Skip to main content
Erschienen in: Journal of Nephrology 4/2019

01.08.2019 | Original Article

Osteocalcin (bone GLA protein) levels, vascular calcifications, vertebral fractures and mortality in hemodialysis patients with diabetes mellitus

verfasst von: Maria Fusaro, Maurizio Gallieni, Andrea Aghi, Maria Antonietta Rizzo, Giorgio Iervasi, Thomas L. Nickolas, Fabrizio Fabris, Maria Cristina Mereu, Sandro Giannini, Stefania Sella, Andrea Giusti, Annalisa Pitino, Graziella D’Arrigo, Maurizio Rossini, Davide Gatti, Maura Ravera, Luca Di Lullo, Antonio Bellasi, Giuliano Brunori, Antonio Piccoli, Giovanni Tripepi, Mario Plebani

Erschienen in: Journal of Nephrology | Ausgabe 4/2019

Einloggen, um Zugang zu erhalten

Abstract

Background and aims

Diabetes mellitus is recognized as one of the major causes of end stage kidney disease. Bone Gla protein (BGP) is a vitamin K-dependent protein involved in bone mineralization and vascular calcifications (VC). Our goal was to characterize BGP and undercarboxylated BGP (ucBGP) in DM patients on HD, compared to HD patients without DM, and their association with vascular and bone disease.

Methods

387 HD patients from 18 dialysis centers in Italy. Associations of DM, levels of BGP, vitamin D and VC were evaluated. Time-to-event analysis for all-cause mortality was performed by the Kaplan–Meier.

Results

Patients with DM had lower levels of total BGP (139.00 vs. 202.50 mcg/L, p < 0.001), 25(OH)D (23.4 vs. 30.2 ng/ml, p < 0.001), and ucBGP (9.24 vs. 11.32 mcg/L, p = 0.022). In regression models, the geometric means of total BGP and ucBGP were 19% (p = 0.009) and 26% (p = 0.034) lower in diabetic patients. In univariate Cox regression analysis, DM patients had a higher risk of all-cause mortality (HR:1.83, 95% CI 1.13–2.96, p = 0.014). Adjustment for confounders confirmed the significant DM-mortality link. We included VC and warfarin into the Cox model, the DM-mortality link was no longer significant, suggesting a role of these risk factors as causal mediators leading to increased mortality in dialysis patients.

Conclusions

HD patients have an increased mortality risk associated with DM. Furthermore, we found an association between DM and decreased BGP levels. Although our study does not support the notion that BGP levels act as mediator in the DM-mortality link, to our knowledge this is the first study in HD patients suggesting a potential protective role of BGP in the bone, endocrine and vascular pathway.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Bergman A, Qureshi AR, Haarhaus M et al (2017) Total and bone-specific alkaline phosphatase are associated with bone mineral density over time in end-stage renal disease patients starting dialysis. J Nephrol 30(2):255–262CrossRefPubMed Bergman A, Qureshi AR, Haarhaus M et al (2017) Total and bone-specific alkaline phosphatase are associated with bone mineral density over time in end-stage renal disease patients starting dialysis. J Nephrol 30(2):255–262CrossRefPubMed
2.
Zurück zum Zitat Torres PAU, Cohen-Solal M (2017) Evaluation of fracture risk in chronic kidney disease. J Nephrol 30(5):653–661CrossRefPubMed Torres PAU, Cohen-Solal M (2017) Evaluation of fracture risk in chronic kidney disease. J Nephrol 30(5):653–661CrossRefPubMed
3.
Zurück zum Zitat Neve A, Corrado A, Cantatore FP (2013) Osteocalcin: skeletal and extraskeletal effects. J Cell Physiol 228:1149–1153CrossRefPubMed Neve A, Corrado A, Cantatore FP (2013) Osteocalcin: skeletal and extraskeletal effects. J Cell Physiol 228:1149–1153CrossRefPubMed
4.
Zurück zum Zitat Bacchetta J, Boutroy S, Guebre-Egziabher F et al (2009) The relationship between adipokines, osteocalcin and bone quality in chronic kidney disease. Nephrol Dial Transpl 24:3120–3125CrossRef Bacchetta J, Boutroy S, Guebre-Egziabher F et al (2009) The relationship between adipokines, osteocalcin and bone quality in chronic kidney disease. Nephrol Dial Transpl 24:3120–3125CrossRef
5.
Zurück zum Zitat Fusaro M, Gallieni M, Noale M et al (2014) The relationship between the Spine Deformity Index, biochemical parameters of bone metabolism and vascular calcifications: results from the Epidemiological VERtebral FRACtures iTalian Study (EVERFRACT) in dialysis patients. Clin Chem Lab Med 52:1595–1603PubMed Fusaro M, Gallieni M, Noale M et al (2014) The relationship between the Spine Deformity Index, biochemical parameters of bone metabolism and vascular calcifications: results from the Epidemiological VERtebral FRACtures iTalian Study (EVERFRACT) in dialysis patients. Clin Chem Lab Med 52:1595–1603PubMed
6.
Zurück zum Zitat Fusaro M. Gallieni M, Rebora P et al (2016) Atrial fibrillation and low vitamin D levels are associated with severe vascular calcifications in hemodialysis patients. J Nephrol 29:419–426CrossRefPubMed Fusaro M. Gallieni M, Rebora P et al (2016) Atrial fibrillation and low vitamin D levels are associated with severe vascular calcifications in hemodialysis patients. J Nephrol 29:419–426CrossRefPubMed
7.
Zurück zum Zitat Shearer MJ (2000) Role of vitamin K and GLA proteins in the pathophysiology of osteoporosis and vascular calcification. Curr Opin Clin Nutr Metab Care 3:433–438CrossRefPubMed Shearer MJ (2000) Role of vitamin K and GLA proteins in the pathophysiology of osteoporosis and vascular calcification. Curr Opin Clin Nutr Metab Care 3:433–438CrossRefPubMed
8.
Zurück zum Zitat Fusaro M, Noale M, Viola V et al (2012) Vitamin K, vertebral fractures, vascular calcifications, and mortality: vitamin K Italian (VIKI) dialysis study. J Bone Miner Res 27:2271–2278CrossRefPubMed Fusaro M, Noale M, Viola V et al (2012) Vitamin K, vertebral fractures, vascular calcifications, and mortality: vitamin K Italian (VIKI) dialysis study. J Bone Miner Res 27:2271–2278CrossRefPubMed
9.
Zurück zum Zitat Witteman JC, Grobbee DE, Valkenburg HA et al (1994) J-shaped relation between change in diastolic blood pressure and progression of aortic atherosclerosis. Lancet 343:504–507CrossRefPubMed Witteman JC, Grobbee DE, Valkenburg HA et al (1994) J-shaped relation between change in diastolic blood pressure and progression of aortic atherosclerosis. Lancet 343:504–507CrossRefPubMed
10.
Zurück zum Zitat Cranenburg EC, Vermeer C, Koos R et al (2008) The circulating inactive form of matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification. J Vasc Res 45:427–436CrossRefPubMed Cranenburg EC, Vermeer C, Koos R et al (2008) The circulating inactive form of matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification. J Vasc Res 45:427–436CrossRefPubMed
11.
Zurück zum Zitat Kraemer HC, Stice E, Kazdin A et al (2001) How do risk factors work together? Mediators, moderators, and independent, overlapping, and proxy risk factors. Am J Psychiatry 158:848–856CrossRefPubMed Kraemer HC, Stice E, Kazdin A et al (2001) How do risk factors work together? Mediators, moderators, and independent, overlapping, and proxy risk factors. Am J Psychiatry 158:848–856CrossRefPubMed
12.
Zurück zum Zitat Ferron M, Hinoi E, Karsenty G, Ducy P (2008) Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci USA 105:5266–5270CrossRefPubMed Ferron M, Hinoi E, Karsenty G, Ducy P (2008) Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci USA 105:5266–5270CrossRefPubMed
13.
Zurück zum Zitat Suksomboon N, Poolsup N, Ko HDKK (2017) Effect of vitamin K supplementation on insulin sensitivity: a meta-analysis. Diabetes, Metabolic Syndr Obes Targets Ther 10:169–177CrossRef Suksomboon N, Poolsup N, Ko HDKK (2017) Effect of vitamin K supplementation on insulin sensitivity: a meta-analysis. Diabetes, Metabolic Syndr Obes Targets Ther 10:169–177CrossRef
14.
Zurück zum Zitat Hussein AG, Mohamed RH, Shalaby SM, Abd El Motteleb DM (2018) Vitamin K2 alleviates type 2 diabetes in rats by induction of osteocalcin gene expression. Nutrition 47:33–38CrossRefPubMed Hussein AG, Mohamed RH, Shalaby SM, Abd El Motteleb DM (2018) Vitamin K2 alleviates type 2 diabetes in rats by induction of osteocalcin gene expression. Nutrition 47:33–38CrossRefPubMed
15.
Zurück zum Zitat Choi HJ, Yu J, Choi H et al (2011) Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial. Diabetes Care 34:e147CrossRefPubMedPubMedCentral Choi HJ, Yu J, Choi H et al (2011) Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial. Diabetes Care 34:e147CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Luo XH, Zhao LL, Yuan LQ, Wang M, Xie H, Liao EY (2009) Development of arterial calcification in adiponectin-deficient mice: adiponectin regulates arterial calcification. J Bone Miner Res 24:1461–1468CrossRefPubMed Luo XH, Zhao LL, Yuan LQ, Wang M, Xie H, Liao EY (2009) Development of arterial calcification in adiponectin-deficient mice: adiponectin regulates arterial calcification. J Bone Miner Res 24:1461–1468CrossRefPubMed
17.
Zurück zum Zitat Confavreux CB, Szulc P, Casey R et al (2013) Higher serum osteocalcin is associated with lower abdominal aortic calcification progression and longer 10-year survival in elderly men of the MINOS cohort. J Clin Endocrinol Metab 98:1084–1092CrossRefPubMed Confavreux CB, Szulc P, Casey R et al (2013) Higher serum osteocalcin is associated with lower abdominal aortic calcification progression and longer 10-year survival in elderly men of the MINOS cohort. J Clin Endocrinol Metab 98:1084–1092CrossRefPubMed
18.
Zurück zum Zitat Bendix EF, Johansen E, Ringgaard T, Wolder M, Starup-Linde J (2018) Diabetes and abdominal aortic calcification—a systematic review. Curr Osteoporos Rep 16:42–57CrossRefPubMed Bendix EF, Johansen E, Ringgaard T, Wolder M, Starup-Linde J (2018) Diabetes and abdominal aortic calcification—a systematic review. Curr Osteoporos Rep 16:42–57CrossRefPubMed
19.
Zurück zum Zitat Parker BD, Ix JH, Cranenburg EC et al (2009) Association of kidney function and uncarboxylated matrix Gla protein: data from the Heart and Soul Study. Nephrol Dial Transpl 24:2095–2101CrossRef Parker BD, Ix JH, Cranenburg EC et al (2009) Association of kidney function and uncarboxylated matrix Gla protein: data from the Heart and Soul Study. Nephrol Dial Transpl 24:2095–2101CrossRef
20.
Zurück zum Zitat Fusaro M, Tripepi G, Noale M et al (2015) Prevalence of vertebral fractures, vascular calcifications, and mortality in warfarin treated hemodialysis patients. Curr Vasc Pharmacol 13:248–258CrossRefPubMed Fusaro M, Tripepi G, Noale M et al (2015) Prevalence of vertebral fractures, vascular calcifications, and mortality in warfarin treated hemodialysis patients. Curr Vasc Pharmacol 13:248–258CrossRefPubMed
21.
Zurück zum Zitat Nakashima A, Yokoyama K, Yokoo T, Urashima M (2016) Role of vitamin D in diabetes mellitus and chronic kidney disease. World J Diabetes 7:89–100CrossRefPubMedPubMedCentral Nakashima A, Yokoyama K, Yokoo T, Urashima M (2016) Role of vitamin D in diabetes mellitus and chronic kidney disease. World J Diabetes 7:89–100CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Fusaro M, Giannini S, Gallieni M et al (2016) Calcimimetic and vitamin D analog use in hemodialyzed patients is associated with increased levels of vitamin K dependent proteins. Endocrine 51:333–341CrossRefPubMed Fusaro M, Giannini S, Gallieni M et al (2016) Calcimimetic and vitamin D analog use in hemodialyzed patients is associated with increased levels of vitamin K dependent proteins. Endocrine 51:333–341CrossRefPubMed
Metadaten
Titel
Osteocalcin (bone GLA protein) levels, vascular calcifications, vertebral fractures and mortality in hemodialysis patients with diabetes mellitus
verfasst von
Maria Fusaro
Maurizio Gallieni
Andrea Aghi
Maria Antonietta Rizzo
Giorgio Iervasi
Thomas L. Nickolas
Fabrizio Fabris
Maria Cristina Mereu
Sandro Giannini
Stefania Sella
Andrea Giusti
Annalisa Pitino
Graziella D’Arrigo
Maurizio Rossini
Davide Gatti
Maura Ravera
Luca Di Lullo
Antonio Bellasi
Giuliano Brunori
Antonio Piccoli
Giovanni Tripepi
Mario Plebani
Publikationsdatum
01.08.2019
Verlag
Springer International Publishing
Erschienen in
Journal of Nephrology / Ausgabe 4/2019
Print ISSN: 1121-8428
Elektronische ISSN: 1724-6059
DOI
https://doi.org/10.1007/s40620-019-00595-1

Weitere Artikel der Ausgabe 4/2019

Journal of Nephrology 4/2019 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

29.05.2024 Herzinfarkt Nachrichten

Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.