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Elevated Levels of Peripheral Kynurenine Decrease Bone Strength in Rats with Chronic Kidney Disease

Overview of attention for article published in Frontiers in Physiology, October 2017
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Title
Elevated Levels of Peripheral Kynurenine Decrease Bone Strength in Rats with Chronic Kidney Disease
Published in
Frontiers in Physiology, October 2017
DOI 10.3389/fphys.2017.00836
Pubmed ID
Authors

Bartlomiej Kalaska, Krystyna Pawlak, Tomasz Domaniewski, Ewa Oksztulska-Kolanek, Beata Znorko, Alicja Roszczenko, Joanna Rogalska, Malgorzata M. Brzoska, Pawel Lipowicz, Michal Doroszko, Anna Pryczynicz, Dariusz Pawlak

Abstract

The diagnosis and treatment of bone disorders in patients with chronic kidney disease (CKD) represent a clinical challenge. CKD leads to mineral and bone complications starting early in the course of renal failure. Recently, we have observed the positive relationship between intensified central kynurenine turnover and bone strength in rats with subtotal 5/6 nephrectomy (5/6 Nx)-induced CKD. The aim of the present study was to determine the association between peripheral kynurenine pathway metabolites and bone strength in rats with 5/6 Nx-induced CKD. The animals were sacrificed 1 and 3 months after 5/6 Nx or sham operation. Nephrectomized rats presented higher concentrations of serum creatinine, urea nitrogen, and parathyroid hormone both 1 and 3 months after nephrectomy. These animals revealed higher concentrations of kynurenine and 3-hydroxykynurenine in the serum and higher gene expression of aryl hydrocarbon receptor (AhR) as a physiological receptor for kynurenine and AhR-dependent cytochrome in the bone tissue. Furthermore, nephrectomy significantly increased the number of osteoclasts in the bone without affecting their resorptive activity measured in serum. These changes were particularly evident in rats 1 month after 5/6 Nx. The main bone biomechanical parameters of the tibia were unchanged between nephrectomized and sham-operated rats but were significantly increased in older compared to younger animals. A similar trend was observed for geometrical parameters measured with calipers, bone mineral density based on Archimedes' method and image of bone microarchitecture obtained from micro-computed tomography analyses of tibial cortical bone. In nephrectomized animals, peripheral kynurenine levels correlated negatively with the main parameters of bone biomechanics, bone geometry, and bone mineral density values. In conclusion, our data suggest that CKD-induced elevated levels of peripheral kynurenine cause pathological changes in bone structure via AhR pathway. This finding opens new opportunities for the treatment/prevention of osteoporosis in CKD.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 19 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 4 21%
Student > Master 4 21%
Student > Bachelor 2 11%
Student > Doctoral Student 1 5%
Other 1 5%
Other 2 11%
Unknown 5 26%
Readers by discipline Count As %
Agricultural and Biological Sciences 3 16%
Medicine and Dentistry 3 16%
Pharmacology, Toxicology and Pharmaceutical Science 1 5%
Immunology and Microbiology 1 5%
Psychology 1 5%
Other 3 16%
Unknown 7 37%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 November 2017.
All research outputs
#20,451,228
of 23,007,053 outputs
Outputs from Frontiers in Physiology
#9,477
of 13,760 outputs
Outputs of similar age
#286,637
of 328,927 outputs
Outputs of similar age from Frontiers in Physiology
#237
of 347 outputs
Altmetric has tracked 23,007,053 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 13,760 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 347 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.