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Updated: Jun 9, 2026
06:39
Glomerular Outgrowth as an Ex Vivo Assay to Analyze Pathways Involved in Parietal Epithelial Cell Activation
Published on: August 19, 2020
Thin Glomerular Basement Membrane Phenotypes With No Identified Pathogenic COL4A3/A4/A5 Variant
Cristian V Riella1, Dan A Colombo1, Helmut G Rennke2
1Division of Nephrology and Hypertension, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Kidney International Reports
|June 8, 2026
Summary
Genetic testing for COL4A3/A4/A5 variants has limited diagnostic yield in thin glomerular basement membrane (GBM) disease. Most patients with thin GBM lack COL4A variants, underscoring the continued need for kidney biopsy in diagnosis.
Area of Science:
- Nephrology
- Genetics
- Pathology
Background:
- Pathogenic variants in COL4A3/A4/A5 genes are associated with thin glomerular basement membrane (GBM) and Alport syndrome.
- The diagnostic utility of genetic testing for these conditions is not fully established.
Purpose of the Study:
- To evaluate the diagnostic yield of genetic testing in patients with thin GBM.
- To correlate genotype with GBM thickness and other clinical parameters.
Main Methods:
- Retrospective analysis of 115 patients with kidney biopsy and genetic testing on a 385-gene panel.
- Correlation of GBM ultrastructure, estimated glomerular filtration rate, proteinuria, and hematuria with genetic findings.
Main Results:
- Nine patients (19.1%) with ultrastructural GBM abnormalities had pathogenic/likely pathogenic COL4A variants; nine additional patients had variants of uncertain significance (VUS).
- Thirty-one patients (66%) with thin GBM were wildtype for COL4A genes, with some harboring variants in other kidney disease genes.
- COL4A variants correlated with GBM thickness but not other clinical parameters.
Conclusions:
- Two-thirds of patients with thin GBM lack COL4A variants, indicating limited diagnostic yield for genetic testing alone.
- Kidney biopsy remains essential for diagnosing thin GBM and related kidney diseases, even with genetic testing availability.
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