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Vitamin K2 MK- 7 not as available if have Chronic Kidney Disease - Nov 2021

Altered vitamin K biodistribution and metabolism in experimental and human chronic kidney disease.

Kidney International online 11 November 2021, https://doi.org/10.1016/j.kint.2021.10.029
NadineKaeslerPhD12FelixSchreibingMD12ThimoteusSpeerMD, PhD34Sofia de laPuente-SecadesM.Sc5NikolasRappM.Sc6ChristianeDrechslerMD7NazaninKabganiPhD2ChristophKuppeMD12PeterBoorMD, PhD81VeraJankowskiPhD5LeonSchurgersPhD126RafaelKramannMD, PhD129∗JürgenFloegeMD1∗

Chronic kidney disease (CKD) is accompanied with extensive cardiovascular calcification, in part correlating with functional vitamin K deficiency. Here, we sought to determine causes for vitamin K deficiency beyond reduced dietary intake. Initially, vitamin K uptake and distribution into circulating lipoproteins after a single administration of vitamin K1 plus K2 (menaquinone 4 and menaquinone 7, respectively) was determined in patients on dialysis therapy and healthy individuals.

The patients incorporated very little menaquinone 7 but more menaquinone 4 into high density lipoprotein (HDL) and low density lipoprotein particles than did healthy individuals.

In contrast to healthy persons, HDL particles from the patients could not be spiked with menaquinone 7 in vitro and HDL uptake was diminished in osteoblasts. A reduced carboxylation activity (low vitamin K activity) of uremic HDL particles spiked with menaquinone 7 vs. that of controls was confirmed in a bioassay using human primary vascular smooth muscle cells. Kidney menaquinone 4 tissue levels were reduced in 5/6-nephrectomized versus sham-operated C57BL/6 mice after four weeks of a vitamin K rich diet. From the analyzed enzymes involved in vitamin K metabolism, kidney HMG-CoA reductase protein was reduced in both rats and patients with CKD. In a trial on the efficacy and safety of atorvastatin in 1051 patients with type 2 diabetes receiving dialysis therapy, no pronounced vitamin K deficiency was noted. However, the highest levels of PIVKA-II (biomarker of subclinical vitamin K deficiency) were noted when a statin was combined with a proton pump inhibitor.

Thus, profound disturbances in lipoprotein mediated vitamin K transport and metabolism in uremia suggest that menaquinone 7 supplementation to patients on dialysis therapy has reduced efficacy.
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