vitamin-k-semiquinone-radical and Acute-Kidney-Injury

Direct oral anticoagulants (DOACs) are variably eliminated by the kidneys rendering their use potentially problematic in patients with chronic kidney disease (CKD) or necessitating appropriate dose adjustment.. Both observational and limited randomized trial data for DOACs compared with no treatment or with warfarin for patients with atrial fibrillation on maintenance dialysis were recently published. In a randomized trial in patients on hemodialysis, there was no significant difference in vascular calcification between patients who received rivaroxaban with or without vitamin K2 or vitamin K antagonists. A randomized trial of apixaban versus warfarin was terminated owing to poor enrollment and preliminary results identified no difference in clinical outcomes between groups. However, valuable pharmacodynamic data will be forthcoming from that trial. In observational research, among patients newly diagnosed with atrial fibrillation, there were opposing trends in the associations of apixaban initiation versus no oral anticoagulation with ischemic versus hemorrhagic stroke and no association was present with the overall risk of stroke or embolism. In another study comparing apixaban with warfarin initiation, apixaban was associated with less bleeding. Regular-dose apixaban (5 mg twice daily) associated with reduced rates of ischemic stroke or systemic embolism, whereas no such association was present for those prescribed the reduced dose (2.5 mg twice daily).. DOACs may be used after appropriate dose adjustment for an established clinical indication in patients with advanced CKD. Quality evidence for oral anticoagulation, with any specific agent or dose, for stroke prevention in hemodialysis continues to be lacking.

Topics: Acute Kidney Injury; Administration, Oral; Anticoagulants; Atrial Fibrillation; Glomerular Filtration Rate; Humans; Renal Insufficiency, Chronic; Stroke; Vitamin K

As chronic kidney disease (CKD) is a contraindication to the use of the new anticoagulants, the vitamin K antagonists (VKA) are still valid in patients with CKD, though their use may be harmful. During overanticoagulation, some patients can develop acute kidney injury (AKI), especially those with CKD, by obstruction of the renal tubules and Bowman's spaces by erythrocytes. In addition, VKA increase atherogenesis through vitamin K deficiency, which is essential for the carboxylation of proteins that inhibit calcification of vessels. Eventually, hemodialysed patients under VKA have an increased risk of stroke, especially those over 75 years of age. Therefore anticoagulation with VKA in patients with CKD should be carefully implemented and its monitoring more frequent than in non-CKD patients.

Topics: 4-Hydroxycoumarins; Acute Kidney Injury; Anticoagulants; Atherosclerosis; Blood Coagulation Disorders; Cerebrovascular Disorders; Coumarins; Humans; Indenes; Renal Insufficiency, Chronic; Vitamin K; Warfarin

Vitamin K antagonists (VKAs) are still in use for oral anticoagulation, but not all indications allow their replacement by direct oral anticoagulants. Although formal dose reduction is not required in patients with impaired kidney function, case reports indicate that acute kidney injury (AKI) might be associated with derailment of VKA therapy.. The study retrospectively collected patients from a tertiary nephrology care centre who experienced AKI while being treated with VKA. In these individuals, the international normalized ratio (INR) as a measure of anticoagulant effect during renal failure was compared with a reference time point with stable kidney function.. A total of 100 patients with AKI and ongoing VKA therapy met the inclusion criteria. The majority (76%) of patients had AKI with CKD. Volume depletion (n = 43), septic renal failure (n = 22), decompensated heart failure (n = 18) and toxic renal damage (n = 11) were the most important causes of AKI. The average INR values at the time of AKI were higher than at the reference time point [median 3.17 (range 1.10-13.0) versus 2.24 (1.07-5.17); P < 0.0001]. Fifty-four patients had INR values above the recommended therapeutic range for their indication at the time point of AKI. Bleeding complications occurred in 24 patients during AKI and the VKA dose had to be reduced in 55. Women, patients with low body mass index and patients with diabetes were predisposed to overanticoagulation during AKI.. The effect of AKI on anticoagulation by VKA has not been systematically described. This risk should be considered in patients at high risk for AKI.

Topics: Acute Kidney Injury; Anticoagulants; Atrial Fibrillation; Female; Fibrinolytic Agents; Humans; International Normalized Ratio; Male; Retrospective Studies; Vitamin K

Anticoagulant-related nephropathy (ARN), a significant but frequently undiagnosed problem in patients receiving anticoagulation, is found to be associated with increased renal morbidity and all-cause mortality. While ARN is mainly associated with warfarin use, recent case reports suggest that it may also occur in patients taking direct oral anticoagulants (DOAC). We report a patient who had a history of alcoholic liver cirrhosis and paroxysmal atrial fibrillation, and received dabigatran 110 mg twice daily for 1 year. He presented with gross hematuria and severe acute kidney injury with an international normalized ratio of 4.09. Dabigatran was stopped and he was put on temporary hemodialysis support. His renal function gradually improved when the hematuria subsided. Renal biopsy later confirmed the presence of red blood cell casts inside the renal tubules with features of IgA nephropathy. Finally, his renal function returned back to baseline level. As DOAC has been increasingly used nowadays for the treatment of various thromboembolic diatheses, regular monitoring of renal function is warranted, especially in patients with underlying glomerular diseases and coagulopathy such as chronic liver diseases.

Topics: Acute Kidney Injury; Administration, Intravenous; Antifibrinolytic Agents; Antithrombins; Dabigatran; Humans; Kidney Tubules; Liver Cirrhosis; Male; Middle Aged; Necrosis; Severity of Illness Index; Treatment Outcome; Vitamin K

Topics: Acute Kidney Injury; Aged; Anti-Inflammatory Agents; Antifibrinolytic Agents; Diagnosis, Differential; Disease Progression; Hematuria; Humans; Male; Methylprednisolone; Practice Guidelines as Topic; Thrombocytopenia; Vitamin K

Among the vitamin K antagonists (VKA), indanedione-derived VKA is suspected to induce an immunoallergic risk. One indanedione-derived VKA, fluindione, is still being used in France. The aim of this study was to evaluate the contribution of VKA to acute and chronic nephritis.. Twenty-four cases of biopsy proven acute interstitial nephritis (AIN) were retrospectively selected, based on a first intake of VKA within the previous 12 months as well as an increase of at least 50% of the basal level of serum creatinine. The 24 cases were all treated with fluindione VKA and not with coumarinic VKA.. The subjects studied included 20 men and 4 women, with a mean age of 73.0±9.3 years (range: 44-84). The delay between fluindione introduction and the appearance of an AIN, proven by biopsy when available, was 11.9±6.9 weeks (range: 3-28). Creatinine increased from 123.0±56.4 μmol/L (range: 56-335) at fluindione introduction to 460.7±265.3 μmol/L (range: 109-1200) at the time of AIN discovery. The treatment then consisted of stopping the fluindione and introducing steroids for 21 patients. If a VKA was necessary, fluindione was replaced by a coumarinic VKA. After 6 months, 1 patient died and 15 patients presented severe chronic kidney disease (CKD Stages 4-5). Two patients still required chronic dialysis after 6 months and five patients after 3 years. Patients with pre-existing kidney disease were more prone to develop severe CKD with fluindione.. In this large study, arguments are presented to incriminate fluindione in the induction of acute and chronic nephritis.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anticoagulants; Coumarins; Drug Hypersensitivity; Female; Follow-Up Studies; France; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nephritis, Interstitial; Phenindione; Prognosis; Retrospective Studies; Vitamin K

We previously reported that patients with chronic kidney disease (CKD) receiving warfarin therapy and whose international normalized ratio increases to >3.0 may develop acute kidney injury (AKI) as a result of glomerular hemorrhage and formation of obstructive red blood cell (RBC) casts. We named this condition warfarin-related nephropathy (WRN). We also previously reported that acute excessive anticoagulation with brodifacoum (superwarfarin) induces AKI in 5/6 nephrectomy (5/6NE) rats. Limitations of the brodifacoum model precluded a careful assessment of dose-response relationships.. Warfarin treatment was used in 5/6NE.. Herein we report that warfarin treatment of 5/6NE rats resulted in a dose-dependent increase in serum creatinine (SC). The increase in SC following warfarin treatment was greater at 3 and 19 weeks after the ablative surgery, than that observed 8 weeks after the ablative surgery. The SC increase was correlated with the prothrombin time increase. Morphologically, 5/6NE, but not control rats, had acute tubular injury with RBC and RBC casts in the tubules. Treatment with vitamin K prevented SC increase and morphologic changes in the kidney associated with warfarin treatment. A single episode of WRN did not affect the progression of CKD in 5/6NE.. (1) The 5/6NE model of CKD is an appropriate animal model to study the pathogenesis of WRN. (2) The pharmacokinetics of warfarin is better suited to the study of WRN than that of brodifacoum. (3) The more advanced stages of 5/6NE are more susceptible to WRN than the earlier stages. (4) Vitamin K treatment prevents WRN.

Topics: Acute Kidney Injury; Analysis of Variance; Animals; Antifibrinolytic Agents; Creatinine; Humans; International Normalized Ratio; Male; Models, Animal; Nephrectomy; Prothrombin Time; Rats; Rats, Sprague-Dawley; Vitamin K; Warfarin

Acute interstitial nephritis is a frequent cause of acute renal failure, representing about 10% of all biopsied cases. Early recognition of drug-induced acute immunoallergic interstitial nephritis prevents the development of severe chronic renal injury. The list of imputable drugs includes phenindione, a vitamin K antagonist. Fluindione which is also an indanedione derivative is another vitamin K antagonist. We report three biopsy-proved cases of fluindione related acute interstitial nephritis with recovery of renal function after drug withdrawal and prednisone therapy.

Topics: Acute Disease; Acute Kidney Injury; Aged; Anticoagulants; Diuretics; Humans; Kidney Function Tests; Male; Nephritis, Interstitial; Phenindione; Treatment Outcome; Vitamin K

Topics: Acute Kidney Injury; Adult; Biopsy; Blood Urea Nitrogen; Creatinine; Humans; Kidney Failure, Chronic; Kidney Transplantation; Kidney Tubular Necrosis, Acute; Male; Time Factors; Urine; Vitamin K

We have previously demonstrated that administration of various benzoquinol-glutathione (GSH) conjugates to rats causes renal proximal tubular necrosis and the initial lesion appears to lie within that portion of the S3 segment within the outer stripe of the outer medulla (OSOM). The toxicity may be a consequence of oxidation of the quinol conjugate to the quinone followed by covalent binding to tissue macromolecules. We have therefore synthesized the GSH and N-acetylcysteine conjugates of 2-methyl-1,4-naphthoquinone (menadione) and 1,4-naphthoquinone. The resulting conjugates have certain similarities to the benzoquinol-GSH conjugates, but the main difference is that reaction with the thiol yields a conjugate which remains in the quinone form. 2-Methyl-3-(N-acetylcystein-S-yl)-1,4-naphthoquinone caused a dose-dependent (50-200 mumol/kg) necrosis of the proximal tubular epithelium. The lesion involved the terminal portion of the S2 segment and the S3 segment within the medullary ray. At the lower doses, that portion of the S3 segment in the outer stripe of the outer medulla displayed no evidence of necrosis. In contrast, 2-methyl-3-(glutathion-S-yl)-1,4-naphthoquinone (200 mumol/kg) caused no apparent histological alterations to the kidney. 2-(Glutathion-S-yl)-1,4-naphthoquinone and 2,3-(diglutathion-S-yl)-1,4-naphthoquinone (200 mumol/kg) were relatively weak proximal tubular toxicants and the lesion involved the S3 segment at the junction of the medullary ray and the OSOM. A possible reason(s) for the striking difference in the toxicity of the N-acetylcysteine conjugate of menadione, as opposed to the lack of toxicity of the GSH conjugate of menadione, is discussed. The basis for the localization of the lesion caused by 2-methyl-3-(N-acetylcystein-S-yl)-1,4-naphthoquinone requires further study.

Topics: Acetylcysteine; Acute Kidney Injury; Animals; Blood Urea Nitrogen; Glutathione; Kidney Cortex; Kidney Medulla; Kidney Tubular Necrosis, Acute; Kidney Tubules, Proximal; Magnetic Resonance Spectroscopy; Male; Naphthoquinones; Rats; Rats, Inbred Strains; Vitamin K

Topics: Acute Kidney Injury; Animals; Dogs; Horse Diseases; Horses; Vitamin K

Renal toxicosis attributable to vitamin K3 (menadione sodium bisulfite) was suspected in 5 young adult horses in which acute renal failure developed following parenteral administration of vitamin K3 at the manufacturers' recommended dosages. Renal disease was subsequently induced experimentally in 5 of 6 horses by administration of vitamin K3 at manufacturers' recommended dosages. Signs of renal disease in the clinical patients as well as in the horses treated experimentally included renal colic, hematuria, azotemia, and electrolyte abnormalities consistent with acute renal failure. Two clinical patients and 3 experimental horses were subsequently necropsied and found to have lesions of renal tubular nephrosis.

Topics: Acute Kidney Injury; Animals; Female; Hemostatics; Horse Diseases; Horses; Humans; Kidney Failure, Chronic; Kidney Tubular Necrosis, Acute; Male; Mice; Rats; Vitamin K; Vitamin K 3

Topics: Accidents, Home; Acute Kidney Injury; Gastric Lavage; Humans; Male; Middle Aged; Phosphates; Phosphorus; Plasma Substitutes; Vitamin K; Zinc