Tags

Type your tag names separated by a space and hit enter

Molecular mechanisms underlying uremic toxin-related systemic disorders in chronic kidney disease: focused on β2-microglobulin-related amyloidosis and indoxyl sulfate-induced atherosclerosis-Oshima Award Address 2016.
Clin Exp Nephrol. 2019 Feb; 23(2):151-157.CE

Abstract

Uremic toxins are linked to chronic kidney disease (CKD)-related systemic diseases. β2-Microglobulin (β2-m), a water-soluble, middle-sized molecule, is associated with mortality and dialysis-related amyloidosis (DRA). DRA occurs in long-term dialysis patients, with β2-m amyloid deposited mainly in osteoarticular tissues. We investigated a model of β2-m amyloid fibril extension at neutral pH in the presence of trifluoroethanol or sodium dodecyl sulfate. Using this model, some biological molecules, including glycosaminoglycans and lysophospholipids, were found to be chaperones for β2-m amyloid fibril extension. Several protein-bound solutes, such as indoxyl sulfate (IS) and p-cresyl sulfate, are independent risk factors for cardiovascular disease in CKD patients, especially those undergoing dialysis. We investigated kidney injury-induced acceleration of atherosclerosis in association with macrophage phenotypic change to a proinflammatory state as well as increased IS deposition in lesions in an animal model. IS directly induced macrophage inflammation and impaired cholesterol efflux to high-density lipoprotein (HDL) in vitro. In addition, a clinical study showed that HDL isolated from CKD patients induced proinflammatory reactions and impaired cholesterol efflux to macrophages. These findings suggest that protein-bound solutes, including IS, will induce dysfunction of both macrophages and HDL in atherosclerotic lesions. To remove uremic toxins efficiently, we demonstrated the potential efficacy of oral charcoal adsorbent and hexadecyl-immobilized cellulose beads in hemodialysis patients. These findings suggest that uremic toxins induce various CKD-related systemic disorders, and further therapeutic strategies will be needed to reduce uremic toxins enough and improve life expectancy in CKD patients.

Authors+Show Affiliations

Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan. yamamots@med.niigata-u.ac.jp.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

29869756

Citation

Yamamoto, Suguru. "Molecular Mechanisms Underlying Uremic Toxin-related Systemic Disorders in Chronic Kidney Disease: Focused On Β2-microglobulin-related Amyloidosis and Indoxyl Sulfate-induced atherosclerosis-Oshima Award Address 2016." Clinical and Experimental Nephrology, vol. 23, no. 2, 2019, pp. 151-157.
Yamamoto S. Molecular mechanisms underlying uremic toxin-related systemic disorders in chronic kidney disease: focused on β2-microglobulin-related amyloidosis and indoxyl sulfate-induced atherosclerosis-Oshima Award Address 2016. Clin Exp Nephrol. 2019;23(2):151-157.
Yamamoto, S. (2019). Molecular mechanisms underlying uremic toxin-related systemic disorders in chronic kidney disease: focused on β2-microglobulin-related amyloidosis and indoxyl sulfate-induced atherosclerosis-Oshima Award Address 2016. Clinical and Experimental Nephrology, 23(2), 151-157. https://doi.org/10.1007/s10157-018-1588-9
Yamamoto S. Molecular Mechanisms Underlying Uremic Toxin-related Systemic Disorders in Chronic Kidney Disease: Focused On Β2-microglobulin-related Amyloidosis and Indoxyl Sulfate-induced atherosclerosis-Oshima Award Address 2016. Clin Exp Nephrol. 2019;23(2):151-157. PubMed PMID: 29869756.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular mechanisms underlying uremic toxin-related systemic disorders in chronic kidney disease: focused on β2-microglobulin-related amyloidosis and indoxyl sulfate-induced atherosclerosis-Oshima Award Address 2016. A1 - Yamamoto,Suguru, Y1 - 2018/06/05/ PY - 2018/02/11/received PY - 2018/05/07/accepted PY - 2018/6/6/pubmed PY - 2019/6/18/medline PY - 2018/6/6/entrez KW - Atherosclerosis KW - Dialysis-related amyloidosis KW - Indoxyl sulfate KW - Macrophages KW - Uremic toxins KW - β2-Microglobulin SP - 151 EP - 157 JF - Clinical and experimental nephrology JO - Clin Exp Nephrol VL - 23 IS - 2 N2 - Uremic toxins are linked to chronic kidney disease (CKD)-related systemic diseases. β2-Microglobulin (β2-m), a water-soluble, middle-sized molecule, is associated with mortality and dialysis-related amyloidosis (DRA). DRA occurs in long-term dialysis patients, with β2-m amyloid deposited mainly in osteoarticular tissues. We investigated a model of β2-m amyloid fibril extension at neutral pH in the presence of trifluoroethanol or sodium dodecyl sulfate. Using this model, some biological molecules, including glycosaminoglycans and lysophospholipids, were found to be chaperones for β2-m amyloid fibril extension. Several protein-bound solutes, such as indoxyl sulfate (IS) and p-cresyl sulfate, are independent risk factors for cardiovascular disease in CKD patients, especially those undergoing dialysis. We investigated kidney injury-induced acceleration of atherosclerosis in association with macrophage phenotypic change to a proinflammatory state as well as increased IS deposition in lesions in an animal model. IS directly induced macrophage inflammation and impaired cholesterol efflux to high-density lipoprotein (HDL) in vitro. In addition, a clinical study showed that HDL isolated from CKD patients induced proinflammatory reactions and impaired cholesterol efflux to macrophages. These findings suggest that protein-bound solutes, including IS, will induce dysfunction of both macrophages and HDL in atherosclerotic lesions. To remove uremic toxins efficiently, we demonstrated the potential efficacy of oral charcoal adsorbent and hexadecyl-immobilized cellulose beads in hemodialysis patients. These findings suggest that uremic toxins induce various CKD-related systemic disorders, and further therapeutic strategies will be needed to reduce uremic toxins enough and improve life expectancy in CKD patients. SN - 1437-7799 UR - https://www.unboundmedicine.com/medline/citation/29869756/Molecular_mechanisms_underlying_uremic_toxin_related_systemic_disorders_in_chronic_kidney_disease:_focused_on_β2_microglobulin_related_amyloidosis_and_indoxyl_sulfate_induced_atherosclerosis_Oshima_Award_Address_2016_ L2 - https://dx.doi.org/10.1007/s10157-018-1588-9 DB - PRIME DP - Unbound Medicine ER -