Circulating p-cresyl sulfate, non-hepatic alkaline phosphatase and risk of bone fracture events in chronic kidney disease-mineral bone disease

Jia Feng Chang, Chih Yu Hsieh, Jian Chiun Liou, Kuo Cheng Lu, Cai Mei Zheng, Mai Szu Wu, Shu Wei Chang, Ting Ming Wang, Chang Chin Wu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

2 Scopus citations


Patients with chronic kidney disease (CKD), especially those undergoing hemodialysis, are at a considerably high risk of bone fracture events. Experimental data indicate that uremic toxins intricately involved in bone-related proteins exert multi-faced toxicity on bone cells and tissues, leading to chronic kidney disease–mineral and bone disorder (CKD-MBD). Nonetheless, information regarding the association between p-cresyl sulfate (PCS), non-hepatic alkaline phosphatase (NHALP) and skeletal events remains elusive. We aim to explore the association between PCS, NHALP and risk of bone fracture (BF) in patients with hemodialysis. Plasma concentrations of PCS and NHALP were ascertained at study entry. Cox proportional hazard regression analyses were used to deter-mine unadjusted and adjusted hazard ratios (aHRs) of PCS for BF risk. In multivariable analysis, NHALP was associated with incremental risks of BFs [aHR: 1.06 (95% CI: 1.01–1.11)]. The association between the highest PCS tertile and BF risk remained robust [aHR: 2.87 (95% CI: 1.02–8.09)]. With respect to BF events, the interaction between NHALP and PCS was statistically significant (p value for the interaction term < 0.05). In addition to mineral dysregulation and hyperparathyroidism in hemodialysis patients, higher circulating levels of PCS and NHALP are intricately associated with incremental risk of BF events, indicating that a joint evaluation is more comprehensive than single marker. In light of the extremely high prevalence of CKD-MBD in the hemodialysis population, PCS may act as a pro-osteoporotic toxin and serve as a potential surrogate marker for skeletal events.

Original languageEnglish
Article number479
Issue number7
StatePublished - 07 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Alkaline phosphatase
  • Bone fracture
  • Chronic kidney disease–mineral and bone disorder
  • P-cresyl sulfate


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