PIVKA-II but not dp-ucMGP is associated with aortic calcification in chronic kidney disease

Abstract Background Patients with chronic kidney disease (CKD) are susceptible to vascular calcification and vitamin K deficiency. Matrix gla protein (MGP) is a potent inhibitor of calcification requiring vitamin K for activation. Inactive MGP, i.e. dephosphorylated uncarboxylated MGP (dp-ucMGP), is...

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Main Authors: Jakob Nyvad, Kent Lodberg Christensen, Gratien Andersen, Mark Reinhard, Bjarne Linde Nørgaard, Jonna Skov Madsen, Sebastian Nielsen, Martin Bjergskov Thomsen, Jesper Møller Jensen, Christian Daugaard Peters, Niels Henrik Buus
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Language:English
Published: BMC 2024-11-01
Series:BMC Nephrology
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Online Access:https://doi.org/10.1186/s12882-024-03876-5
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author Jakob Nyvad
Kent Lodberg Christensen
Gratien Andersen
Mark Reinhard
Bjarne Linde Nørgaard
Jonna Skov Madsen
Sebastian Nielsen
Martin Bjergskov Thomsen
Jesper Møller Jensen
Christian Daugaard Peters
Niels Henrik Buus
author_facet Jakob Nyvad
Kent Lodberg Christensen
Gratien Andersen
Mark Reinhard
Bjarne Linde Nørgaard
Jonna Skov Madsen
Sebastian Nielsen
Martin Bjergskov Thomsen
Jesper Møller Jensen
Christian Daugaard Peters
Niels Henrik Buus
author_sort Jakob Nyvad
collection DOAJ
description Abstract Background Patients with chronic kidney disease (CKD) are susceptible to vascular calcification and vitamin K deficiency. Matrix gla protein (MGP) is a potent inhibitor of calcification requiring vitamin K for activation. Inactive MGP, i.e. dephosphorylated uncarboxylated MGP (dp-ucMGP), is frequently elevated in CKD along with protein induced by vitamin K absence (PIVKA-II). We investigated whether dp-ucMGP and PIVKA-II are useful markers of aortic calcification in CKD. Methods Patients with normal or reduced kidney function underwent a non-contrast computed tomography scan of the entire aorta with subsequent blinded standard calcification scoring of the aortic wall ad modum Agatston. Blood samples were analyzed for plasma concentrations of dp-ucMGP and PIVKA-II. Results 141 patients (104 with CKD stage 3–5) were included. In patients with/without CKD median (interquartile range) were dp-ucMGP 543 (503–744)/1078 (835–1682) pmol/l (P < 0.01); PIVKA-II 19.3 (16.3–23.5)/21.8 (17.2–36.8) ng/ml (P = 0.33) and aortic Agatston scores 1644 (729–4138)/7172 (2834–15360) (P < 0.01). Agatston score was positively associated with PIVKA-II (β = 0.71, P = 0.014, r2 = 0.04) and tended to be so with dp-ucMGP (β = 0.44, P = 0.08, r2 = 0.02). Age, estimated glomerular filtration rate (eGFR) and smoking status were also associated with Agatston score and remained so, along with PIVKA-II, when adjusted for potential confounders. However, the association between age and aortic Agatston score was stronger than for PIVKA-II, eGFR and smoking-status. Conclusion Vitamin K deficiency, as estimated through PIVKA-II, but not dp-ucMGP, is weakly associated with aortic Agatston score. Yet, as markers of aortic calcification, both were outperformed substantially by age, and neither surpassed smoking nor eGFR. ClinicalTrials.gov identifier NCT04114695.
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spelling doaj-art-1d144fd7b74f4d0ca3196ff22a8840c62024-12-01T12:13:52ZengBMCBMC Nephrology1471-23692024-11-0125111010.1186/s12882-024-03876-5PIVKA-II but not dp-ucMGP is associated with aortic calcification in chronic kidney diseaseJakob Nyvad0Kent Lodberg Christensen1Gratien Andersen2Mark Reinhard3Bjarne Linde Nørgaard4Jonna Skov Madsen5Sebastian Nielsen6Martin Bjergskov Thomsen7Jesper Møller Jensen8Christian Daugaard Peters9Niels Henrik Buus10Department of Renal Medicine, Aarhus University HospitalDepartment of Cardiology, Aarhus University HospitalDepartment of Radiology, Aarhus University HospitalDepartment of Renal Medicine, Aarhus University HospitalDepartment of Cardiology, Aarhus University HospitalDepartment of Biochemistry and Immunology, Lillebaelt Hospital, University Hospital of Southern DenmarkDepartment of Renal Medicine, Aarhus University HospitalDepartment of Renal Medicine, Aarhus University HospitalDepartment of Cardiology, Aarhus University HospitalDepartment of Renal Medicine, Aarhus University HospitalDepartment of Renal Medicine, Aarhus University HospitalAbstract Background Patients with chronic kidney disease (CKD) are susceptible to vascular calcification and vitamin K deficiency. Matrix gla protein (MGP) is a potent inhibitor of calcification requiring vitamin K for activation. Inactive MGP, i.e. dephosphorylated uncarboxylated MGP (dp-ucMGP), is frequently elevated in CKD along with protein induced by vitamin K absence (PIVKA-II). We investigated whether dp-ucMGP and PIVKA-II are useful markers of aortic calcification in CKD. Methods Patients with normal or reduced kidney function underwent a non-contrast computed tomography scan of the entire aorta with subsequent blinded standard calcification scoring of the aortic wall ad modum Agatston. Blood samples were analyzed for plasma concentrations of dp-ucMGP and PIVKA-II. Results 141 patients (104 with CKD stage 3–5) were included. In patients with/without CKD median (interquartile range) were dp-ucMGP 543 (503–744)/1078 (835–1682) pmol/l (P < 0.01); PIVKA-II 19.3 (16.3–23.5)/21.8 (17.2–36.8) ng/ml (P = 0.33) and aortic Agatston scores 1644 (729–4138)/7172 (2834–15360) (P < 0.01). Agatston score was positively associated with PIVKA-II (β = 0.71, P = 0.014, r2 = 0.04) and tended to be so with dp-ucMGP (β = 0.44, P = 0.08, r2 = 0.02). Age, estimated glomerular filtration rate (eGFR) and smoking status were also associated with Agatston score and remained so, along with PIVKA-II, when adjusted for potential confounders. However, the association between age and aortic Agatston score was stronger than for PIVKA-II, eGFR and smoking-status. Conclusion Vitamin K deficiency, as estimated through PIVKA-II, but not dp-ucMGP, is weakly associated with aortic Agatston score. Yet, as markers of aortic calcification, both were outperformed substantially by age, and neither surpassed smoking nor eGFR. ClinicalTrials.gov identifier NCT04114695.https://doi.org/10.1186/s12882-024-03876-5AtherosclerosisChronic kidney diseaseVitamin K dependent proteinsAortaCalcificationAgeing
spellingShingle Jakob Nyvad
Kent Lodberg Christensen
Gratien Andersen
Mark Reinhard
Bjarne Linde Nørgaard
Jonna Skov Madsen
Sebastian Nielsen
Martin Bjergskov Thomsen
Jesper Møller Jensen
Christian Daugaard Peters
Niels Henrik Buus
PIVKA-II but not dp-ucMGP is associated with aortic calcification in chronic kidney disease
BMC Nephrology
Atherosclerosis
Chronic kidney disease
Vitamin K dependent proteins
Aorta
Calcification
Ageing
title PIVKA-II but not dp-ucMGP is associated with aortic calcification in chronic kidney disease
title_full PIVKA-II but not dp-ucMGP is associated with aortic calcification in chronic kidney disease
title_fullStr PIVKA-II but not dp-ucMGP is associated with aortic calcification in chronic kidney disease
title_full_unstemmed PIVKA-II but not dp-ucMGP is associated with aortic calcification in chronic kidney disease
title_short PIVKA-II but not dp-ucMGP is associated with aortic calcification in chronic kidney disease
title_sort pivka ii but not dp ucmgp is associated with aortic calcification in chronic kidney disease
topic Atherosclerosis
Chronic kidney disease
Vitamin K dependent proteins
Aorta
Calcification
Ageing
url https://doi.org/10.1186/s12882-024-03876-5
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