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. 2023 Oct 26;3(1):248-257.
doi: 10.1159/000534755. eCollection 2023 Jan-Dec.

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

Matthew B Palmer  1 , Virginie Royal  2 , J Charles Jennette  3 , Abigail R Smith  4 , Qian Liu  4 , Josephine M Ambruzs  5 , Nicole K Andeen  6 , Vivette D D'Agati  7 , Agnes B Fogo  8 , Joseph Gaut  9 , Rasheed A Gbadegesin  10 , Larry A Greenbaum  11 , Jean Hou  12 , Margaret E Helmuth  4 , Richard A Lafayette  13 , Helen Liapis  14 , Bruce Robinson  4 , Michael B Stokes  7 , Katherine Twombley  15 , Hong Yin  16 , Cynthia C Nast  12 ; CureGN Consortium
Affiliations

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

Matthew B Palmer et al. Glomerular Dis. .

Abstract

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.

Keywords: Clinical-pathologic correlation; Cure Glomerulonephropathy; Kidney biopsy; Pathology scoring; Reproducibility.

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Conflict of interest statement

The authors declare that they have no relevant financial interests or conflicts of interest.

Figures

Fig. 1.
Fig. 1.
Inter-agreement statistics using ICC or Gwet’s AC for 94 cases included in reproducibility analysis. The numbers on the right side of the plot are percent of nonzero values to show the prevalence of the ordinal pathology parameters (NA is shown for categorical parameters because percent of nonzero is not applicable). Standard error bars are shown for Gwet’s AC statistics. Agreement statistics ≥0.6 are plotted in green and those <0.6 are plotted in red. Agreement statistics for parameters agreement statistics ≥0.6 and <10% nonzero values are in yellow. The two features with agreement statistics <0.6 both had >10% nonzero values. Glom, glomerular; TIV, tubulointerstitial and vascular; IF, immunofluorescence; EM, electron microscopy; ICC, intraclass correlation coefficient.
Fig. 2.
Fig. 2.
Pathology parameters with strongest correlation with baseline or clinical characteristics. IF, immunofluorescence; EM, electron microscopy; IgA score, immunoglobulin A intensity by immunofluorescence; LM, light microscopy; UPCR, urine protein‐to‐creatinine ratio; eGFR, estimated glomerular filtration rate; albumin, serum albumin.
See this image and copyright information in PMC

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