Disappearance of intraglomerular lipoprotein thrombi and marked improvement of nephrotic syndrome by bezafibrate treatment in a patient with lipoprotein glomerulopathy

Arai, Takeshi; Yamashita, Shizuya; Yamane, Mitsukazu; Manabe, Noriko; Matsuzaki, Toshiyuki; Kiriyama, Kazuo; Kanayama, Yoshio; Himeno, Seiichi; Matsuzawa, Yuji

doi:10.1016/s0021-9150(03)00194-1

Cited by 43Renal Diseases and GlomerulopathiesLipid metabolism and disordersChronic Kidney Disease and Diabetes

Disappearance of intraglomerular lipoprotein thrombi and marked improvement of nephrotic syndrome by bezafibrate treatment in a patient with lipoprotein glomerulopathy

Arai, Takeshi, Yamashita, Shizuya, Yamane, Mitsukazu, Manabe, Noriko, Matsuzaki, Toshiyuki, Kiriyama, Kazuo, Kanayama, Yoshio, Himeno, Seiichi +1 more·2003·Atherosclerosis

DOI 10.1016/s0021-9150(03)00194-1

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Abstract

Lipoprotein glomerulopathy (LPG) is a hereditary disorder characterized by intraglomerular lipoprotein thrombi and increased serum apolipoprotein (apo) E. Patients with LPG usually manifest with nephrotic syndrome, and some progress to renal failure; however, no effective therapeutic regimen has been established for this disease. We experienced a patient with LPG for whom bezafibrate treatment was very effective. This 30-year-old Japanese woman had nephrotic syndrome and type III hyperlipoproteinemia. Renal biopsy showed markedly dilated capillary lumina containing massive lipoprotein thrombi. Plasma apo E concentration was elevated to twice that of normal controls. She was proved to be a heterozygote of apo E2 Kyoto (Arg25Cys). After 2 years treatment with bezafibrate (400 mg/day), her plasma albumin gradually increased from 2.1 to 4.0 mg/dl, and intraglomerular lipoprotein thrombi disappeared almost completely. Bezafibrate decreased plasma apo E and dramatically increased high density lipoprotein (HDL)-cholesterol. The decrease in apo E was observed mainly in the pre-beta-fraction, not in the alpha fraction. Lipidological analyses of our patient suggest that the origin her lipoprotein thrombi may be mainly from pre-beta-lipoproteins and that HDL might be involved in resolving lipoprotein thrombi. Our case suggests that administration of fibrates such as bezafibrate may be a novel therapeutic strategy for resolving intraglomerular thrombi and improving nephrotic syndrome in…

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Lipid-lowering treatment has been shown to alleviate proteinuria and even reverse renal capillary lipoprotein thrombi in LPG.
“while lipid-lowering treatment has been shown to alleviate proteinuria and even reverses renal capillary lipoprotein thrombi in LPG [20].”
From A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation (2024) · cites this paper as [20]
Fibrates and ACEI/ARB may be effective for LPG remission.
“Though no effective treatment has been established, fibrates and ACEI/ARB may be effective for LPG remission (Arai et al., 2003; Ieiri, Hotta, & Taguma, 2003; Matsunaga et al., 2009).”
From Clinical and genetic analysis of lipoprotein glomerulopathy patients caused by APOE mutations (2020) · cites this paper as Arai et al., 2003
Normolipidemic or mildly hyperlipidemic LPG patients also benefit from fibrate treatment.
“Notably, normolipidemic or mildly hyperlipidemic LPG patients also benefit from fibrate treatment17, 22, 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 [23]
Worldwide, only 22 cases of LPG including this case have reported the results of more than one native kidney biopsy.
“Worldwide, only 22 cases of LPG including this case have reported the results of more than one native kidney biopsy.14,15,29,32,44–49”
From Lipoprotein Glomerulopathy, First Case Report from Canada (2022) · cites this paper as [45]
Previous case reports found combined treatment with glucocorticoids and immunosuppressants ineffective; intensified treatment with lipid-lowering drugs including fibrates provided clinical and histological relief, with serum cholesterol, triglycerides, and ApoE decreased, and consecutive renal biopsies demonstrated complete disappearance of lipoprotein thrombi.
“Previous case reports that found combined treatment with glucocorticoids and immunosuppressants ineffective used intensified treatment with lipid-lowering drugs (including fibrates) to provide clinical and histological relief for patients. In those cases, serum cholesterol, triglycerides, and ApoE decreased, and consecutive renal biopsies demonstrated complete disappearance of lipoprotein thrombi.”
From A boy and his mother with lipoprotein glomerulopathy: Two case reports and literature review (2025) · cites this paper as [33]

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Authors: Arai, T., Yamashita, S., Yamane, M., Manabe, N., Matsuzaki, T., Kiriyama, K., Kanayama, Y., Himeno, S., & Matsuzawa, Y.
Affiliations: Ashiya Municipal Hospital (JP)
The University of Osaka (JP)
Kawasaki Hospital (JP)
Corresponding author: Yamashita, Shizuya
ORCID: Arai, Takeshi
Yamashita, Shizuya
Venue: Atherosclerosis
Publisher: Elsevier BV
Published: 2003-08
Volume: 169
Issue: 2
Pages: 293-299
ISSN: 0021-9150 (ISSN-L)
DOI: 10.1016/s0021-9150(03)00194-1
OpenAlex: W2040410655
Cited by: 43
References: 26
Citations by year: 2026: 1 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 2 · 2016: 2 · 2014: 2 · 2013: 3 · 2012: 2
FWCI: 1.05
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Atherosclerosis (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, nephrotic syndrome, bezafibrate, fibrates, apolipoprotein E, type III hyperlipoproteinemia, HDL cholesterol, pre-beta-lipoprotein, hereditary kidney disease
MeSH terms: Adult, Hypolipidemic Agents, Apolipoproteins E, Bezafibrate, Female, Humans, Kidney Diseases, Kidney Glomerulus, Lipoproteins, Lipoproteins, HDL, Cholesterol, HDL, Nephrotic Syndrome, Thrombosis, Apolipoprotein E2, High-Density Lipoproteins, Pre-beta

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Disappearance of intraglomerular lipoprotein thrombi and marked improvement of nephrotic syndrome by bezafibrate treatment in a patient with lipoprotein glomerulopathy

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