Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Evaluation of inactive Matrix-Gla-Protein (MGP) as a biomarker for incident and recurrent kidney stones



Matrix-Gla-protein (MGP) is an inhibitor of vascular calcification. Its dephosphorylated and uncarboxylated inactive form, dpucMGP, is a marker of vitamin K status and of cardio-vascular outcomes in chronic kidney disease. We hypothesized that higher serum dpucMGP would be a biomarker of kidney stone disease.


We measured serum dpucMGP in incident symptomatic kidney stone-formers and non-stone formers at a baseline visit. Symptomatic stone recurrence was assessed in the stones formers over a 5-year period. The association of dpucMGP with incident or recurrent kidney stones was assessed with and without adjustment for clinical, blood, and urine characteristics.


There was no significant difference in serum dpucMGP level between 498 stone formers and 395 non-stone former (510 vs 501 pmol/L; p = 0.66). In a multivariable model adjusting for clinical, blood and urine chemistries, higher MGP was associated with lower risk of stone formation (OR = 0.674, 95% CI 0.522–0.870), contrary to previous reports. Among 375 stone formers with 5 years of follow-up, 79 (21%) had symptomatic recurrence. No difference in serum dpucMGP was evident in recurrent versus non-recurrent stone-formers (482 vs 502 pmol/L; p = 0.26). Serum dpucMGP was correlated with cystatin C levels in non stone-formers, incident stone-formers and recurrent stone-formers (r > 0.3, p < 0.0001).


Elevated serum dpucMGP was not associated with incident or recurrent symptomatic kidney stone events. However, higher level of dpucMGP was associated with lower risk of kidney stone in a multivariable logistic regression model.

This is a preview of subscription content, log in to check access.

Fig. 1


  1. 1.

    Hale JE, Fraser JD, Price PA (1988) The identification of matrix Gla protein in cartilage. J Biol Chem 263:5820–5824

  2. 2.

    Evrard S, Delanaye P, Kamel S et al (2014) Vascular calcification: From pathophysiology to biomarkers. Clin Chim Acta 438:401–414.

  3. 3.

    Schurgers LJ, Cranenburg ECM, Vermeer C (2008) Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb Haemost 100:593–603

  4. 4.

    Delanaye P, Liabeuf S, Bouquegneau A et al (2015) The matrix-gla protein awakening may lead to the demise of vascular calcification. Nephrol Ther 11:191–200.

  5. 5.

    Delanaye P, Krzesinski J-M, Warling X et al (2014) Dephosphorylated-uncarboxylated Matrix Gla protein concentration is predictive of vitamin K status and is correlated with vascular calcification in a cohort of hemodialysis patients. BMC Nephrol 15:145.

  6. 6.

    Dalmeijer GW, Van der Schouw YT, Vermeer C et al (2013) Circulating matrix Gla protein is associated with coronary artery calcification and vitamin K status in healthy women. J Nutr Biochem 24:624–628.

  7. 7.

    Liabeuf S, Olivier B, Vemeer C et al (2014) Vascular calcification in patients with type 2 diabetes: the involvement of matrix Gla protein. Cardiovasc Diabetol 13:85.

  8. 8.

    Gao B, Yasui T, Lu X et al (2010) Matrix Gla protein expression in NRK-52E cells exposed to oxalate and calcium oxalate monohydrate crystals. Urol Int 85:237–241.

  9. 9.

    Lu X, Gao B, Yasui T et al (2013) Matrix Gla protein is involved in crystal formation in kidney of hyperoxaluric rats. Kidney Blood Press Res 37:15–23.

  10. 10.

    Lu X, Gao B, Liu Z et al (2012) A polymorphism of matrix Gla protein gene is associated with kidney stone in the Chinese Han population. Gene 511:127–130.

  11. 11.

    Wei F-F, Thijs L, Zhang Z-Y, et al (2017) The risk of nephrolithiasis is causally related to inactive matrix Gla protein, a marker of vitamin K status: a Mendelian randomization study in a Flemish population. Nephrol Dial Transpl.

  12. 12.

    Haley WE, Enders FT, Vaughan LE et al (2016) Kidney function after the first kidney stone event. Mayo Clin Proc 91:1744–1752.

  13. 13.

    Khan A, Wang W, Khan SR (2014) Calcium oxalate nephrolithiasis and expression of matrix GLA protein in the kidneys. World J Urol 32:123–130.

  14. 14.

    Khan SR, Joshi S, Wang W, Peck AB (2014) Regulation of macromolecular modulators of urinary stone formation by reactive oxygen species: transcriptional study in an animal model of hyperoxaluria. Am J Physiol Renal Physiol 306:F1285–F1295.

  15. 15.

    Joshi S, Clapp WL, Wang W, Khan SR (2015) Osteogenic changes in kidneys of hyperoxaluric rats. Biochim Biophys Acta Mol Basis Dis 1852:2000–2012.

  16. 16.

    Yasui T, Fujita K, Sasaki S, et al (1999) Expression of bone matrix proteins in urolithiasis model rats. Urol Res 27:255–261

  17. 17.

    Wang Q, Hu H, Dirie NI et al (2018) High concentration of calcium promotes mineralization in NRK52E cells via inhibiting the expression of matrix Gla protein. Urology.

  18. 18.

    Dalmeijer GW, van der Schouw YT, Magdeleyns E et al (2012) The effect of menaquinone-7 supplementation on circulating species of matrix Gla protein. Atherosclerosis 225:397–402.

  19. 19.

    Goiko M, Dierolf J, Gleberzon JS et al (2013) Peptides of Matrix Gla protein inhibit nucleation and growth of hydroxyapatite and calcium oxalate monohydrate crystals. PLoS One 8:e80344.

  20. 20.

    Singh P, Enders FT, Vaughan LE et al (2015) Stone composition among first-time symptomatic kidney stone formers in the community. Mayo Clin Proc 90:1356–1365.

  21. 21.

    Murugesan A, Kumar L, Janarthanan P (2018) Status of single nucleotide polymorphism of matrix gla protein gene (rs4236) in Nephrolithiasis: a preliminary study in indian population. Int J Appl Basic Med Res 8:38.

  22. 22.

    Gao B, Yasui T, Itoh Y et al (2007) A polymorphism of matrix Gla protein gene is associated with kidney stones. J Urol 177:2361–2365.

  23. 23.

    Zhu M, Zeng F, Cui Y, et al (2017) Expression of matrix Gla protein and bone morphogenetic protein 2 in renal papillary tissues in patients with calcium oxalate kidney stones. J Cent South Univ Med Sci 42:277–283.

  24. 24.

    Puzantian H, Akers SR, Oldland G et al (2018) Circulating dephospho-uncarboxylated matrix gla-protein is associated with kidney dysfunction and arterial stiffness. Am J Hypertens 31:988–994.

  25. 25.

    Kurnatowska I, Grzelak P, Masajtis-Zagajewska A et al (2016) Plasma desphospho-uncarboxylated matrix gla protein as a marker of kidney damage and cardiovascular risk in advanced stage of chronic kidney disease. Kidney Blood Press Res 41:231–239.

  26. 26.

    Sorensen MD, Hsi RS, Chi T et al (2014) Dietary intake of fiber, fruit and vegetables decreases the risk of incident kidney stones in women: a women’s health initiative report. J Urol 192:1694–1699.

Download references


The authors would like to thanks IDS for providing the MGP reagents.

Author information

Correspondence to Vincent Castiglione.

Ethics declarations

Conflict of interest

PD and EC declare honoraria of consultancy for IDS. The results presented in this paper have not been published previously in whole or part, except in abstract format.

Ethical approval

This study is in accordance with the 1964 Declaration of Helsinki and has been approved by the Mayo Clinic Institutional Review Board (IRB:08–006541).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Castiglione, V., Pottel, H., Lieske, J.C. et al. Evaluation of inactive Matrix-Gla-Protein (MGP) as a biomarker for incident and recurrent kidney stones. J Nephrol 33, 101–107 (2020).

Download citation


  • Nephrolithiais
  • Matrix-Gla-protein
  • Biomarker
  • Cystatin C