Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis

Nakajima, Kichitaro; Yamaguchi, Keiichi; Noji, Masahiro; Aguirre, César; Ikenaka, Kensuke; Mochizuki, Hideki; Zhou, Lianjie; Ogi, Hirotsugu; Ito, Toru; Narita, Ichiei; Gejyo, Fumitake; Naiki, Hironobu; Yamamoto, Suguru; Goto, Yuji

doi:https://doi.org/10.1038/s41467-022-33247-3

Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis

Nakajima, Kichitaro; Yamaguchi, Keiichi; Noji, Masahiro et al.

Nature Communications, 2022, 13, 5689

Number of Access:1,561（2025-08-14 15:06 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93309

Link to primary information

File	Format	Terms of use	Size	Views	Date.Available	Description	information
NatCommun_13_1	pdf	None	2.26 MB	92	2023.12.15

Creative Commons : Attribution

Item Information

Output File Export EndNote Basic Export Mendeley

Title	Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis
Creator	NRID 1000020867337 1000020867337 ORCID 0000-0003-2644-741X 0000-0003-2644-741X researchmap permalink sonochem sonochem Scopus Author ID 57145904700 57145904700 CreatorName Nakajima, Kichitaro
	NRID 1000090432187 1000090432187 researchmap permalink read0105908 read0105908 Scopus Author ID 8731908100 8731908100 CreatorName Yamaguchi, Keiichi
	NRID 1000020882723 1000020882723 CreatorName Noji, Masahiro
	NRID 1000020865597 1000020865597 CreatorName Aguirre, César
	NRID 1000070774058 1000070774058 researchmap permalink kensukeikenaka kensukeikenaka Scopus Author ID 8588484300 8588484300 CreatorName Ikenaka, Kensuke
	NRID 1000090230044 1000090230044 ORCID 0000-0002-0874-7542 0000-0002-0874-7542 researchmap permalink read0207787 read0207787 Scopus Author ID 7202006099 7202006099 CreatorName Mochizuki, Hideki
	CreatorName Zhou, Lianjie
	NRID 1000090252626 1000090252626 researchmap permalink read0042771 read0042771 Scopus Author ID 35563683500 35563683500 CreatorName Ogi, Hirotsugu
	CreatorName Ito, Toru
	NRID 1000020272817 1000020272817 CreatorName Narita, Ichiei
	NRID 1000020126410 1000020126410 CreatorName Gejyo, Fumitake
	NRID 1000010227704 1000010227704 CreatorName Naiki, Hironobu
	NRID 1000070444156 1000070444156 CreatorName Yamamoto, Suguru
	NRID 1000040153770 1000040153770 CreatorName Goto, Yuji
Description	Nakajima K., Yamaguchi K., Noji M., et al. Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis. Nature Communications 13, 5689 (2022); https://doi.org/10.1038/s41467-022-33247-3.
Abstract	Dialysis-related amyloidosis (DRA), a serious complication among long-term hemodialysis patients, is caused by amyloid fibrils of β2-microglobulin (β2m). Although high serum β2m levels and a long dialysis vintage are the primary and secondary risk factors for the onset of DRA, respectively, patients with these do not always develop DRA, indicating that there are additional risk factors. To clarify these unknown factors, we investigate the effects of human sera on β2m amyloid fibril formation, revealing that sera markedly inhibit amyloid fibril formation. Results from over 100 sera indicate that, although the inhibitory effects of sera deteriorate in long-term dialysis patients, they are ameliorated by maintenance dialysis treatments in the short term. Serum albumin prevents amyloid fibril formation based on macromolecular crowding effects, and decreased serum albumin concentration in dialysis patients is a tertiary risk factor for the onset of DRA. We construct a theoretical model assuming cumulative effects of the three risk factors, suggesting the importance of monitoring temporary and accumulated risks to prevent the development of amyloidosis, which occurs based on supersaturation-limited amyloid fibril formation in a crowded milieu.
Publisher	Nature Research
Source Title	Nature Communications
Volume (Issue)	13
Page	5689
Date of Issued	2022-10-03
Language	English
Handle URL	https://hdl.handle.net/11094/93309
eISSN	20411723
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41467-022-33247-3
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Nature Communications. 2022, 13, p. 5689
DC.title	Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis
DC.creator	Nakajima, Kichitaro
	Yamaguchi, Keiichi
	Noji, Masahiro
	Aguirre, César
	Ikenaka, Kensuke
	Mochizuki, Hideki
	Zhou, Lianjie
	Ogi, Hirotsugu
	Ito, Toru
	Narita, Ichiei
	Gejyo, Fumitake
	Naiki, Hironobu
	Yamamoto, Suguru
	Goto, Yuji
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2022-10-03
DC.identifier	https://doi.org/10.1038/s41467-022-33247-3
DC.description	Nakajima K., Yamaguchi K., Noji M., et al. Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis. Nature Communications 13, 5689 (2022); https://doi.org/10.1038/s41467-022-33247-3.
DCTERMS.abstract	Dialysis-related amyloidosis (DRA), a serious complication among long-term hemodialysis patients, is caused by amyloid fibrils of β2-microglobulin (β2m). Although high serum β2m levels and a long dialysis vintage are the primary and secondary risk factors for the onset of DRA, respectively, patients with these do not always develop DRA, indicating that there are additional risk factors. To clarify these unknown factors, we investigate the effects of human sera on β2m amyloid fibril formation, revealing that sera markedly inhibit amyloid fibril formation. Results from over 100 sera indicate that, although the inhibitory effects of sera deteriorate in long-term dialysis patients, they are ameliorated by maintenance dialysis treatments in the short term. Serum albumin prevents amyloid fibril formation based on macromolecular crowding effects, and decreased serum albumin concentration in dialysis patients is a tertiary risk factor for the onset of DRA. We construct a theoretical model assuming cumulative effects of the three risk factors, suggesting the importance of monitoring temporary and accumulated risks to prevent the development of amyloidosis, which occurs based on supersaturation-limited amyloid fibril formation in a crowded milieu.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93309
citation_title	Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis
citation_author	Nakajima, Kichitaro
	Yamaguchi, Keiichi
	Noji, Masahiro
	Aguirre, César
	Ikenaka, Kensuke
	Mochizuki, Hideki
	Zhou, Lianjie
	Ogi, Hirotsugu
	Ito, Toru
	Narita, Ichiei
	Gejyo, Fumitake
	Naiki, Hironobu
	Yamamoto, Suguru
	Goto, Yuji
citation_publisher	Nature Research
citation_language	English
citation_date	2022-10-03
citation_journal_title	Nature Communications
citation_volume	13
citation_firstpage	5689
citation_doi	https://doi.org/10.1038/s41467-022-33247-3
citation_public_url	https://hdl.handle.net/11094/93309

Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis

Link to primary information

Item Information

Show details