Seeing the Unseen in Renal Pathology: Leveraging Electron Microscopy Analysis to unveil the Diagnostic Nuances of Alport Syndrome

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Seeing the Unseen in Renal Pathology: Leveraging Electron Microscopy Analysis to unveil the Diagnostic Nuances of Alport Syndrome

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Author(s): Li Shan Ong ¹

Publication date (Electronic): 21 January 2025

Conference name: 13th Asia Pacific Microscopy Congress 2025 (APMC13)

Conference date: 2-7 Febuary 2025

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Abstract

In diagnostic pathology, the most conventional approach is to use a light microscope to study, investigate, and assess cells and tissues at a microscopic level. However, light microscopy has inherent limitations in terms of its resolution, restricting what can be observed through the lens. To overcome these limitations, electron microscopy was first utilised in the mid 20 ^th century to further complement light microscopy in diagnosing various pathologies. Unlike light microscopes, electron microscopes provide highly magnified and detailed images of individual cells and subcellular structures, revealing features beyond the reach of the human eye. This capability is especially critical and valuable in diagnosing renal pathologies that could not be definitively differentiated with light microscopy alone. For instance, Alport Syndrome as one of the renal pathologies, relies heavily on electron microscopy to identify the ultrastructural abnormalities essential for an accurate diagnosis and effective prognosis. Alport Syndrome is classified as a hereditary renal disease caused by the abnormalities of the type IV collagen network of basement membrane in the glomerulus located within kidney cortex ( 1). Early diagnosis using TEM is advantageous, as this disease encompasses a range of renal involvement from mild to progressive nephropathy. This progression often leads to chronic kidney disease (CKD) and end-stage renal disease (ESRD) and could be associated with sensorineural hearing loss and specific ocular abnormalities ( 2). TEM enables detailed examination of the glomerular basement membrane (GBM) where Alport Syndrome presents with a characteristic pattern of irregular thinning and thickening as well as a distinctive “basket-weave” appearance resulted from multilayered and splintered of lamina densa ( 3). Thin glomerular basement membrane nephropathy (TBMN) is often compared to Alport Syndrome, as the similarities are challenging to be distinguished under light microscopy alone ( 4, 5). Through TEM, subtle ultrastructural differences in the GBM can be visualised, enabling precise differentiation.

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Publication date (Electronic): 21 January 2025

Electronic Location Identifier: e132

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[1 ]Medical Scientist, Department of Anatomical Pathology (Electron Microscopy), Monash Medical Centre (Monash Health), Clayton, Victoria, Australia

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DOI: 10.14293/APMC13-2025-0132

SO-VID: 42c33946-c80a-4d7d-b389-c4f488b15c63

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Published under Creative Commons Attribution 4.0 International ( CC BY 4.0). Users are allowed to share (copy and redistribute the material in any medium or format) and adapt (remix, transform, and build upon the material for any purpose, even commercially), as long as the authors and the publisher are explicitly identified and properly acknowledged as the original source.

Conference name: 13th Asia Pacific Microscopy Congress 2025

Conference acronym: APMC13

Conference number: 13

Conference location: Brisbane, Australia

Conference date: 2-7 Febuary 2025

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References

Miner JH, Kidney International volume 86 (2014), issue 6 p. 1081-1083. https://doi.org/10.1038/ki.2014.326
Kashtan, CE, GeneReviews [Online], N/A (2019), https://www.ncbi.nlm.nih.gov/books/NBK1207/
Fogo, AB et al., “AJKD Atlas of Renal Pathology: Alport Syndrome” American Journal of Kidney Disease volume 68 (2016), issue 4 p. 15-16.
Spear, GS and Slusser RJ, The American Journal of Pathology volume 69 (1972), issue 2 p. 213-214.
Haas M, Archives of Pathology and Laboratory Medicine, volume 133 (2009), issue 2 p. 224-32. https://doi.org/10.5858/133.2.224

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[1] Miner JH, Kidney International volume 86 (2014), issue 6 p. 1081-1083. https://doi.org/10.1038/ki.2014.326

[2] Kashtan, CE, GeneReviews [Online], N/A (2019), https://www.ncbi.nlm.nih.gov/books/NBK1207/

[3] Fogo, AB et al., “AJKD Atlas of Renal Pathology: Alport Syndrome” American Journal of Kidney Disease volume 68 (2016), issue 4 p. 15-16.

[4] Spear, GS and Slusser RJ, The American Journal of Pathology volume 69 (1972), issue 2 p. 213-214.

[5] Haas M, Archives of Pathology and Laboratory Medicine, volume 133 (2009), issue 2 p. 224-32. https://doi.org/10.5858/133.2.224

Seeing the Unseen in Renal Pathology: Leveraging Electron Microscopy Analysis to unveil the Diagnostic Nuances of Alport Syndrome

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