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).

Use of cetrorelix in the investigation of testosterone excess in a postmenopausal woman.

A 65-year-old woman presented to the endocrine clinic with increasing facial hirsutism over the past 6 months. She was noted to have excess hair on forearms, back and abdomen, along with some frontal balding. There were no abnormalities of the external genitalia, blood pressure was satisfactory and weight was stable. Biochemistry confirmed elevated testosterone (4.1 nmol/l). No abnormalities were seen on CT of abdomen and pelvis, nor by transvaginal ultrasound of the ovaries. Six months after her initial clinic visit, testosterone had increased to 6.0 nmol/l, rising to 7.3 nmol/l a few months later. Testosterone failed to suppress to low-dose dexamethasone suggesting excessive adrenal production was unlikely. Urine steroid profiling revealed no abnormality of adrenal steroid metabolites. Testosterone suppression was achieved with a rapidly-acting luteinizing-hormone-releasing hormone antagonist (cetrorelix), suggesting an ovarian source of excess production. Histology following bilateral salpingo-oophorectomy revealed a benign 6 mm diameter Leydig cell tumour in the right ovary.