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).

Investigating the Relationship between Cerebral Blood Flow and Cognitive Function in Hemodialysis Patients.

BACKGROUND: The immediate and longer-term effects of hemodialysis on cerebral circulation, cerebral structure, and cognitive function are poorly understood. METHODS: In a prospective observational cohort study of 97 adults (median age 59 years) receiving chronic hemodialysis, we used transcranial Doppler ultrasound to measure cerebral arterial mean flow velocity (MFV) throughout dialysis. Using a well validated neuropsychological protocol, we assessed cognitive function during and off dialysis and after 12 months of treatment. We also used brain magnetic resonance imaging (MRI) to assess atrophy, white matter hyperintensities (WMHs), and diffusion parameters, and tested correlations between MFV, cognitive scores, and changes on MRI. RESULTS: MFV declined significantly during dialysis, correlating with ultrafiltrate volumes. Percentage of decline in MFV correlated with intradialytic decline in cognitive function, including global function, executive function, and verbal fluency. At follow-up, 73 patients were available for repeat testing, 34 of whom underwent repeat MRI. In a subgroup of patients followed for 12 months of continued dialysis, percentage of decline in MFV correlated significantly with lower global and executive function and with progression of WMH burden (a marker of small vessel disease). Twelve of 15 patients who received renal transplants during follow-up had both early and follow-up off-dialysis assessments. After transplant, patients' memory (on a delayed recall test) improved significantly; increased fractional anisotropy of white matter (a measure of cerebral diffusion) in these patients correlated with improving executive function. CONCLUSIONS: Patients undergoing hemodialysis experience transient decline in cerebral blood flow, correlating with intradialytic cognitive dysfunction. Progressive cerebrovascular disease occurred in those continuing dialysis, but not in transplanted patients. Cognitive function and cerebral diffusion improved after transplant.