Hereditary features, treatment, and prognosis of the lipoprotein glomerulopathy in patients with the APOE Kyoto mutation
Open accessAbstract
Lipoprotein glomerulopathy is a rare inherited renal disease, caused by mutation of the APOE gene, characterized by proteinuria and nephrotic syndrome with elevated serum apoE. Since its treatment and outcome are unknown, we retrospectively studied 35 patients within 31 unrelated Han families with biopsy-proven lipoprotein glomerulopathy residing in the same county in southwest China. DNA sequencing detected the APOE Kyoto mutation (p. Arg25Cys) in all patients and 28 asymptomatic relatives. All shared the same ɛ3 allele. The patients presented with proteinuria, higher total triglyceride, and serum apoE levels relative to non-carriers. The serum apoE and triglyceride levels of asymptomatic carriers were between those of the patients and non-carriers. Sixteen patients received fenofibrate treatment for over 12 months. Six reached complete remission (proteinuria under 0.3 g/day with stable serum creatinine) with intensive control of their lipid profile (normalized serum apoE and triglycerides under 100 mg/dl). Eight reached partial remission. At 3 years of follow-up, patients treated with fenofibrate had superior survival and stable renal function. Thus, fenofibrate can induce lipoprotein glomerulopathy remission and the fibrate effects depend on the degree of lipid control and baseline proteinuria. Moreover, normalization of serum apoE and triglycerides can be used to judge the efficacy of lipid-lowering treatment.
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Most LPG patients have been reported to present elevated plasma apoE levels, while normalization or reduction of apoE levels following various treatments results in remission or improvement of the disease.
“Most of the LPG patients have been reported to present elevated plasma apoE levels (5, 6, 23-25), while it has been observed that normalization or reduction of apoE levels following various treatments (e.g., lipid-lowering treatments with fenofibrate or protein A immunoadsorption) result in remission or improvement of the disease (24,25,47).”
From Thermodynamic destabilization and aggregation propensity as the mechanism behind the association of apoE3 mutants and lipoprotein glomerulopathy (2018) · cites this paper as [24]
Fibrate should be effective for LPG.
“which should be effective for LPG [10,11].”
From Lipoprotein glomerulopathy with a novel apolipoprotein E variant, APOE Kanto (Asp 151dup) (2024) · cites this paper as [11]
The authors previously observed clustering of APOE Kyoto-causing LPG in a Han population in China.
“We previously observed clustering of “APOE Kyoto causing LPG” in a Han population in China.”
From Identification of a founder haplotype of <i>APOE Kyoto</i> variant in lipoprotein glomerulopathy (2025) · cites this paper as [7]
Genetic drift and population-specific factors may influence the prevalence and clinical presentation of lipoprotein glomerulopathy.
“These variants exhibit distinct geographical distributions and founder effects, suggesting that genetic drift and population-specific factors may influence the prevalence and clinical presentation.[3,4]”
From Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy (2026) · cites this paper as [3]
APOE variants linked to lipoprotein glomerulopathy exhibit distinct geographical distributions and founder effects.
“These variants exhibit distinct geographical distributions and founder effects, suggesting that genetic drift and population-specific factors may influence the prevalence and clinical presentation.[3,4]”
From Clinical characteristics and APOE variant spectrum in Chinese patients with lipoprotein glomerulopathy (2026) · cites this paper as [3]
Many cases have showed that intensive lipid-lowering treatment including fibrate for under 100 mg/dL of serum triglyceride could significantly reduce proteinuria and achieve clinical remission.
“Many cases in our previous work and others have showed that intensive lipid-lowering treatment including fibrate for under 100 mg/dL of serum triglyceride could significantly reduce proteinuria and achieve clinical remission1, 13, 17, 21–23).”
From The Novel Apolipoprotein E Mutation ApoE Chengdu (c.518T＞C, p.L173P) in a Chinese Patient with Lipoprotein Glomerulopathy (2018) · cites this paper as [1]
LPG is a rare autosomal dominant renal disease with incomplete penetrance that has mainly been reported in eastern Asia.
“Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant renal disease with incomplete penetrance that has mainly been reported in eastern Asia1, 2).”
From The Novel Apolipoprotein E Mutation ApoE Chengdu (c.518T＞C, p.L173P) in a Chinese Patient with Lipoprotein Glomerulopathy (2018) · cites this paper as [1]
LPG patients carrying apoE Sendai may show a lipoprotein profile ranging from near normal to one that resembles type III hyperlipoproteinemia.
“LPG patients carrying apoE Sendai may show a lipoprotein profi le ranging from near normal to one that resembles type III hyperlipoproteinemia (24)(25)(26).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [26]
LPG patients carrying apoE Sendai have higher apoE and cholesterol levels compared with asymptomatic apoE Sendai carriers.
“LPG patients carrying apoE Sendai have higher apoE and cholesterol levels compared with asymptomatic apoE Sendai carriers ( 26 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [26]
LPG patients present elevated apoE serum levels and often an abnormal lipid profile compared with control subjects.
“LPG patients present elevated apoE serum levels and often an abnormal lipid profi le compared with control subjects (24)(25)(26).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [26]
Fibrates are currently the mainstay of treatment for LPG, even for LPG patients who do not have dyslipidemia.
“Fibrates are currently the mainstay of treatment for LPG, even for LPG patients who do not have dyslipidemia.”
From Lipoprotein Glomerulopathy, First Case Report from Canada (2022) · cites this paper as [34]
One study of 35 LPG patients showed that patients who received fibrate therapy for at least 12 months had 93.7% renal survival versus only 30% renal survival after 3 years in those that did not receive a fibrate.
“One study of 35 LPG patients showed that patients who received fibrate therapy for at least 12 months had 93.7% renal survival versus only 30% renal survival after 3 years in those that did not receive a fibrate.34”
From Lipoprotein Glomerulopathy, First Case Report from Canada (2022) · cites this paper as [34]
Compared with the control group, the fibrates treatment group has significantly higher survival rate and kidney survival rate during the 3-year follow-up period.
“Compared with the control group, the fibrates treatment group has significantly higher survival rate and kidney survival rate during the 3-year follow-up period.[35]”
From A boy and his mother with lipoprotein glomerulopathy: Two case reports and literature review (2025) · cites this paper as [35]
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- Authors
- Hu, Z., Huang, S., Wu, Y., Liu, Y., Liu, X., Su, D., Tao, Y., Fu, P., Zhang, X., Peng, Z., Zhang, S., & Yang, Y.
- Affiliations
- Sichuan University (CN)
- Kanazawa University (JP)
- Corresponding author
- Hu, Zhangxue
- Zhang, Xiuhui
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2014
- Volume
- 85
- Issue
- 2
- Pages
- 416-424
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W1992904513
- Cited by
- 60
- References
- 12
- Citations by year
- 2026: 8 · 2025: 4 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 8 · 2020: 2 · 2019: 5 · 2018: 5 · 2017: 2 · 2016: 5 · 2015: 2 · 2014: 6 · 2013: 1
- FWCI
- 3.53
- 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 › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- lipoprotein glomerulopathy, APOE ε3 allele, hereditary nephrotic syndrome, proteinuria, triglycerides, fenofibrate, lipid-lowering therapy, remission, prognosis, Han Chinese family, familial renal disease
- MeSH terms
- Adolescent, Adult, Aged, Hypolipidemic Agents, Biopsy, China, Creatinine, DNA Mutational Analysis, Female, Humans, Kidney, Kidney Diseases, Kidney Failure, Chronic, Male, Middle Aged, Mutation, Pedigree, Phenotype, Fenofibrate, Proteinuria, Remission Induction, Risk Factors, Time Factors, Triglycerides, Biomarkers, Case-Control Studies, Treatment Outcome, Disease Progression, Genetic Predisposition to Disease, Heredity, Kaplan-Meier Estimate, Apolipoprotein E2, Young Adult
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