The Role of Gut Dysbiosis in the Bone-Vascular Axis in Chronic Kidney Disease

Pieter Evenepoel, Sander Dejongh, Kristin Verbeke, Bjorn Meijers, Pieter Evenepoel, Sander Dejongh, Kristin Verbeke, Bjorn Meijers

Abstract

Patients with chronic kidney disease (CKD) are at increased risk of bone mineral density loss and vascular calcification. Bone demineralization and vascular mineralization often concur in CKD, similar to what observed in the general population. This contradictory association is commonly referred to as the 'calcification paradox' or the bone-vascular axis. Mounting evidence indicates that CKD-associated gut dysbiosis may be involved in the pathogenesis of the bone-vascular axis. A disrupted intestinal barrier function, a metabolic shift from a predominant saccharolytic to a proteolytic fermentation pattern, and a decreased generation of vitamin K may, alone or in concert, drive a vascular and skeletal pathobiology in CKD patients. A better understanding of the role of gut dysbiosis in the bone-vascular axis may open avenues for novel therapeutics, including nutriceuticals.

Keywords: CKD; bone; gut; vascular calcification.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The kidney–gut–bone–vascular axis. Chronic kidney disease is associated with gut dysbiosis, characterized by a metabolic shift towards a predominantly proteolytic fermentation pattern and a leaky gut. Gut dysbiosis may induce bone loss and vascular calcification and as such may play a pathogenic role in the bone–vascular axis in CKD. Underlying pathophysiological mechanisms include increased exposure to protein fermentation metabolites (such as p-cresyl sulfate (PCS) and indoxyl sulfate (IndS)), a leaky gut contributing to inflammation, and deficiency of vitamin K and short-chain fatty acids (SCFAs).

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Source: PubMed

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