Validation of a Histologic Scoring Index for C3 Glomerulopathy

Area of Science:

• Nephrology
• Pathology
• Glomerular Diseases

Background:

• C3 glomerulopathy (C3G) is a rare kidney disease characterized by complement C3 deposition in glomeruli.
• A prognostic histologic index (C3G-HI) was previously proposed but requires validation.
• Accurate prediction of disease progression is crucial for managing C3G patients.

Purpose of the Study:

• To validate the performance of the C3G-HI in predicting kidney failure in a new cohort of C3G patients.
• To assess the prognostic value of C3G-HI activity and chronicity scores.

Main Methods:

• Multicenter, retrospective cohort study including 111 C3G patients.
• Histopathological assessment using C3G-HI total activity and chronicity scores.
• Cox proportional hazards analysis to model kidney failure risk.

Main Results:

• The C3G-HI demonstrated good inter-rater reproducibility (ICC=0.63 for activity, 0.89 for chronicity).
• 43% of patients developed kidney failure during a mean follow-up of 65 months.
• The C3G-HI total chronicity score was an independent predictor of kidney failure, while clinical factors like eGFR and proteinuria were also significant.

Conclusions:

• The C3G-HI is a validated tool for predicting kidney failure in C3G.
• The total chronicity score is the primary histologic correlate of kidney failure in C3G.
• This validation supports the use of C3G-HI in clinical practice for C3G prognostication.