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Novel glomerular lipoprotein deposits associated with apolipoprotein E2 homozygosity
Open accessAbstract
Background Hyperlipoproteinemia is occasionally associated with severe glomerular injury caused by abnormal accumulation of lipid in glomeruli, which occurs in conditions such as lipoprotein glomerulopathy (LPG). This study investigates the cases of two siblings with homozygous apolipoprotein (apo) E2 who show unique histologic features, massive proteinuria, and dysbetalipoproteinemia. Methods Histologic studies were performed using renal biopsy specimens. Plasma lipoproteins were extensively characterized. The exons of the apo E genes were sequenced to avoid missing any mutations. Results Histologically, the siblings' condition resembled LPG by light microscopy studies. Electron microscopy studies revealed large lipoid deposits in the paramesangium, subendothelium, and subepithelium of the glomeruli, which were different from LPG in terms of not forming the layered structure resembling a fingerprint even in large lipoprotein thrombi, and mesangial foam cells. Immunohistochemically, the lipoid deposits contained apo E and apo B. These patients did not have either diabetic nephropathy or other known forms of glomerulonephritis. The sequence of exons of the apo E genes revealed homozygosity for apo E2 in both cases. Conclusion The extensive lipoprotein deposition in glomeruli, which resembles LPG, can also occur in apo E2 homozygous individuals, but in a distinct fashion. Because the two cases were siblings, they may have other shared alleles, in addition to the apo E2 allele, that negatively affect processing of lipoproteins and lead to abnormal accumulation of lipoprotein deposits in glomeruli.
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ApoE2 is not expected to lead to LPG, explaining the distinct-to-LPG phenotype of glomerulopathy rarely reported in apoE2 homozygotes.
“Therefore, apoE2 is not expected to lead to LPG, explaining the distinct-to-LPG phenotype of glomerulopathy rarely reported to apoE2 homozygotes (41,42).”
From Thermodynamic destabilization and aggregation propensity as the mechanism behind the association of apoE3 mutants and lipoprotein glomerulopathy (2018) · cites this paper as [41]
The Abstract says apoE2 homozygosity had not been reported in association with LPG, and the Discussion describes the siblings’ glomerulopathy as distinct from LPG. Those passages support the distinction, but they do not establish that apoE2 cannot lead to LPG or that this explains the phenotype; the Discussion treats its mechanism as uncertain. Page numbers are unavailable in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredVery rare cases of glomerulopathy, different from LPG because they are characterized by marked glomerular foam cell infiltration, have been reported in homozygotes for the apoE2 isoform and in most cases have been associated with type III hyperlipoproteinemia.
“Very rare cases of glomerulopathy, which are different from that of LPG, because they are characterized by marked glomerular foam cell infiltration, have been reported in homozygotes for the apoE2 isoform and, in most of the cases, have been associated with type III hyperlipoproteinemia (41,42).”
From Thermodynamic destabilization and aggregation propensity as the mechanism behind the association of apoE3 mutants and lipoprotein glomerulopathy (2018) · cites this paper as [41]
A wide variety of these findings were reported in one case with homozygous apoE2/2.
“A wide variety of these findings were reported in one case with homozygous apoE2/2 [13].”
In some cases of apoE2 homozygote glomerulopathy, non-lamellar lipoprotein thrombi were observed, which is distinct from lipoprotein glomerulopathy.
“In some cases of apoE2 homozygote glomerulopathy, non-lamellar lipoprotein thrombi were observed, which is distinct from lipoprotein glomerulopathy100).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [100]
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Cites
Lipoprotein Glomerulopathy: Glomerular Lipoprotein Thrombi in a Patient With Hyperlipoproteinemia
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Cited by
Sorted by citations
Apolipoprotein E–related glomerular disorders
Saito, T., Matsunaga, A., Fukunaga, M., Nagahama, K., Hara, S., & Muso, E. (2020) · Kidney International · doi:10.1016/j.kint.2019.10.031 · Cited by 77
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Katsarou, M., Stratikos, E., & Chroni, A. (2018) · Journal of Lipid Research · doi:10.1194/jlr.m088732 · Cited by 22
Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features
Matsunaga, A., & Saito, T. (2025) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.65393 · Cited by 14
Wang, R., Zhao, C., Chen, W., Liu, Z., & Xie, F. (2022) · Journal of Medical Case Reports · doi:10.1186/s13256-022-03302-0 · Cited by 5
Koshino, A., Takaeda, C., Matsuno, T., Kitajima, S., Iwata, Y., Sakai, N., Nagahama, K., Niida, Y., Saito, T., Yokoyama, H., et al. (2022) · Case Reports in Nephrology and Dialysis · doi:10.1159/000525086 · Cited by 2
Metadata
- Authors
- Sakatsume, M., Kadomura, M., Sakata, I., Imai, N., Kondo, D., Osawa, Y., Shimada, H., Ueno, M., Miida, T., Nishi, S., Arakawa, M., & Gejyo, F.
- Affiliations
- Niigata University (JP)
- Corresponding author
- Sakatsume, Minoru
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2001-05
- Volume
- 59
- Issue
- 5
- Pages
- 1911-1918
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W2102634039
- Cited by
- 46
- References
- 2
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2019: 3 · 2018: 3 · 2016: 2 · 2014: 3 · 2013: 4 · 2012: 1
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- lipoprotein glomerulopathy, dysbetalipoproteinemia, hyperlipoproteinemia, proteinuria, apolipoprotein B, familial renal disease
- MeSH terms
- Amino Acid Sequence, Apolipoproteins E, Base Sequence, DNA, DNA Mutational Analysis, Female, Genotype, Homozygote, Humans, Hyperlipoproteinemias, Kidney Diseases, Kidney Glomerulus, Lipoproteins, Male, Microscopy, Electron, Middle Aged, Phenotype, DNA Primers, Apolipoprotein E2
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