Vitamin K1 and progression of cardiovascular calcifications in hemodialysis patients: the VitaVasK randomized controlled trial.

Background: Cardiovascular calcifications are prevented by matrix Gla protein (MGP), a vitamin K-dependent protein. Haemodialysis patients exhibit marked vitamin K deficiency. The randomized, prospective, open-label, multicentre VitaVasK trial analysed whether vitamin K1 supplementation reduces progression of coronary artery calcifications (CACs) and thoracic aortic calcifications (TACs). Methods: Patients with pre-existing CACs were randomized to continue on standard care or to additionally receive 5 mg of vitamin K1 orally thrice weekly. Hierarchically ordered primary endpoints were progression of TAC and CAC in computed tomography scans at 18 months. Linear mixed effects models with repeated measures at baseline and 12 and 18 months assessed treatment effects after adjusting for study site. Results: Of 60 randomized patients, 20 dropped out for reasons unrelated to vitamin K1, resulting in 23 control and 17 vitamin K1 patients. The trial was stopped early due to slow recruitment. At 18 months, the average TAC progression was 56% lower in the vitamin K1 compared with the control group (p = .039). CAC significantly progressed within the control group, but not within the vitamin K1 group. Average progression at 18 months was 68% lower in the vitamin K1 compared to the control group (P = .072). Vitamin K1 reduced plasma levels of pro-calcific uncarboxylated MGP by 69% at 18 months. No treatment-related adverse events were noted. Conclusion: Vitamin K1 intervention is a potent, safe and cost-effective approach to correct vitamin K deficiency and to potentially reduce cardiovascular calcification in this high-risk population.

Treating hyperphosphatemia - current and advancing drugs.

INTRODUCTION: Hyperphosphatemia is a hallmark of advanced chronic kidney disease (CKD) and associated with adverse outcomes. Preclinical and epidemiological studies strongly support a causal relationship between hyperphosphatemia and mortality as well as cardiovascular complications, especially including vascular, valvular and soft-tissue calcifications. Thus, appropriate phosphate lowering is considered to play a major role in health and longevity of CKD patients. In this respect, phosphate binders are the most powerful therapeutic option, while dietary phosphate restriction and intensified dialysis are valuable supportive approaches. AREAS COVERED: Pubmed was the primary research platform. This search focused on novel phosphate lowering compounds, including iron-containing binders and phosphate transport inhibitors, which have just become available or are in the approval process. Further, additional reports on effective strategies to counteract the adverse consequences of resistant hyperphosphatemia were also collected. EXPERT OPINION: New iron-containing drugs may offer advantages, including iron supplementation, low pill burden and high efficacy. Phosphate transport inhibitors possess a high potential as add-on compounds in patients with insufficient phosphate binder therapy. One unsolved question remains at what CKD stage to start therapeutically counteracting phosphate retention.

A systematic review of the effect of the Excebrane dialyser on biomarkers of lipid peroxidation.

BACKGROUND: Oxidative stress is prevalent in dialysis patients and has been implicated in the pathogenesis of cardiovascular disease and anaemia. We conducted a systematic review and meta-analysis to examine the effect of Excebrane, a vitamin E-coated cellulose-based dialyser, on circulating biomarkers of lipid peroxidation, as surrogate markers of oxidative stress. METHODS: The primary sources used to identify candidate studies included PubMed, the Cochrane Central Register of Controlled Trials, a bibliography provided by the dialyser manufacturer, and a manual search of abstracts from proceedings of scientific meetings and review articles. Studies were selected for analysis if their design included a comparator group (primarily within patient comparison, i.e. pre- and post-study evaluations). For the meta-analysis, we computed the overall change of the outcome from baseline using a random-effects model. A supplemental analysis was performed in which the absolute levels of these biomarkers of lipid peroxidation were converted to a common unit by calculating standardized effect sizes. RESULTS: Fourteen peer-reviewed articles met the criteria. The studies consisted of 11 single arm, one randomized crossover and two randomized controlled trials, with a total of 37 to 158 evaluable patients, according to the outcome of interest analysed. Due to the paucity of randomized trials, the meta-analysis was limited to the Excebrane arm of each study. When the studies were combined according to similar measurement units, the overall mean decrease in malondialdehyde (MDA) level was -0.3 mM (95% CI, -0.5 to -0.1 mM; seven studies) and -0.8 nmol/mg low-density lipoprotein (LDL) (95% CI, -1.3 to -0.4 nmol/mg LDL; three studies), respectively. The summary estimate revealed a non-significant decrease in pre-dialysis thiobarbituric acid reactive substances (TBARS) level of 0.4 microM (95% CI, -1.2 to 0.4 microM; three studies). When the MDA and TBARS studies were combined using the standardized effect size, the mean decrease in these biomarkers of lipid peroxidation was statistically significant at -1.7 units (95% CI, -2.7, -0.7 units; 13 studies). A meta-analysis on the effect of Excebrane on pre-dialysis levels of oxidized-LDL could not be performed due to study heterogeneity. CONCLUSION: The conversion of dialysis patients to a vitamin E-coated dialyser is associated with an improvement in circulating biomarkers of lipid peroxidation, which is of potential clinical benefit.