# Vitamin K Status of Patients Undergoing Hemodialysis: Insights from a Cross-Sectional Study
## 4 Discussion
The association between the level of VKDP and the presence of vascular calcifications, and also with the endpoint of cardiovascular or all-cause mortality, has been shown across numerous cross-sectional or prospective studies performed on CKD patients [23; 24; 25]. In our study, we did not find any significant correlation between previous cardiovascular events (stroke or coronary heart disease) and the levels of dp-uc MGP and total OC. This a surprising finding given the fact that cardiovascularevents in dialysis patients rely on accelerated atherosclerosis and vascular calcifications as an underlying pathophysiologic mechanism [19]. Another significant part of our study is linked to the relationship of the studied parameters (total OC and dp-uc MGP) with different concomitant medications. Regarding the CKD-MBD treatment, we observed significant associations between dp-uc MGP (and not the total OC) and non-calcium-based phosphate binders and paralcitol. [PERSON] et al. [26] performed an in vitro study regarding the interaction between different phosphate binders and vitamin K2. They showed that succroferric-oxyhydroxic and sevelamer carbonate were the only medications that did not bind vitamin K2, while calcium-based phosphate binders and lanthanum carbonate ligate vitamin K2. Similar to our results, the VIKI study [21] also observed the link between concomitant treatments for CKD-MBD versus the OC and MGP levels. They observed that vitamin D analogs (such as paralcitol) increase the levels of OC and MGP. The potential link between CKD MBD and vitamin K2 metabolism may be of particular clinical interest given the fact that the choice of medication should take into account the prevention of vascular calcifications as well. The studies regarding this topic are, however, scarce, and further RCTs would be useful to determine the benefit of choosing certain medication classes over others. Another class of drugs frequently used by patients treated with HD is anticoagulants. In our study, patients treated with vitamin K antagonists (VKA) showed higher levels of dp-uc MGP (\(p<0.001\)). This result is concordant with the available literature [27]. Considering this mechanism, patients on dialysis who are already vitamin K-deficient and take warfarin are much more prone to develop vascular calcifications [28]. [PERSON] et al. conducted a meta-analysis of patients with ESRD and atrial fibrillation and found that 22% were on warfarin treatment [29]. In the context of extensive warfarin use and CKD MBD in ESRD patients, vitamin K supplementation was mitigated to have potential benefits. Neither the RenaKvit study [30] nor the Valkyrie study [31] have showed that vitamin K2 supplementation in clinical practice can reduce vascular stiffness or calcifications in dialysis patients, and neither did the VIKTORIES trial [32] on transplanted patients. Thus, there is no evidence yet to support the protective effects of vitamin K supplementation against vascular calcification in CKD patients as it has been also proven in a recently published metanalysis [33]. Regarding anticoagulation in patients on HD, considering the potential harmful effects of VKA, the question is if they could be replaced with direct oral anticoagulants (DOAC). There is no evidence that DOAC therapy would be unsafe or less effective than VKA, but most studies are retrospective studies. There are however two RCTs showing the non-inferiority of DOAC (apixaban) vs. VKAs in hemodialysis patients regarding safety and efficacy [34,35] and one RCT (rivaroxaban vs. VKA) that shows a superior risk-benefit profile of DOACs versus VKAs, and this suggests that VKAs should be avoided by patients on HD [36]. The major limitations of our study are that it is a cross-sectional analysis, single-centered and used a small group of subjects. Another limitation of the study could be the fact that we determined the total OC and not the specific inactive fragments.