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.
KeywordsNephrolithiais Matrix-Gla-protein Biomarker Cystatin C
The authors would like to thanks IDS for providing the MGP reagents.
Compliance with ethical standards
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.
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 was obtained from all individual participants included in the study.
- 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. https://doi.org/10.1186/1471-2369-15-145 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1152/ajprenal.00057.2014 CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1016/j.atherosclerosis.2012.09.019 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.11817/j.issn.1672-7347.2017.03.007 CrossRefGoogle Scholar
- 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. https://doi.org/10.1159/000443426 CrossRefPubMedGoogle Scholar