vitamin-k-1 and Acute-Kidney-Injury

Ferroptosis, a type of iron-dependent programmed cell death distinct from apoptosis, necroptosis, and other types of cell death, is characterized by lipid peroxidation, reactive oxygen species production, and mitochondrial dysfunction. Accumulating evidence has highlighted vital roles for ferroptosis in multiple diseases, including acute kidney injury. Therefore, ferroptosis has become a major focus for translational research. However, despite its involvement in pathological conditions, there are no pharmacologic inhibitors of ferroptosis in clinical use. In the context of drug repurposing, a strategy for identifying new uses for approved drugs outside the original medical application, we discovered that vitamin K1 is an efficient inhibitor of ferroptosis. Our findings are strengthened by the fact that the vitamin K antagonist phenprocoumon significantly exacerbated ferroptotic cell death in vitro and also massively worsened the course of acute kidney injury in vivo, which is of utmost clinical importance. We therefore assign vitamin K1 a novel role in preventing ferroptotic cell death in acute tubular necrosis during acute kidney injury. Since the safety, tolerability, pharmacokinetics, and pharmacodynamics of vitamin K1 formulations are well documented, this drug is primed for clinical application, and provides a new strategy for pharmacological control of ferroptosis and diseases associated with this mode of cell death.

Topics: Acute Kidney Injury; Ferroptosis; Humans; Iron; Phenprocoumon; Vitamin K 1

Systematic investigations on the status of fat-soluble vitamins in patients with acute renal failure (ARF) are lacking and hence no recommendations for vitamin supply can be defined for these subjects. Thus we compared the status of fat-soluble vitamins, of transport molecules and some vitamin-dependent proteins in patients with ARF and healthy controls.. Nephrology unit of a university hospital.. Eight patients with ARF requiring hemodialysis therapy were investigated and 28 healthy volunteers served as controls. Plasma concentrations of retinol (vitamin A) and retinol-binding protein (RBP), 25-OH and 1,25-(OH)2 vitamin D3, of parathyroid hormone (PTH), of alpha-tocopherol (vitamin E) and of phylloquinone (vitamin K), osteocalcin and noncarboxylated osteocalcin, respectively, were measured and plasma lipoprotein fractions (as vitamin transport vehicle) were evaluated.. Vitamin A levels were decreased (p < 0.001), but RBP levels were normal in ARF patients. Vitamin D3 metabolites 25-OH and 1,25-(OH)2 vitamin D3 plasma levels were profoundly depressed, and PTH was elevated (p < 0.001). Vitamin E plasma concentration was reduced (p < 0.001) but this cannot be accounted for by decreased LDL cholesterol or triglyceride levels. In contrast, vitamin K plasma level was rather elevated in ARF patients with a broad range of individual values. Blood coagulation was normal but total and carboxylated osteocalcin were decreased. No correlation of vitamin K concentrations and any of the plasma lipoprotein fractions could be identified.. With the exception of vitamin K, profound deficiencies of fat-soluble vitamins develop in patients with ARF. Current recommendations for vitamin supplementation are inadequate and should be reevaluated for these patients.

Topics: Acute Kidney Injury; Adult; Aged; Calcifediol; Calcitriol; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Male; Middle Aged; Nutritional Status; Osteocalcin; Parathyroid Hormone; Renal Dialysis; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Vitamin A; Vitamin E; Vitamin K 1; Vitamins