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

Background: 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. Methods: 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. Results: 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). Conclusion: 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.