Abstract
Vascular calcification (VC) is highly prevalent in Chronic Kidney Disease (CKD) patients, progresses gradually with deterioration of kidney function and is a strong, independent predictor of cardiovascular (CV) mortality. Matrix Gla Protein (MGP), the most potent inhibitor of VC, requires vitamin K as a co-factor to become biologically active. Accumulating epidemiological data have associated vitamin K depletion with VC progression and CV outcomes. CKD patients are characterized by poor vitamin K status and at the same time, pronounced CV calcification. In early and advanced CKD, including end-stage kidney disease, exogenous supplementation of vitamin K (especially with menaquinone 7, its most bioavailable form) might decrease the inactive form of MGP (dephosphorylated, uncarboxylated MGP) and probably retard the progression or even reverse VC. Here, we focus and discuss the interventional human studies of vitamin K supplementation in CKD patients and suggest future directions in this area of interest.
Keywords: Chronic kidney disease, dephosphorylated uncarboxylated MGP, end stage kidney disease, matrix gla protein, vascular calcification, vitamin K2.
Graphical Abstract
[http://dx.doi.org/10.1681/ASN.2004030203] [PMID: 15590763]
[http://dx.doi.org/10.1046/j.1523-1755.2003.00838.x] [PMID: 12631096]
[http://dx.doi.org/10.1038/ki.2008.458] [PMID: 18800030]
[http://dx.doi.org/10.1016/bs.acc.2020.02.004] [PMID: 32564789]
[http://dx.doi.org/10.1111/j.1525-139X.2007.00257.x] [PMID: 17374084]
[http://dx.doi.org/10.1038/386078a0] [PMID: 9052783]
[http://dx.doi.org/10.3390/ijms21176035] [PMID: 32839405]
[http://dx.doi.org/10.1016/j.jdiacomp.2017.06.012] [PMID: 28734846]
[http://dx.doi.org/10.3390/ijms20030628] [PMID: 30717170]
[http://dx.doi.org/10.1681/ASN.2010040339] [PMID: 21289218]
[http://dx.doi.org/10.1186/1471-2369-15-145] [PMID: 25190488]
[http://dx.doi.org/10.1093/ajh/hpy079] [PMID: 29788226]
[http://dx.doi.org/10.1159/000453368] [PMID: 27951533]
[http://dx.doi.org/10.1111/bjh.13828] [PMID: 26492096]
[http://dx.doi.org/10.1093/jn/134.11.3100] [PMID: 15514282]
[http://dx.doi.org/10.3390/nu9121334] [PMID: 29292751]
[http://dx.doi.org/10.1016/j.clnu.2014.03.011] [PMID: 24745600]
[http://dx.doi.org/10.2174/1570161118666200320111745] [PMID: 32196451]
[http://dx.doi.org/10.1182/blood-2006-07-035345] [PMID: 17138823]
[http://dx.doi.org/10.1038/ki.2013.530] [PMID: 24429407]
[http://dx.doi.org/10.1159/000075344] [PMID: 14654717]
[http://dx.doi.org/10.3390/nu7085318] [PMID: 26295257]
[http://dx.doi.org/10.1053/j.ajkd.2011.10.041] [PMID: 22169620]
[http://dx.doi.org/10.1093/ndt/gft464] [PMID: 24285428]
[http://dx.doi.org/10.1186/s12882-017-0609-3] [PMID: 28592319]
[PMID: 2304704]
[http://dx.doi.org/10.20452/pamw.3041] [PMID: 26176325]
[http://dx.doi.org/10.1016/j.jash.2017.07.001] [PMID: 28756183]
[http://dx.doi.org/10.1681/ASN.2020020225] [PMID: 32817311]
[http://dx.doi.org/10.1160/TH14-08-0675] [PMID: 25694037]
[http://dx.doi.org/10.1007/s11255-019-02275-2] [PMID: 31529295]
[http://dx.doi.org/10.1186/s12882-017-0560-3] [PMID: 28464802]
[http://dx.doi.org/10.1681/ASN.2019060579] [PMID: 31704740]
[http://dx.doi.org/10.3389/fmed.2020.00154] [PMID: 32391368]
[http://dx.doi.org/10.1136/openhrt-2019-001070] [PMID: 32675297]
[http://dx.doi.org/10.1186/s40697-015-0053-x] [PMID: 26075081]
[http://dx.doi.org/10.1093/ndt/gft459] [PMID: 24285427]
[http://dx.doi.org/10.1007/s00394-020-02469-w] [PMID: 33532875]
[http://dx.doi.org/10.2174/1570161118666200317151553] [PMID: 32183680]