phenprocoumon 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

A 20 year old, previously healthy woman presented with a four week history of progressive oedema of the legs and the eyelids and a weight gain of 10 kg.. Biochemical tests revealed a nephrotic syndrome with a protein-loss in urine of 13.6 g/24 hours and a serum-albumin of 1.2 g/dl. Serological tests showed positive response for antinuclear antibodies, anti-double-stranded-DNA antibodies and cardiolipin antibodies. Renal histology revealed a lupus-associated diffuse membranous nephropathy (WHO-type Vd).. We first started a treatment regimen with oral steroids and intravenous loop-diuretics without improvement of the nephrotic syndrome. Two weeks after initial presentation the patient developed dialysis-dependent, acute renal failure. Having excluded a renal vein-thrombosis and the transition to diffuse proliferative form of the glomerulonephritis we suggested a nephrotic etiology of the acute renal failure. We initiated cyclophosphamide pulse-therapy which led to dramatic improvement of the nephrotic syndrome after the first cycle with reduction of protein-loss to 6 g/24 hours. Concurrently renal function recovered and treatment with hemodialysis could be stopped after 3 weeks.. Acute renal failure in nephrotic syndrome has also to be considered in an acute form of a membranous lupus nephritis. Renal recovery is much better when acute renal failure is caused by nephrotic syndrome.

Topics: Acute Kidney Injury; Adult; Antibodies, Anticardiolipin; Antibodies, Antinuclear; Anticoagulants; Antirheumatic Agents; Cyclophosphamide; Diuretics; DNA; Edema; Female; Furosemide; Glucocorticoids; Humans; Kidney; Lupus Nephritis; Metolazone; Nephrotic Syndrome; Phenprocoumon; Prednisolone; Proteinuria; Renal Dialysis; Serum Albumin

Four patients with different forms of glomerulonephritis were treated with the anticoagulant heparin (Liquemin) or phenprocoumon (Marcumar). Following the results in these cases and the experiences of other research groups, which have been published in the last few years, we have tried to lay down a scheme for treatment with anticoagulants in glomerulonephritis. Such a treatment is recommended in peracute or rapid progressing glomerulonephritis, in forms of the disease of which is known that they have a poor prognosis, and in situations in which the risk of simultaneous thromboembolic complications as a result of a nephrotic syndrome represents a further argument for the use of anticoagulants.

Topics: 4-Hydroxycoumarins; Acute Kidney Injury; Adult; Creatinine; Female; Glomerulonephritis; Hematuria; Heparin; Humans; Male; Nephrotic Syndrome; Phenprocoumon; Prognosis; Proteinuria