Effect of uremic toxin-indoxyl sulfate on the skeletal system

Wen Chih Liu, Chia Chao Wu, Paik Seong Lim, Shiaw Wen Chien, Yi Chou Hou, Cai Mei Zheng, Jia Fwu Shyu, Yuh Feng Lin, Kuo Cheng Lu

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Chronic kidney disease-mineral bone disorders (CKD-MBD) exhibit abnormalities in the circulating mineral levels, vitamin D metabolism, and parathyroid function that contribute to the formation of a bone lesion. The uremic toxin, indoxyl sulfate (IS), accumulates in the blood in cases of renal failure and leads to bone loss. The bone and renal responses to the action of the parathyroid hormone (PTH) are progressively decreased in CKD in spite of increasing PTH levels, a condition commonly called PTH resistance. There is a high prevalence of low bone turnover or adynamic bone disease in the early stages of CKD. This could be due to the inhibition of bone turnover, such as in PTH resistance, reduced active vitamin D levels, diabetes, aluminum, and, increased IS. With an increase in IS, there is a decrease in the osteoblast Wnt/b-catenin signaling and increase in the expression of Wnt signaling inhibitors, such as sclerostin and Dickkopf-1 (DKK1). Thus, a majority of early CKD patients exhibit deterioration of bone quality owing to the action of IS, this scenario could be termed uremic osteoporosis. However, this mechanism is complicated and not fully understood. With progressive deterioration in the renal function, IS accumulates along with persistent PTH secretion, potentially leading to high-turnover bone disease because high serum PTH levels have the ability of overriding peripheral PTH resistance and other inhibitory factors of bone formation. Finally, it leads to deterioration in bone quantity with prominent bone resorption in end stage renal disease. Uremic toxins adsorbents may decelerate oxidative stress and improve bone health in CKD patients. This review article focuses on IS and bone loss in CKD patients.

Original languageEnglish
Pages (from-to)197-206
Number of pages10
JournalClinica Chimica Acta
Volume484
DOIs
Publication statusPublished - Sep 1 2018

Fingerprint

Indican
Parathyroid Hormone
Bone
Bone and Bones
Bone Remodeling
Bone Diseases
Osteogenesis
Vitamin D
Chronic Kidney Disease-Mineral and Bone Disorder
Kidney
Deterioration
Catenins
Bone Resorption
Aluminum
Osteoblasts
Osteoporosis
Chronic Kidney Failure
Renal Insufficiency
Minerals
Oxidative Stress

Keywords

  • Indoxyl sulfate
  • Low bone turnover
  • PTH resistance
  • Uremic osteoporosis
  • Uremic toxins adsorbent
  • Wnt inhibitors

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Liu, W. C., Wu, C. C., Lim, P. S., Chien, S. W., Hou, Y. C., Zheng, C. M., ... Lu, K. C. (2018). Effect of uremic toxin-indoxyl sulfate on the skeletal system. Clinica Chimica Acta, 484, 197-206. https://doi.org/10.1016/j.cca.2018.05.057

Effect of uremic toxin-indoxyl sulfate on the skeletal system. / Liu, Wen Chih; Wu, Chia Chao; Lim, Paik Seong; Chien, Shiaw Wen; Hou, Yi Chou; Zheng, Cai Mei; Shyu, Jia Fwu; Lin, Yuh Feng; Lu, Kuo Cheng.

In: Clinica Chimica Acta, Vol. 484, 01.09.2018, p. 197-206.

Research output: Contribution to journalReview article

Liu, WC, Wu, CC, Lim, PS, Chien, SW, Hou, YC, Zheng, CM, Shyu, JF, Lin, YF & Lu, KC 2018, 'Effect of uremic toxin-indoxyl sulfate on the skeletal system', Clinica Chimica Acta, vol. 484, pp. 197-206. https://doi.org/10.1016/j.cca.2018.05.057
Liu, Wen Chih ; Wu, Chia Chao ; Lim, Paik Seong ; Chien, Shiaw Wen ; Hou, Yi Chou ; Zheng, Cai Mei ; Shyu, Jia Fwu ; Lin, Yuh Feng ; Lu, Kuo Cheng. / Effect of uremic toxin-indoxyl sulfate on the skeletal system. In: Clinica Chimica Acta. 2018 ; Vol. 484. pp. 197-206.
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AU - Hou, Yi Chou

AU - Zheng, Cai Mei

AU - Shyu, Jia Fwu

AU - Lin, Yuh Feng

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N2 - Chronic kidney disease-mineral bone disorders (CKD-MBD) exhibit abnormalities in the circulating mineral levels, vitamin D metabolism, and parathyroid function that contribute to the formation of a bone lesion. The uremic toxin, indoxyl sulfate (IS), accumulates in the blood in cases of renal failure and leads to bone loss. The bone and renal responses to the action of the parathyroid hormone (PTH) are progressively decreased in CKD in spite of increasing PTH levels, a condition commonly called PTH resistance. There is a high prevalence of low bone turnover or adynamic bone disease in the early stages of CKD. This could be due to the inhibition of bone turnover, such as in PTH resistance, reduced active vitamin D levels, diabetes, aluminum, and, increased IS. With an increase in IS, there is a decrease in the osteoblast Wnt/b-catenin signaling and increase in the expression of Wnt signaling inhibitors, such as sclerostin and Dickkopf-1 (DKK1). Thus, a majority of early CKD patients exhibit deterioration of bone quality owing to the action of IS, this scenario could be termed uremic osteoporosis. However, this mechanism is complicated and not fully understood. With progressive deterioration in the renal function, IS accumulates along with persistent PTH secretion, potentially leading to high-turnover bone disease because high serum PTH levels have the ability of overriding peripheral PTH resistance and other inhibitory factors of bone formation. Finally, it leads to deterioration in bone quantity with prominent bone resorption in end stage renal disease. Uremic toxins adsorbents may decelerate oxidative stress and improve bone health in CKD patients. This review article focuses on IS and bone loss in CKD patients.

AB - Chronic kidney disease-mineral bone disorders (CKD-MBD) exhibit abnormalities in the circulating mineral levels, vitamin D metabolism, and parathyroid function that contribute to the formation of a bone lesion. The uremic toxin, indoxyl sulfate (IS), accumulates in the blood in cases of renal failure and leads to bone loss. The bone and renal responses to the action of the parathyroid hormone (PTH) are progressively decreased in CKD in spite of increasing PTH levels, a condition commonly called PTH resistance. There is a high prevalence of low bone turnover or adynamic bone disease in the early stages of CKD. This could be due to the inhibition of bone turnover, such as in PTH resistance, reduced active vitamin D levels, diabetes, aluminum, and, increased IS. With an increase in IS, there is a decrease in the osteoblast Wnt/b-catenin signaling and increase in the expression of Wnt signaling inhibitors, such as sclerostin and Dickkopf-1 (DKK1). Thus, a majority of early CKD patients exhibit deterioration of bone quality owing to the action of IS, this scenario could be termed uremic osteoporosis. However, this mechanism is complicated and not fully understood. With progressive deterioration in the renal function, IS accumulates along with persistent PTH secretion, potentially leading to high-turnover bone disease because high serum PTH levels have the ability of overriding peripheral PTH resistance and other inhibitory factors of bone formation. Finally, it leads to deterioration in bone quantity with prominent bone resorption in end stage renal disease. Uremic toxins adsorbents may decelerate oxidative stress and improve bone health in CKD patients. This review article focuses on IS and bone loss in CKD patients.

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