Vitamin K supplementation to improve vascular stiffness in CKD:The K4Kidneys randomized controlled trial

BACKGROUND:Vascular calcification, a risk factor for cardiovascular disease, is common among patients with CKD and is an independent contributor to increased vascular stiffness and vascular risk in this patient group. Vitamin K is a cofactor for proteins involved in prevention of vascular calcification. Whether or not vitamin K supplementation could improve arterial stiffness in patients with CKD is unknown. METHODS:To determine if vitamin K supplementation might improve arterial stiffness in patients in CKD, we conducted a parallel-group, double-blind, randomized trial in participants aged 18 or older with CKD stage 3b or 4 (eGFR 15-45 ml/min per 1.73 m2). We randomly assigned participants to receive 400 μg oral vitamin K2 or matching placebo once daily for a year. The primary outcome was the adjusted between-group difference in carotid-femoral pulse wave velocity at 12 months. Secondary outcomes included augmentation index, abdominal aortic calcification, BP, physical function, and blood markers of mineral metabolism and vascular health. We also updated a recently published meta-analysis of trials to include the findings of this study. RESULTS:We included 159 randomized participants in the modified intention-to-treat analysis, with 80 allocated to receive vitamin K and 79 to receive placebo. Mean age was 66 years, 62 (39%) were female, and 87 (55%) had CKD stage 4. We found no differences in pulse wave velocity at 12 months, augmentation index at 12 months, BP, B-type natriuretic peptide, or physical function. The updated meta-analysis showed no effect of vitamin K supplementation on vascular stiffness or vascular calcification measures. CONCLUSIONS:Vitamin K2 supplementation did not improve vascular stiffness or other measures of vascular health in this trial involving individuals with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:Vitamin K therapy to improve vascular health in patients with chronic kidney disease, ISRCTN21444964 (www.isrctn.com)

CS22964-161: A Double-Lined Carbon- and s-Process-Enhanced Metal-Poor Binary Star

A detailed high-resolution spectroscopic analysis is presented for the carbon-rich low metallicity Galactic halo object CS 22964-161. We have discovered that CS 22964-161 is a double-lined spectroscopic binary, and have derived accurate orbital components for the system. From a model atmosphere analysis we show that both components are near the metal-poor main-sequence turnoff. Both stars are very enriched in carbon and in neutron-capture elements that can be created in the s-process, including lead. The primary star also possesses an abundance of lithium close to the value of the ``Spite-Plateau''. The simplest interpretation is that the binary members seen today were the recipients of these anomalous abundances from a third star that was losing mass as part of its AGB evolution. We compare the observed CS 22964-161 abundance set with nucleosynthesis predictions of AGB stars, and discuss issues of envelope stability in the observed stars under mass transfer conditions, and consider the dynamical stability of the alleged original triple star. Finally, we consider the circumstances that permit survival of lithium, whatever its origin, in the spectrum of this extraordinary system.Comment: manuscript, 7 tables, 13 figures. ApJ, in pres