Lipoprotein glomerulopathy
Abstract
PURPOSE OF REVIEW: Lipoprotein glomerulopathy is a rare disorder characterized by proteinuria, renal insufficiency and disturbances in lipoprotein metabolism closely related to those observed in type III hyperlipidemia. Rare mutations in apolipoprotein E (apoE) gene may contribute to the pathogenesis of the disease. This article reviews the clinical and laboratory features of lipoprotein glomerulopathy, discusses the mechanisms that may be implicated in its pathogenesis and summarizes the currently available therapeutic options. RECENT FINDINGS: During the past years two new apoE gene mutations were described in Caucasian patients, apoE Modena (Arg150→Cys) and apoE Las Vegas (Ala152→Asp), a finding indicating that the disease may be more common in white populations than initially thought. Results from case studies suggest that fibrates improve renal pathology and may result in the complete clinical remission of the disease. LDL-apheresis or immunoadsorption onto staphylococcal protein A may also have a role in refractory cases. SUMMARY: Lipid glomerulopathy is a rare, poorly understood disorder with potentially detrimental consequences. The determination of the effects of apoE mutations on the structural and functional characteristics of the mature protein may provide new insights in the pathogenesis of the disease. Meanwhile, intensive lipid-lowering may reduce proteinuria and preserve renal function in this patient group.
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Mutated apoE has been proposed as a factor outside the kidney crucial for LPG pathogenesis because LPG is related to inherited apoE gene mutations acting dominantly with incomplete penetrance.
“One such factor has been proposed to be mutated apoE, because LPG has been related with inherited mutations within the apoE gene that act in a dominant way but with incomplete penetrance (1,2,5,6).”
From Thermodynamic destabilization and aggregation propensity as the mechanism behind the association of apoE3 mutants and lipoprotein glomerulopathy (2018) · cites this paper as [2]
APOE (p.Arg150Cys) is correctly identified as APOE (Arg150Cys), the same variant as APOE Modena (Arg150Cys).
“Meanwhile, APOE (p.Arg150Cys)92) is correctly identified as APOE (Arg150Cys), the same variant as APOE Modena (Arg150Cys)78).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [78]
Several rare apoE mutations have been linked to the development of LPG, with the most common and best characterized being apoE Sendai.
“Several rare apoE mutations have been linked to the development of LPG ( 22 ), with the most common and best characterized being apoE Sendai ( 23 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [22]
Several very rare apoE mutants are associated with a progressive glomerular disease, termed LPG, with the most common being apoE Sendai.
“Several very rare apoE mutants are associated with a progressive glomerular disease, termed LPG ( 22 ), with the most common being apoE Sendai ( 32 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [22]
LPG is inherited in an autosomal dominant fashion with incomplete penetrance.
“It is usually caused by a mutation in apolipoprotein E (apoE) and is inherited in an autosomal dominant fashion with incomplete penetrance.3”
From Lipoprotein Glomerulopathy, First Case Report from Canada (2022) · cites this paper as [3]
LPG affects males more commonly than females.
“LPG usually presents as progressively worsening proteinuria in a patient of East Asian descent, with males more commonly affected than females.3”
From Lipoprotein Glomerulopathy, First Case Report from Canada (2022) · cites this paper as [3]
Almost all patients with LPG who receive a kidney transplant have a recurrence of LPG on kidney biopsy within several months.
“Almost all patients with LPG who receive a kidney transplant have a recurrence of LPG on kidney biopsy within several months.3”
From Lipoprotein Glomerulopathy, First Case Report from Canada (2022) · cites this paper as [3]
LPG usually presents as progressively worsening proteinuria in a patient of East Asian descent.
“LPG usually presents as progressively worsening proteinuria in a patient of East Asian descent, with males more commonly affected than females.3”
From Lipoprotein Glomerulopathy, First Case Report from Canada (2022) · cites this paper as [3]
These lipoproteins then accumulate in glomeruli and form lipoprotein thrombi.
“These lipoproteins then accumulate in glomeruli and form lipoprotein thrombi.”
From Lipoprotein Glomerulopathy, First Case Report from Canada (2022) · cites this paper as [3]
A change in binding affinity of apoE to the LDL receptor impairs catabolism of triglyceride-rich lipoproteins.
“A change in binding affinity of the apoE to the LDL receptor impairs catabolism of triglyceride-rich lipoproteins.3”
From Lipoprotein Glomerulopathy, First Case Report from Canada (2022) · cites this paper as [3]
Lipoprotein glomerulopathy (LPG) is caused by a mutation in the apolipoprotein E gene (APOE).
“Lipoprotein glomerulopathy (LPG) is caused by a mutation in the apolipoprotein E gene (APOE) gene and is characterized by lipoprotein thrombi in glomerular capillaries.”
From Lipoprotein Glomerulopathy, First Case Report from Canada (2022) · cites this paper as [3]
The glomerular subendothelium is an ideal nesting spot for LPG-mutated lipoprotein to accumulate because mutated apoE has a higher affinity to both endothelial cells and the glomerular basement membrane.
“The glomerular subendothelium is an ideal nesting spot for LPG-mutated lipoprotein to accumulate since mutated apoE has a higher affinity to both endothelial cells and the glomerular basement membrane.”
From Lipoprotein Glomerulopathy, First Case Report from Canada (2022) · cites this paper as [3]
Patients with LPG often, but not always, have co-existent hypertriglyceridemia.
“Patients often, but not always, have co-existent hypertriglyceridemia.”
From Lipoprotein Glomerulopathy, First Case Report from Canada (2022) · cites this paper as [3]
Only lipid-lowering therapy has been verified efficiently to reduce proteinuria in LPG.
“Only lipid-lowering therapy has been verified efficiently to reduce proteinuria.13,14”
From The First Case of Lipoprotein Glomerulopathy in a Patient With Male Infertility (2026) · cites this paper as [13]
The main characteristics of LPG include proteinuria, hematuria, or both, elevated blood lipids, and increased serum ApoE.
“The main characteristics of LPG include proteinuria, hematuria, or both, elevated blood lipids, and increased serum ApoE.[7]”
From A boy and his mother with lipoprotein glomerulopathy: Two case reports and literature review (2025) · cites this paper as [7]
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The First Case of Lipoprotein Glomerulopathy in a Patient With Male Infertility
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- Authors
- Tsimihodimos, V., & Elisaf, M.
- Affiliations
- University of Ioannina (GR)
- Corresponding author
- Elisaf, Moses
- Venue
- Current Opinion in Lipidology
- Published
- 2011-08
- Volume
- 22
- Issue
- 4
- Pages
- 262-269
- ISSN
- 0957-9672 (ISSN-L)
- OpenAlex
- W4247849636
- Cited by
- 33
- References
- 48
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 4 · 2013: 6 · 2012: 2
- FWCI
- 0.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Lipidology (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 › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- lipoprotein glomerulopathy, type III hyperlipidemia, proteinuria, renal failure, lipoprotein metabolism, fibrates, LDL apheresis, immunoadsorption, lipid-lowering therapy, pathogenesis
- MeSH terms
- Animals, Apolipoproteins E, Humans, Hyperlipidemias, Kidney, Nephrosis, Proteinuria, Mutation, Missense
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