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Updated: Nov 24, 2025
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Validation of a Histologic Scoring Index for C3 Glomerulopathy
Fernando Caravaca-Fontán1, Hernando Trujillo2, Marina Alonso3
1Instituto de Investigación Hospital 12 de octubre (i+12), Madrid, Spain; Department of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
Insights
The C3 glomerulopathy histologic index (C3G-HI) was validated to predict kidney failure in C3G patients. The total chronicity score of the C3G-HI independently predicted kidney failure, confirming its prognostic value.
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.
Rationale & Objective:
A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population.
Study Design:
Multicenter, retrospective cohort study.
Setting & Participants:
111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN).
Predictors:
Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score.
Outcome:
Time to kidney failure.
Analytical Approach:
Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines.
Results:
The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure.
Limitations:
Only a subset of the kidney biopsies was centrally reviewed. Residual confounding.
Conclusions:
We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure.
