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Association of Histologic Parameters with Outcome in C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated
Hannah J Lomax-Browne1, Nicholas R Medjeral-Thomas1, Sean J Barbour2
1Department for Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, United Kingdom.
Insights
Kidney diseases like C3 glomerulopathy involve abnormal C3 deposition. Cellular/fibrocellular crescents and interstitial fibrosis/tubular atrophy in kidney biopsies predict worsening kidney function and failure risk.
Area of Science:
- Nephrology
- Pathology
- Complement System Biology
Background:
- C3 glomerulopathy and Ig-associated membranoproliferative GN are kidney diseases.
- Characterized by abnormal glomerular complement C3 deposition.
- Approximately 50% of patients progress to kidney failure within 10 years.
Purpose of the Study:
- To identify patients with poor prognosis in C3 glomerulopathy and Ig-GN.
- To analyze kidney biopsy features and their association with clinical outcomes.
Main Methods:
- Retrospective analysis of 156 native kidney biopsies from 123 patients with C3 glomerulopathy and 33 with Ig-GN.
- Utilized a validated histologic scoring system.
- Employed linear regression, survival analysis, and Cox models.
Main Results:
- Mesangial expansion, endocapillary hypercellularity, and GBM double contours were frequent.
- Cellular/fibrocellular crescents and interstitial fibrosis/tubular atrophy scores were linked to worse eGFR.
- Proteinuria correlated with endocapillary hypercellularity and GBM double contours.
Conclusions:
- Cellular/fibrocellular crescents and interstitial fibrosis/tubular atrophy scores are key predictors of kidney function decline.
- These histologic features significantly determine the risk of progression to kidney failure.
Background And Objectives:
C3 glomerulopathy and idiopathic Ig-associated membranoproliferative GN are kidney diseases characterized by abnormal glomerular complement C3 deposition. These conditions are heterogeneous in outcome, but approximately 50% of patients develop kidney failure within 10 years.
Design, Setting, Participants, & Measurements:
To improve identification of patients with poor prognosis, we performed a detailed analysis of percutaneous kidney biopsies in a large cohort of patients. Using a validated histologic scoring system, we analyzed 156 native diagnostic kidney biopsies from a retrospective cohort of 123 patients with C3 glomerulopathy and 33 patients with Ig-associated membranoproliferative GN. We used linear regression, survival analysis, and Cox proportional hazards models to assess the relationship between histologic and clinical parameters with outcome.
Results:
Frequent biopsy features were mesangial expansion and hypercellularity, glomerular basement membrane double contours, and endocapillary hypercellularity. Multivariable analysis showed negative associations between eGFR and crescents, interstitial inflammation, and interstitial fibrosis/tubular atrophy. Proteinuria positively associated with endocapillary hypercellularity and glomerular basement membrane double contours. Analysis of second native biopsies did not demonstrate associations between immunosuppression treatment and improvement in histology. Using a composite outcome, risk of progression to kidney failure associated with eGFR and proteinuria at the time of biopsy, cellular/fibrocellular crescents, segmental sclerosis, and interstitial fibrosis/tubular atrophy scores.
Conclusions:
Our detailed assessment of kidney biopsy data indicated that cellular/fibrocellular crescents and interstitial fibrosis/tubular atrophy scores were significant determinants of deterioration in kidney function.
