Journal Mobile Options
Table of Contents
Vol. 25, No. 5-6, 2007
Issue release date: January 2008
Blood Purif 2007;25:395–401

Undercarboxylated Matrix GLA Protein Levels Are Decreased in Dialysis Patients and Related to Parameters of Calcium-Phosphate Metabolism and Aortic Augmentation Index

Hermans M.M.H. · Vermeer C. · Kooman J.P. · Brandenburg V. · Ketteler M. · Gladziwa U. · Rensma P.L. · Leunissen K.M.L. · Schurgers L.J.
aDepartment of Internal Medicine and Nephrology, Academic Hospital Maastricht, bCardiovascular Research Institute CARIM, cVitak BV, University of Maastricht, Maastricht, and dDepartment of Internal Medicine and Nephrology, Elisabeth Hospital, Tilburg, The Netherlands; eUniversity of Witten-Herdecke, Witten, and fDepartment of Nephrology and Clinical Immunology, University Hospital RWTH, Aachen, Germany

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background: Vascular calcifications are related to cardiovascular mortality and morbidity in dialysis patients. Limited data exist on the role of calcification inhibitors, such as matrix-carboxyglutamic acid protein (MGP) in dialysis patients. Methods: In 120 dialysis patients and 41 age-matched healthy controls, circulating undercarboxylated (uc) MGP levels were measured with a novel ELISA-based competitive assay. The association between ucMGP levels and determinants of bone mineral metabolism, including the calcification inhibitor fetuin-A, was studied. Moreover, the relation between ucMGP levels and arterial stiffness was investigated. Results: The ucMGP level was significantly lower in dialysis patients compared to controls (173 ± 70 vs. 424 ± 126 nmol/l; p < 0.0001). After adjustment for age, sex and duration of dialysis an independent negative association between time-averaged phosphate levels [regression coefficient β with 95% confidence interval = –64 (–107 to –21)] and a positive association between serum ucMGP and fetuin-A [131 (55–208)] was observed. Duration of dialysis was inversely correlated with ucMGP (r = –0.24, p = 0.007). ucMGP levels were not related to high-sensitivity C-reactive protein or time-averaged calcium levels. After adjustment for age, sex, cardiovascular disease, diabetes, height and mean arterial pressure, ucMGP level was negatively associated with the aortic augmentation index [–0.036 (–0.061 to –0.010)] but not with pulse wave velocity or pulse pressure. Conclusion: Significantly lower serum ucMGP levels were observed in dialysis patients compared to healthy controls. ucMGP levels were inversely associated with phosphate and positively associated with serum fetuin-A levels. Furthermore, ucMGP levels were inversely associated with the aortic augmentation index. These data suggest that low ucMGP levels may be a marker of active calcification.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Guerin AP, London GM, Marchais SJ, Metivier F: Arterial stiffening and vascular calcifications in end-stage renal disease. Nephrol Dial Transplant 2000;15:1014–1021.
  2. Jono S, Shioi A, Ikari Y, Nishizawa Y: Vascular calcification in chronic kidney disease. J Bone Miner Metab 2006;24:176–181.
  3. Shanahan CM: Vascular calcification – a matter of damage limitation? Nephrol Dial Transplant 2006;21:1166–1169.
  4. Ketteler M, Schlieper G, Floege J: Calcification and cardiovascular health: new insights into an old phenomenon. Hypertension 2006;47:1027–1034.
  5. Ketteler M, Vermeer C, Wanner C, Westenfeld R, Jahnen-Dechent W, Floege J: Novel insights into uremic vascular calcification: role of matrix Gla protein and alpha-2-Heremans Schmid glycoprotein/fetuin. Blood Purif 2002;20:473–476.
  6. Ketteler M, Bongartz P, Westenfeld R, Wildberger JE, Mahnken AH, Bohm R, Metzger T, Wanner C, Jahnen-Dechent W, Floege J: Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study. Lancet 2003;361:827–833.
  7. Stenvinkel P, Wang K, Qureshi AR, Axelsson J, Pecoits-Filho R, Gao P, Barany P, Lindholm B, Jogestrand T, Heimburger O, Holmes C, Schalling M, Nordfors L: Low fetuin-A levels are associated with cardiovascular death: impact of variations in the gene encoding fetuin. Kidney Int 2005;67:2383–2392.
  8. Hermans MM, Brandenburg V, Ketteler M, Kooman JP, van der Sande FM, Gladziwa U, Rensma PL, Bartelet K, Konings CJ, Hoeks AP, Floege J, Leunissen KM: Study on the relationship of serum fetuin-A concentration with aortic stiffness in patients on dialysis. Nephrol Dial Transplant 2006;21:1293–1299.
  9. Schurgers LJ, Teunissen KJ, Knapen MH, Kwaijtaal M, van Diest R, Appels A, Reutelingsperger CP, Cleutjens JP, Vermeer C: Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid (Gla) protein: undercarboxylated matrix Gla protein as marker for vascular calcification. Arterioscler Thromb Vasc Biol 2005;25:1629–1633.
  10. Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G: Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 1997;386:78–81.
  11. Brancaccio D, Biondi ML, Gallieni M, Turri O, Galassi A, Cecchini F, Russo D, Andreucci V, Cozzolino M: Matrix GLA protein gene polymorphisms: clinical correlates and cardiovascular mortality in chronic kidney disease patients. Am J Nephrol 2005;25:548–552.
  12. Price PA, Chan WS, Jolson DM, Williamson MK: The elastic lamellae of devitalized arteries calcify when incubated in serum: evidence for a serum calcification factor. Arterioscler Thromb Vasc Biol 2006;26:1079–1085.
  13. Spronk HM, Soute BA, Schurgers LJ, Thijssen HH, De Mey JG, Vermeer C: Tissue-specific utilization of menaquinone-4 results in the prevention of arterial calcification in warfarin-treated rats. J Vasc Res 2003;40:531–537.
  14. Koos R, Mahnken AH, Muhlenbruch G, Brandenburg V, Pflueger B, Wildberger JE, Kuhl HP: Relation of oral anticoagulation to cardiac valvular and coronary calcium assessed by multislice spiral computed tomography. Am J Cardiol 2005;96:747–749.
  15. Schurgers LJ, Aebert H, Vermeer C, Bultmann B, Janzen J: Oral anticoagulant treatment: friend or foe in cardiovascular disease? Blood 2004;104:3231–3232.
  16. Ix JH, Shlipak MG, Brandenburg VM, Ali S, Ketteler M, Whooley MA: Association between human fetuin-A and the metabolic syndrome: data from the Heart and Soul Study. Circulation 2006;113:1760–1767.
  17. Pannier BM, Avolio AP, Hoeks A, Mancia G, Takazawa K: Methods and devices for measuring arterial compliance in humans. Am J Hypertens 2002;15:743–753.
  18. Farzaneh-Far A, Davies JD, Braam LA, Spronk HM, Proudfoot D, Chan SW, O’Shaughnessy KM, Weissberg PL, Vermeer C, Shanahan CM: A polymorphism of the human matrix gamma-carboxyglutamic acid protein promoter alters binding of an activating protein-1 complex and is associated with altered transcription and serum levels. J Biol Chem 2001;276:32466–32473.
  19. Giachelli CM, Jono S, Shioi A, Nishizawa Y, Mori K, Morii H: Vascular calcification and inorganic phosphate. Am J Kidney Dis 2001;38:S34–S37.
  20. Jono S, McKee MD, Murry CE, Shioi A, Nishizawa Y, Mori K, Morii H, Giachelli CM: Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 2000;87:E10–E17.
  21. Chertow GM, Raggi P, Chasan-Taber S, Bommer J, Holzer H, Burke SK: Determinants of progressive vascular calcification in haemodialysis patients. Nephrol Dial Transplant 2004;19:1489–1496.
  22. Reynolds JL, Skepper JN, McNair R, Kasama T, Gupta K, Weissberg PL, Jahnen-Dechent W, Shanahan CM: Multifunctional roles for serum protein fetuin-a in inhibition of human vascular smooth muscle cell calcification. J Am Soc Nephrol 2005;16:2920–2930.
  23. Davies JI, Struthers AD: Pulse wave analysis and pulse wave velocity: a critical review of their strengths and weaknesses. J Hypertens 2003;21:463–472.
  24. London GM, Blacher J, Pannier B, Guerin AP, Marchais SJ, Safar ME: Arterial wave reflections and survival in end-stage renal failure. Hypertension 2001;38:434–438.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50