Circulating nonphosphorylated carboxylated matrix gla protein predicts survival in ESRD.

Abstract

The mechanisms for vascular calcification and its associated cardiovascular mortality in patients with ESRD are not completely understood. Dialysis patients exhibit profound vitamin K deficiency, which may impair carboxylation of the calcification inhibitor matrix gla protein (MGP). Here, we tested whether distinct circulating inactive vitamin K-dependent proteins associate with all-cause or cardiovascular mortality. We observed higher levels of both desphospho-uncarboxylated MGP (dp-ucMGP) and desphospho-carboxylated MGP (dp-cMGP) among 188 hemodialysis patients compared with 98 age-matched subjects with normal renal function. Levels of dp-ucMGP correlated with those of protein induced by vitamin K absence II (PIVKA-II; r = 0.62, P < 0.0001). We found increased PIVKA-II levels in 121 (64%) dialysis patients, indicating pronounced vitamin K deficiency. Kaplan-Meier analysis showed that patients with low levels of dp-cMGP had an increased risk for all-cause and cardiovascular mortality. Multivariable Cox regression confirmed that low levels of dp-cMGP increase mortality risk (all-cause: HR, 2.2; 95% CI, 1.1 to 4.3; cardiovascular: HR, 2.7; 95% CI, 1.2 to 6.2). Furthermore, patients with higher vascular calcification scores showed lower levels of dp-cMGP. In 17 hemodialysis patients, daily supplementation with vitamin K2 for 6 weeks reduced dp-ucMGP levels by 27% (P = 0.003) but did not affect dp-cMGP levels. In conclusion, the majority of dialysis patients exhibit pronounced vitamin K deficiency. Lower levels of circulating dp-cMGP may serve as a predictor of mortality in dialysis patients. Whether vitamin K supplementation improves outcomes requires further study.

• Authors: Georg Schlieper, Ralf Westenfeld, Thilo Krüger, Ellen C Cranenburg, Elke J Magdeleyns, Vincent M Brandenburg, Zivka Djuric, Tatjana Damjanovic, Markus Ketteler, Cees Vermeer, Nada Dimkovic, Jürgen Floege, Leon J Schurgers
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 22 Issue 2 Pg. 387-95 (Feb 2011) ISSN: 1533-3450 [Electronic] United States
• PMID: 21289218 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Calcium-Binding Proteins
• Extracellular Matrix Proteins
• Protein Precursors
• matrix Gla protein
• Vitamin K 2
• acarboxyprothrombin
• Prothrombin

Topics

• Adult
• Aged
• Biomarkers (blood)
• Calcinosis (blood)
• Calcium-Binding Proteins (blood)
• Extracellular Matrix Proteins (blood)
• Female
• Humans
• Kidney Failure, Chronic (blood, mortality)
• Male
• Middle Aged
• Phosphorylation
• Proportional Hazards Models
• Prospective Studies
• Protein Precursors (blood)
• Prothrombin
• Renal Dialysis (mortality)
• Vitamin K 2 (administration & dosage)