Document Detail

Circulating nonphosphorylated carboxylated matrix gla protein predicts survival in ESRD.
MedLine Citation:
PMID:  21289218     Owner:  NLM     Status:  MEDLINE    
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.
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
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  22     ISSN:  1533-3450     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-03     Completed Date:  2011-03-17     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  387-95     Citation Subset:  IM    
Department of Nephrology and Clinical Immunology, Rheinisch-Westfälische Technische Hochschule, Pauwelsstrasse 30, 52074 Aachen, Germany.
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MeSH Terms
Biological Markers / blood
Calcinosis / blood
Calcium-Binding Proteins / blood*
Extracellular Matrix Proteins / blood*
Kidney Failure, Chronic / blood,  mortality*
Middle Aged
Proportional Hazards Models
Prospective Studies
Protein Precursors / blood
Renal Dialysis / mortality
Vitamin K 2 / administration & dosage
Reg. No./Substance:
0/Biological Markers; 0/Calcium-Binding Proteins; 0/Extracellular Matrix Proteins; 0/Protein Precursors; 0/matrix Gla protein; 11032-49-8/Vitamin K 2; 53230-14-1/acarboxyprothrombin; 9001-26-7/Prothrombin

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