LAUSR

Objective: Matrix Gla protein (MGP) is a small protein for the protection of vascular calcification. High circulating desphospho-uncarboxylated MGP (dp-ucMGP), indicative of poor vitamin K status, has been associated with renal dysfunction and mortality. However, whether the impaired renal clearance would contribute to high dp-ucMGP and confound these associations remains unclear. Design and method: We measured urinary MGP using capillary electrophoresis coupled with mass spectrometry in 776 Flemish (mean age: 51.2 years; 50.9% women), of whom 646 were assayed for plasma dp-ucMGP. The endpoint was defined as mortality or fatal and nonfatal cardiovascular events. Statistical analyses included Spearman correlation, linear regression, and Cox proportional hazard models. Results: Urinary MGP was neither correlated with serum creatinine (P = 0.15) nor associated with estimated glomerular filtration rate (eGFR) after adjustment (P = 0.057). Circulating dp-ucMGP was correlated with urinary MGP and eGFR (r = 0.40 and -0.40, P < 0.0001) and their association remained significant after adjustment (P < 0.0001). Over 9.2 (median) years, 47 individuals died, including 15 cardiovascular deaths. For a doubling of urinary MGP, the hazard ratios (HRs) were 1.45 (95% confidence interval [CI]: 1.11–1.90, P = 0.007) for all-cause mortality, 2.31 (1.21–4.43, P = 0.011) for cardiovascular mortality after adjustment for eGFR and other clinical risk factors. For dp-ucMGP, the corresponding adjusted HRs were 2.13 (1.31–3.48, P = 0.003) and 1.52 (0.66–3.53, P = 0.33). Neither urinary MGP nor dp-ucMGP was significantly associated with cardiovascular events after adjustment (P> = 0.88). Urinary MGP further improved the prognostic accuracy for all-cause mortality, as suggested by the increased net reclassification improvement (64.1% [32.8–94.6], P < 0.0001) and integrated discrimination improvement (4.6% [0.9–9.0], P = 0.012). Conclusions: The association of high circulating dp-ucMGP with decreased renal function might be driven by vitamin K deficiency and vascular calcification, instead of by impaired renal clearance. Urinary MGP might serve as a novel marker for vitamin K status and mortality.