TY - JOUR

T1 - Circadian rhythms of mineral metabolism in chronic kidney disease-mineral bone disorder

AU - Egstrand, Søren

AU - Olgaard, Klaus

AU - Lewin, Ewa

PY - 2020

Y1 - 2020

N2 - Purpose of reviewThe circadian rhythms have a systemic impact on all aspects of physiology. Kidney diseases are associated with extremely high-cardiovascular mortality, related to chronic kidney disease-mineral bone disorder (CKD-MBD), involving bone, parathyroids and vascular calcification. Disruption of circadian rhythms may cause serious health problems, contributing to development of cardiovascular diseases, metabolic syndrome, cancer, organ fibrosis, osteopenia and aging. Evidence of disturbed circadian rhythms in CKD-MBD parameters and organs involved is emerging and will be discussed in this review.Recent findingsKidney injury induces unstable behavioral circadian rhythm. Potentially, uremic toxins may affect the master-pacemaker of circadian rhythm in hypothalamus. In CKD disturbances in the circadian rhythms of CKD-MBD plasma-parameters, activin A, fibroblast growth factor 23, parathyroid hormone, phosphate have been demonstrated. A molecular circadian clock is also expressed in peripheral tissues, involved in CKD-MBD; vasculature, parathyroids and bone. Expression of the core circadian clock genes in the different tissues is disrupted in CKD-MBD.SummaryDisturbed circadian rhythms is a novel feature of CKD-MBD. There is a need to establish which specific input determines the phase of the local molecular clock and to characterize its regulation and deregulation in tissues involved in CKD-MBD. Finally, it is important to establish what are the implications for treatment including the potential applications for chronotherapy.

AB - Purpose of reviewThe circadian rhythms have a systemic impact on all aspects of physiology. Kidney diseases are associated with extremely high-cardiovascular mortality, related to chronic kidney disease-mineral bone disorder (CKD-MBD), involving bone, parathyroids and vascular calcification. Disruption of circadian rhythms may cause serious health problems, contributing to development of cardiovascular diseases, metabolic syndrome, cancer, organ fibrosis, osteopenia and aging. Evidence of disturbed circadian rhythms in CKD-MBD parameters and organs involved is emerging and will be discussed in this review.Recent findingsKidney injury induces unstable behavioral circadian rhythm. Potentially, uremic toxins may affect the master-pacemaker of circadian rhythm in hypothalamus. In CKD disturbances in the circadian rhythms of CKD-MBD plasma-parameters, activin A, fibroblast growth factor 23, parathyroid hormone, phosphate have been demonstrated. A molecular circadian clock is also expressed in peripheral tissues, involved in CKD-MBD; vasculature, parathyroids and bone. Expression of the core circadian clock genes in the different tissues is disrupted in CKD-MBD.SummaryDisturbed circadian rhythms is a novel feature of CKD-MBD. There is a need to establish which specific input determines the phase of the local molecular clock and to characterize its regulation and deregulation in tissues involved in CKD-MBD. Finally, it is important to establish what are the implications for treatment including the potential applications for chronotherapy.

KW - activin A

KW - fibroblast growth factor 23

KW - klotho

KW - parathyroid

KW - renal osteodystrophy

KW - vascular calcification

U2 - 10.1097/MNH.0000000000000611

DO - 10.1097/MNH.0000000000000611

M3 - Review

C2 - 32452917

AN - SCOPUS:85085586117

VL - 29

SP - 367

EP - 377

JO - Current Opinion in Nephrology & Hypertension

JF - Current Opinion in Nephrology & Hypertension

SN - 1062-4821

IS - 4

ER -