Long-Term Clinical Course of COL4A1-Associated Nephropathy and Assessment of α1 Chain of Type IV Collagen Expression in Kidney Biopsy Specimens: A Case Report

This is the authors' abstract. We don't add key points for this paper.

COL4A1 variants cause a spectrum of systemic disorders encompassed by Gould syndrome. While kidney involvement is recognized, its long-term progression and detailed kidney pathology remain uncharacterized. We present a 39-year-old man with a heterozygous p.G1239R COL4A1 variant, persistent microscopic hematuria, and a progressive eGFR decline of −1.2 mL/min/1.73 m 2 per year over a 10-year follow-up. Light microscopy showed only focal global glomerulosclerosis and mild tubular dilatation. Immunofluorescence for the α1 chain of type IV collagen (α1[IV]) revealed reduced signal intensity in the tubular basement membrane (TBM). Electron microscopy demonstrated focal thinning of the glomerular basement membrane (GBM), and heterogeneous abnormalities including thinning, focal thickening, reticulation, and lamellation of TBM. Immunoelectron microscopy using FluoroNanogold showed decreased density of gold particles in the TBM, correlating with the fluorescence intensity. This report analyzes COL4A1 expression using correlative light and electron microscopy (CLEM), and describes the long-term kidney function decline. In patients with hematuria and a thin GBM, in addition to Alport syndrome, COL4A1 -associated nephropathy should also be considered. Recognizing this entity is essential for accurate systemic risk assessment and genetic counseling. Semi-quantitative assessment of COL4A1 expression in biopsy specimens using CLEM may be a key diagnostic tool for patients with heterozygous COL4A1 variants.