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

Area of Science:

• Nephrology
• Pathology
• Clinical Research

Background:

• The Cure Glomerulonephropathy (CureGN) study is an observational cohort examining minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and IgA nephropathy.
• Accurate documentation of kidney pathology is crucial for understanding disease progression and treatment response.

Purpose of the Study:

• To develop and validate a consensus-based scoring system for kidney biopsy pathology within the CureGN study.
• To assess the reproducibility of the scoring system across multiple pathologists.
• To evaluate the correlation between documented pathologic features and clinical parameters at the time of biopsy.

Main Methods:

• A standardized protocol was created to define and semiquantitatively score glomerular, tubular, interstitial, and vascular lesions using digitized slides and immunofluorescence.
• Pathology materials from 800 biopsies were scored by a primary pathologist, with a subset (11.8%) independently scored by a second pathologist.
• Reproducibility was assessed using Gwet's agreement coefficient (AC1), and correlations with clinical data were performed.

Main Results:

• The scoring system demonstrated high reproducibility for most of the 60 evaluated pathology features, with 76.7% achieving excellent agreement (AC1 > 0.8).
• Specific features showed good reproducibility, though some, like mesangial hypercellularity and percent glomeruli with no lesions, had moderate to fair agreement.
• Significant correlations were found between interstitial inflammation, fibrosis, tubular atrophy, and estimated glomerular filtration rate; foot process effacement and urine protein/creatinine ratio; and active crescents and hematuria.

Conclusions:

• The developed consensus-based scoring system exhibits excellent reproducibility for most kidney pathology features, ensuring consistency among pathologists.
• The observed correlations between specific pathologic findings and clinical characteristics validate the utility of this scoring system.
• This approach provides a robust foundation for future clinicopathologic correlation studies and biomarker discovery in glomerular diseases.