently by multiple pathologists. Future studies will include correlation of these histopathologic features with clinical and demographic characteristics at the time of biopsy and eventually disease biomarkers and clinical outcomes.

Funding

  • NIDDK Support