warfarin and Kidney-Diseases

Warfarin has been utilized for decades as an effective anticoagulant in patients with a history of strong risk factors for venous thromboembolism (VTE). Established adverse effects include bleeding, skin necrosis, teratogenicity during pregnancy, cholesterol embolization, and nephropathy. One of the lesser-known long-term side effects of warfarin is an increase in systemic arterial calcification. This is significant due to the association between vascular calcification and cardiovascular morbidity and mortality. Direct oral anticoagulants (DOACs) have gained prominence in recent years, as they require less frequent monitoring and have a superior side effect profile to warfarin, specifically in relation to major bleeding. The cost and lack of data for DOACs in some disease processes have precluded universal use. Within the last four years, retrospective cohort studies, observational studies, and randomized trials have shown, through different imaging modalities, that multiple DOACs are associated with slower progression of vascular calcification than warfarin. This review highlights the pathophysiology and mechanisms behind vascular calcification due to warfarin and compares the effect of warfarin and DOACs on systemic vasculature.

Topics: Administration, Oral; Animals; Anticoagulants; Humans; Kidney Diseases; Vascular Calcification; Warfarin

Although highly effective, warfarin use is complicated by its unpredictable narrow therapeutic window, genetic heterogeneity in pharmacokinetic response, numerous food and drug interactions, and the need for regular international normalized ratio (INR) monitoring. Currently, several novel oral anticoagulant (NOAC) drugs (dabigatran, rivaroxaban, apixaban) are available on the market as alternatives to warfarin. These agents all feature more predictable pharmacodynamic and pharmacokinetic properties than warfarin. Additionally, the NOACs do not require routine monitoring of coagulation parameters, and have a relatively lower potential for interactions with drug, herb, and dietary constituents, which enhances the convenience of management for both patients and health professionals alike. However, there are other considerations regarding the use of NOACs that must be taken into account during management of therapy. In contrast to warfarin, most NOACs need dosage adjustments in renal impairment and are contraindicated in severe liver impairment, and there are no specific antidotes for treating NOAC-related over-anticoagulation. The more frequent dosing needed for NOACs may reduce adherence, especially in elderly patients with polypharmacy. Furthermore, NOACs, especially dabigatran, are not as well tolerated as warfarin in patients with gastrointestinal diseases. Overall, the availability of the NOACs has expanded the treatment armamentarium, but they are not without risk. Given the limited experience with the NOACs, their limited range of indications, and their cost, the characteristics of each anticoagulant must be carefully considered to carefully select the agent that will provide the optimal risk/benefit profile in the individual patient.

Topics: Administration, Oral; Aging; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Complementary Therapies; Dabigatran; Drug Interactions; Drug Monitoring; Humans; International Normalized Ratio; Kidney Diseases; Liver Diseases; Morpholines; Pyrazoles; Pyridones; Rivaroxaban; Sex Factors; Stroke; Thiophenes; Warfarin

Antiphospholipid syndrome (APS) is an autoimmune disease defined by the presence of arterial or venous thrombotic events and/or pregnancy morbidity in patients who test positive for antiphospholipid antibodies (aPLs). APS can be isolated (known as primary APS) or associated with other autoimmune diseases, such as systemic lupus erythematosus (SLE; known as secondary APS). The kidney is a major target organ in APS and renal thrombosis can occur at any level within the vasculature of the kidney (renal arteries, intrarenal arteries, glomerular capillaries and renal veins); events reflect the site and size of the involved vessels. Histological findings vary widely, including ischaemic glomeruli and thrombotic lesions without glomerular or arterial immune deposits on immunofluorescence. Renal prognosis is affected by the presence of aPLs in patients with lupus nephritis and can be poor. In patients with SLE and aPLs, biopsy should be performed because inflammatory and thrombotic lesions require different therapeutic approaches. Renal involvement in patients with definite APS is treated by anticoagulation with long-term warfarin. The range of renal manifestations associated with APS is broadening and, therefore, aPLs have increasing relevance in end-stage renal disease, transplantation and pregnancy.

Topics: Adult; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Female; Humans; Infarction; Kidney; Kidney Diseases; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Lupus Nephritis; Middle Aged; Pregnancy; Renal Veins; Thrombosis; Warfarin

Topics: Animals; Anticoagulants; Humans; Kidney Diseases; Prevalence; Prognosis; Risk Factors; Warfarin

Warfarin is commonly used to prevent stroke in patients with atrial fibrillation; however, patients on haemodialysis may not derive the same benefit from warfarin as the general population. There are no randomized controlled studies in dialysis patients which demonstrate the efficacy of warfarin in preventing stroke. In fact, warfarin places the dialysis patient at increased risk for haemorrhagic stroke and possibly ischaemic stroke. Additionally, warfarin increases the risk of major bleeding and has been associated with vascular calcification. Routine use of warfarin in dialysis for stroke prevention should be discouraged, and therapy should only be reserved for dialysis patients at high risk for thrombo-embolic stroke and carefully monitored if implemented.

Topics: Anticoagulants; Atrial Fibrillation; Chronic Disease; Hemorrhage; Humans; Kidney Diseases; Renal Dialysis; Risk Factors; Stroke; Warfarin

This is a review of stroke mechanisms and management. The concept of stroke and transient ischemic attack and the recently proposed revision in definitions and controversies are discussed. We also discuss the use of antiplatelet and anticoagulant drugs for stroke due to carotid and cardiac disease.

Topics: Anticoagulants; Chronic Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypertension; Kidney Diseases; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Warfarin

Topics: Anticoagulants; Dipyridamole; Fibrin; Humans; Kidney Diseases; Platelet Activation; Platelet Aggregation Inhibitors; Receptor, PAR-1; Receptor, PAR-2; Signal Transduction; Thrombophilia; Warfarin

The use of complementary and alternative medicine (CAM) in the United States is growing at a remarkable speed. Herbal products and dietary supplements are CAM therapies that have grown faster than any other CAM treatments. Little information is available about herbs and dietary supplement use in the stage 5 chronic kidney disease population. These products contain a myriad of pharmacologically active compounds that, when used by people with kidney disease, may be hazardous. Members of the renal dietitian listserv were queried about herbs and dietary supplements reportedly used by dialysis patients. Up-to-date information on the use, safety, efficacy, adverse effects, and recommended dosages in the nondialysis population are presented for 24 products. In the dialysis population, Noni juice should be avoided because of its high potassium content. In addition, bulk-forming laxatives such as flaxseed should be used with caution because of the need for increased fluid intake. Dialysis practitioners should include specific questions about herbs and dietary supplement use in medical and nutrition histories, and they should increase their knowledge about these products to advise patients appropriately. A list of reliable sources of information for the health care provider on herbs and dietary supplements is also presented.

Topics: Complementary Therapies; Dietary Supplements; Herb-Drug Interactions; Humans; Kidney Diseases; Phytotherapy; Warfarin

The product of growth arrest-specific gene 6 (Gas6) is a unique vitamin K-dependent autocrine growth factor for mesangial cells, and warfarin inhibits mesangial cell proliferation by interfering with the activation process of Gas6. A recent series of studies has revealed the in vivo roles of Gas6 and its receptor Axl in the progression of acute and chronic glomerulonephritis, diabetic nephropathy, chronic allograft rejection, and human kidney diseases. This review summarizes these studies and discusses the possible interventions targeting the Gas6/Axl pathway to prevent the progression of kidney diseases.

Topics: Animals; Diabetic Nephropathies; DNA-Binding Proteins; Glomerular Mesangium; Glomerulonephritis; Graft Rejection; Humans; Intercellular Signaling Peptides and Proteins; Kidney Diseases; Mice; Mice, Knockout; Signal Transduction; STAT3 Transcription Factor; Trans-Activators; Vitamin K; Warfarin

Topics: Apazone; Bilirubin; Binding Sites; Carrier Proteins; Diazepam; Digitoxin; Fatty Acids, Nonesterified; Half-Life; Humans; Hydrogen-Ion Concentration; Indoles; Kidney Diseases; Kidney Failure, Chronic; Kinetics; Ligands; Liver; Methods; Protein Binding; Protein Conformation; Renal Dialysis; Serum Albumin; Toxins, Biological; Uremia; Warfarin

Topics: Adenosine; Antidepressive Agents; Aspirin; Blood Platelets; Complement System Proteins; Endothelium; Glomerulonephritis; Hemostasis; Heparin; Histamine H1 Antagonists; Humans; Immunity; Immunoglobulins; Indomethacin; Kidney Diseases; Meclofenamic Acid; Mopidamol; Phagocytosis; Phenylbutazone; Platelet Aggregation; Prostaglandins; Pyrimidines; Sulfinpyrazone; Tranquilizing Agents; Warfarin

The study sought to evaluate the effect of dabigatran dual therapy versus warfarin triple therapy across categories of renal function in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy with Dabigatran versus Triple Therapy with Warfarin in Patients with Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.. The RE-DUAL PCI (NCT02164864) trial of patients with atrial fibrillation undergoing percutaneous coronary intervention reported that dabigatran dual therapy (110 or 150 mg twice daily, plus clopidogrel or ticagrelor) reduced the primary endpoint of major bleeding events (MBE) or clinically relevant nonmajor bleeding events (CRNMBE) compared with warfarin triple therapy, with noninferiority in overall thromboembolic events.. Risk of a first MBE or CRNMBE and the composite of death or thromboembolic event (DTE) or unplanned revascularization were evaluated in 2,725 patients according to baseline creatinine clearance (CrCl) categories: 30 to <50, 50 to <80, and ≥80 ml/min.. Compared with warfarin, dabigatran 110 mg dual therapy reduced risk of MBE or CRNMBE across all categories of CrCl (p for interaction = 0.19). Dabigatran 150 mg dual therapy reduced risk of MBE or CRNMBE regardless of the CrCl category (p for interaction = 0.31). Risk of DTE or unplanned revascularization was similar to warfarin triple therapy for dabigatran 110 mg dual therapy across all CrCl categories. Dabigatran 150 mg dual therapy versus warfarin triple therapy had similar risk for DTE or unplanned revascularization in patients with CrCl 30 to <80 ml/min and lower risk at CrCl ≥80 ml/min (p for interaction = 0.02).. In the RE-DUAL PCI trial, dabigatran dual therapy reduced bleeding events versus warfarin triple therapy irrespective of renal function, with overall similar risks of thromboembolic events but lower risks with dabigatran 150 mg in patients with normal CrCl.

Topics: Aged; Aged, 80 and over; Antithrombins; Atrial Fibrillation; Coronary Artery Disease; Dabigatran; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors; Thromboembolism; Time Factors; Treatment Outcome; Warfarin

This article assesses the impact of renal impairment (RI) on the efficacy and safety of anticoagulation in patients with cancer-associated thrombosis from the Comparison of Acute Treatments in Cancer Hemostasis (CATCH) study (NCT01130025).. Renal function was assessed using the Modification of Diet in Renal Disease equation in patients with cancer-associated thrombosis who received either tinzaparin (175 IU/kg) once daily or warfarin for 6 months, in an open-label, randomized, multi-centre trial with blinded adjudication of outcomes. Associations between baseline RI (glomerular filtration rate [GFR] <60 mL/min/1.73m. Baseline-centralized GFR data were available for 864 patients (96% of study population). RI was found in 131 patients (15%;. RI in patients with cancer-associated thrombosis on anticoagulation was associated with a statistically significant increase in recurrent VTE and major bleeding, but no significant increase in CRB or mortality. No differences were observed between long-term tinzaparin therapy and warfarin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Drug Administration Schedule; Female; Fibrinolytic Agents; Glomerular Filtration Rate; Hemorrhage; Humans; Incidence; Kidney; Kidney Diseases; Male; Middle Aged; Neoplasms; Prospective Studies; Recurrence; Risk Assessment; Risk Factors; Time Factors; Tinzaparin; Treatment Outcome; Venous Thromboembolism; Warfarin; Young Adult

Venous thromboembolism (VTE) is a common and serious complication in patients with cancer; treatment guidelines recommend extended therapy of ≥6 months with low-molecular-weight heparin (LMWH) for treatment and prevention of recurrent VTE (rVTE) in this population. This post hoc analysis used data from the CLOT study-a phase III, randomized, open-label, controlled study (N = 676)-to compare the efficacy and safety of dalteparin, a LMWH, versus vitamin K antagonist (VKA) for prevention of rVTE in patients with cancer and renal impairment (creatinine clearance <60 ml/min). Overall, 162/676 (24 %) patients had renal impairment at baseline. Patients received subcutaneous dalteparin 200 IU/kg once daily during month 1, followed by 150 IU/kg once daily for months 2-6; or VKA once daily for 6 months, with initial overlapping subcutaneous dalteparin 200 IU/kg once daily for ≥5 days until international normalized ratio was 2.0-3.0 for 2 consecutive days. Endpoints included the rates of rVTE (primary) and bleeding events. Overall, fewer dalteparin-treated patients (2/74 [2.7 %]) experienced ≥1 adjudicated symptomatic rVTE compared with VKA-treated patients (15/88 [17.0 %]; hazard ratio = 0.15 [95 % confidence interval 0.03-0.65]; p = 0.01). Bleeding event rates for both treatments were similar (p = 0.47). In summary, compared with VKA, dalteparin significantly reduced risk of rVTE in patients with cancer and renal impairment (p = 0.01) while exhibiting a comparable safety profile. This analysis supports dosing patients with renal impairment in accordance with patients with normal renal function; however, anti-Xa monitoring could be considered to further support safety in selected patients, particularly those with very severe renal impairment.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Dalteparin; Female; Humans; Kidney Diseases; Male; Middle Aged; Neoplasms; Venous Thromboembolism; Vitamin K; Warfarin

Renal impairment confers an increased risk of stroke, bleeding, and death in patients with atrial fibrillation. Little is known about the efficacy and safety of apixaban in relation to renal function changes over time.. To evaluate changes of renal function over time and their interactions with outcomes during a median of 1.8 years of follow-up in patients with atrial fibrillation randomized to apixaban vs warfarin treatment.. The prospective, randomized, double-blind Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) clinical trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Serial creatinine measurements were available in 16 869 patients. Worsening of renal function was defined as an annual decrease in estimated glomerular filtration more than 20%. The relations between treatment, outcomes, and renal function were investigated using Cox regression models, with renal function as a time-dependent covariate.. Stroke or systemic embolism (primary outcome), major bleeding (safety outcome), and mortality were examined in relation to renal function over time estimated with both the Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration equations.. Among 16 869 patients, the median age was 70 years and 65.2% of patients were men. Worsening in estimated glomerular filtration more than 20% was observed in 2294 patients (13.6%) and was associated with older age and more cardiovascular comorbidities. The risks of stroke or systemic embolism, major bleeding, and mortality were higher in patients with worsening renal function (HR, 1.53; 95% CI, 1.17-2.01 for stroke or systemic embolism; HR, 1.56; 95% CI, 1.27-1.93 for major bleeding; and HR, 2.31; 95% CI, 1.98-2.68 for mortality). The beneficial effects of apixaban vs warfarin on rates of stroke or systemic embolism and major bleeding were consistent in patients with normal or poor renal function over time and also in those with worsening renal function.. In patients with atrial fibrillation, declining renal function was more common in elderly patients and those with cardiovascular comorbidities. Worsening renal function was associated with a higher risk of subsequent cardiovascular events and bleeding. The superior efficacy and safety of apixaban as compared with warfarin were similar in patients with normal, poor, and worsening renal function.. clinicaltrials.gov Identifier: NCT00412984.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Double-Blind Method; Female; Humans; Kidney; Kidney Diseases; Male; Prospective Studies; Pyrazoles; Pyridones; Treatment Outcome; Warfarin

The efficacy of adjusted-dose warfarin for prevention of stroke in atrial fibrillation patients with stage 3 chronic kidney disease (CKD) is unknown.. Patients with stage 3 CKD participating in the Stroke Prevention in Atrial Fibrillation 3 trials were assessed to determine the effect of warfarin anticoagulation on stroke and major hemorrhage, and whether CKD status independently contributed to stroke risk. High-risk participants (n = 1044) in the randomized trial were assigned to adjusted-dose warfarin (target international normalized ratio 2 to 3) versus aspirin (325 mg) plus fixed, low-dose warfarin (subsequently shown to be equivalent to aspirin alone). Low-risk participants (n = 892) all received 325 mg aspirin daily. The primary outcome was ischemic stroke (96%) or systemic embolism (4%).. Among the 1936 participants in the two trials, 42% (n = 805) had stage 3 CKD at entry. Considering the 1314 patients not assigned to adjusted-dose warfarin, the primary event rate was double among those with stage 3 CKD (hazard ratio 2.0, 95% CI 1.2, 3.3) versus those with a higher estimated GFR (eGFR). Among the 516 participants with stage 3 CKD included in the randomized trial, ischemic stroke/systemic embolism was reduced 76% (95% CI 42, 90; P < 0.001) by adjusted-dose warfarin compared with aspirin/low-dose warfarin; there was no difference in major hemorrhage (5 patients versus 6 patients, respectively).. Among atrial fibrillation patients participating in the Stroke Prevention in Atrial Fibrillation III trials, stage 3 CKD was associated with higher rates of ischemic stroke/systemic embolism. Adjusted-dose warfarin markedly reduced ischemic stroke/systemic embolism in high-risk atrial fibrillation patients with stage 3 CKD.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Blood Coagulation; Canada; Chi-Square Distribution; Chronic Disease; Drug Therapy, Combination; Female; Hemorrhage; Humans; International Normalized Ratio; Kaplan-Meier Estimate; Kidney Diseases; Male; Platelet Aggregation Inhibitors; Proportional Hazards Models; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke; Time Factors; Treatment Outcome; United States; Warfarin

Antiphospholipid antibody syndrome (APAS) is characterized by the presence of anticardiolipin antibodies (ACA) in association with thrombotic disorders of arterial and/or venus systems, spontaneous abortion(s) or thrombocytopenia.. In this multicenter study, 502 end-stage renal disease (ESRD) patients awaiting renal transplants were screened to determine the frequency of APAS, the potential risk associated with APAS, and strategies for therapeutic intervention. Ninety-three patients (19%) had high titers of ACA. Twenty-three patients had documented evidence of one or more of the thrombotic disorders such as lupus, frequent abortions, frequent thrombosis of arteriovenous shunts, biopsy-proven microrenal angiopathy, or thrombocytopenia and thus were diagnosed with APAS. Of these 23 patients, 11 received kidney transplants either with (4 patients) or without (7 patients), concomitant anticoagulation therapy.. All seven of the patients with APAS not treated with anticoagulation therapy lost their allografts within 1 week as a result of renal thrombosis. In contrast, three out of four transplant patients with APAS treated with anticoagulation therapy maintained their allografts for over 2 years. The fourth patient lost his graft within a week because of thrombosis. Of the remaining 70 patients with high titers of ACA but no evidence of thrombotic disorders, 37 received kidney transplants. None lost their allografts as a result of thrombosis. Our data suggest that, although 19% of our ESRD patients exhibit high titer of ACA, only 5% of the patients have APAS.. In conclusion, our data suggest that the patients with APAS are at high risk of posttransplant renal thrombosis. Anticoagulation therapy could prevent patients from posttransplant thrombosis in patients with APAS.

Topics: Antibodies, Anticardiolipin; Anticoagulants; Antiphospholipid Syndrome; Female; Graft Rejection; Graft Survival; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Male; Prevalence; Risk Factors; Thrombosis; Warfarin

Since its introduction in the United States in 1974, ibuprofen (Motrin, Upjohn) has been shown to be safe and effective for the treatment of pain, dysmenorrhea, inflammation, and fever. A careful review of pre-registration and postmarketing data from both patients and normal subjects clearly indicates ibuprofen's remarkable safety profile compared with that of aspirin and other commonly prescribed nonsteroidal anti-inflammatory agents. Continued safety can be anticipated on the basis of the past 15 years of review experience.

Topics: Anti-Inflammatory Agents; Aspirin; Blood Cell Count; Blood Coagulation Tests; Blood Proteins; Central Nervous System Diseases; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Eruptions; Drug Interactions; Drug Tolerance; Gastrointestinal Diseases; Humans; Ibuprofen; Kidney Diseases; Liver Function Tests; Warfarin

We experienced a 36-year-old man with lupus nephritis and antiphospholipid syndrome (APS) who received a donor kidney from his father. Twenty-two months after transplantation, at a time of poor adherence to immunosuppressants and warfarin, the patient developed sudden graft loss due to hemolytic uremic syndrome with rapid deterioration of renal function, thrombocytopenia, and hemolytic anemia. A kidney biopsy showed thrombotic microangiopathy (TMA) related to platelet thrombus formation; however, there was no recurrence of lupus and no findings suggestive of post-transplant rejection, so acute TMA associated with APS was thought to be the cause of the graft loss. This case highlights the importance of instructing patients with lupus nephritis to adhere to treatment with warfarin, a therapeutic drug for APS.

Topics: Adult; Antiphospholipid Syndrome; Humans; Kidney Diseases; Kidney Transplantation; Lupus Nephritis; Male; Thrombotic Microangiopathies; Warfarin

The effect of apixaban on anti-factor Xa (anti-Xa) assays and international normalized ratio (INR) complicates transitions between anticoagulant agents. When switching from apixaban to warfarin, the recommendation is to begin both a parenteral anticoagulant and warfarin at the time of the next apixaban dose and to discontinue the parenteral agent when the INR is in an acceptable range. This proves challenging in renal dysfunction, as continued presence of apixaban contributes to both a prolonged effect on the INR and continued therapeutic levels of anticoagulation.. This case describes the transition of apixaban to warfarin in a patient with acute on chronic kidney disease and recent deep vein thrombosis, utilizing chromogenic apixaban anti-Xa assays to assess the level of anticoagulation and avoid unnecessary parenteral anticoagulation.. Utilization of apixaban anti-Xa levels aided in the transition from apixaban to warfarin in a patient with chronic renal failure and avoided need for parenteral bridging therapy.

Topics: Anticoagulants; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; Kidney Diseases; Male; Pyrazoles; Pyridones; Warfarin

Performing percutaneous renal biopsy procedures in lupus nephritis (LN) and nephrotic syndrome presents a unique challenge to the nephrologist because of the risk of bleeding from the procedure and the hypercoagulable state in hypoalbuminemia. The management of a patient with venous thrombosis with perinephric hematoma post renal biopsy can be difficult if occurred.. We are presenting a case of perinephric hematoma following percutaneous renal biopsy in a 23-year-old man with lupus nephritis, nephrotic syndrome, and lower limbs deep vein thrombosis (DVT). The patient developed persistent frank haematuria, flank pain and acute urinary retention post-procedure. We have withheld his oral warfarin three days before the procedure, and no anticoagulation was given subsequently. Initial CT Angiography (CTA) renal showing stable hematoma and no visible evidence of vascular injury. Three weeks later, the patient still has persistent frank haematuria and a repeated CTA renal revealed new bilateral renal vein thrombosis. Considering the high risk of worsening symptomatic venous thrombosis, we gave subcutaneous enoxaparin sodium and restart oral warfarin despite ongoing haematuria. The frank haematuria resolved within two days of anticoagulation with no radiological evidence of worsening of the perinephric hematoma. The follow-up ultrasonography a month later showed resolution of the hematoma and renal vein thrombosis with no adverse effect.. Our experience, in this case, highlighted the importance of case selection for percutaneous renal biopsy among high-risk patients. Additionally, a prolonged frank haematuria in post-renal biopsy with nephrotic syndrome warranted a reassessment, as a clinical presentation of post-procedure perinephric hematoma and renal vein thrombosis can overlap. We also demonstrated that restarting anticoagulation earlier than four weeks in a patient with renal vein thrombosis and post-renal biopsy perinephric hematoma can be safe in the selective case.

Topics: Adult; Biopsy; Enoxaparin; Gastrointestinal Hemorrhage; Hematoma; Hematuria; Humans; Kidney Diseases; Lupus Nephritis; Male; Nephrotic Syndrome; Renal Veins; Ureteral Diseases; Venous Thrombosis; Warfarin; Young Adult

The use of direct oral anticoagulants for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) is robust. However, the efficacy and safety of different dosage in patients with renal dysfunction is still a clinical challenge. We aimed to evaluate the clinical characteristics and outcomes of patients treated with apixaban in its different doses. A multicenter prospective cohort study, where consecutive eligible apixaban or warfarin treated patients with NVAF and renal impairment, were registered. Patients were followed-up for clinical events over a mean period of 1 year. Analyses were performed according to the dose of apixaban given, with consideration to the standard indications for dose reduction. Primary outcome was a composite of 1-year mortality, stroke or systemic embolism, major bleeding and myocardial infarction, while secondary outcomes included those components separated. Among the study population (n = 2,140), risk of composite outcome was significantly lower in the high dose apixaban group (10%, n = 491) than the low dose group (18%, n = 673) and the warfarin group (18%, n = 976) p <0.001. Results of 1-year mortality were similar. Apixaban dosing analysis revealed 65% of patients were appropriately dosed, while 31% were under-dosed and 4% were over-dosed. Furthermore, 53% of patients treated with low dose apixaban were under-dosed. Propensity score analysis revealed that patients who were appropriately treated with low-dose apixaban had a trend towards better composite outcome and mortality than 1:1 matched warfarin treated patients (18% vs 24%, p = 0.09 and 16% vs 23%, p = 0.06, respectively). Overall, appropriately dosed apixaban treated patients at any dose had significantly better outcomes than matched warfarin treated patients (composite outcome probability of 13.1% vs 18.6%, p = 0.007). In conclusion, apixaban at any dose is a reasonable alternative to warfarin in patients with renal impairment, possibly associated with improved outcomes.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Female; Humans; Israel; Kidney Diseases; Male; Prospective Studies; Pyrazoles; Pyridones; Registries; Stroke; Warfarin

A 34-year-old Japanese woman with systemic lupus erythematosus (SLE) was admitted to our hospital for exacerbation of renal dysfunction, hemolytic anemia and thrombocytopenia. Twenty-two years before admission, she was diagnosed with SLE. Eight years before, lupus anticoagulant (LAC) positivity was detected without any thrombotic findings. Fourteen months before, renal function started to worsen. Three months before, unprovoked left leg swelling appeared. She was diagnosed with deep vein thrombosis (DVT) by ultrasonography. Blood examination revealed mild anemia, thrombocytopenia, and renal dysfunction. Rivaroxaban was started after which the left leg swelling subsided. When she was referred to our hospital, LAC was positive, but hypocomplementemia nor elevation of serum anti-double-stranded DNA antibodies was detected. Renal biopsy showed acute and chronic thrombotic microangiopathy (TMA) without concurrent lupus nephritis. Brain magnetic resonance imaging showed new small multiple cerebral infarcts. Antiphospholipid antibody syndrome (APS), causing renal TMA, new cerebral infarction, and DVT was diagnosed. Rivaroxaban was changed to warfarin. Two months after admission, renal impairment improved, and the complete disappearance of DVT and brain infarcts was confirmed. This case suggests that warfarin may be more effective than direct oral anticoagulants in the treatment of APS-associated renal TMA.

Topics: Adult; Antiphospholipid Syndrome; Female; Humans; Kidney Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Rivaroxaban; Thrombotic Microangiopathies; Treatment Outcome; Warfarin

Patients with nonvalvular atrial fibrillation (NVAF) and type 2 diabetes are at risk of kidney, limb, and ophthalmic complications. We evaluated the rate of these complications and death in patients with NVAF and type 2 diabetes prescribed rivaroxaban or warfarin.. We analyzed Optum de-Identified electronic health record (EHR) data from 11/2010-12/2019. We included adults with NVAF and T2D newly initiated on rivaroxaban or warfarin with ≥12 months of prior EHR activity. Patients with another indication for anticoagulation, valve disease, history of end-stage renal disease, major adverse limb events (MALE), diabetic retinopathy or pregnancy were excluded. We evaluated the incidence rate of developing a composite outcome of >40% decrease in estimated glomerular filtration incidence rate (eGFR) from baseline, eGFR < 15 mL/minute/1.73 m2, need for dialysis or kidney transplant, MALE, diabetic retinopathy or death. Overlap weighting was used to balance baseline characteristics between cohorts while preserving sample size. Hazard ratios with 95% confidence intervals were calculated using propensity score-overlap weighted Cox regression.. We included 24,912 rivaroxaban and 58,270 warfarin users. The mean ± standard deviation (SD) CHA2DS2VASc score was 4.3 ± 1.5 and modified HASBLED score was 1.5 ± 0.8. Thirty percent of rivaroxaban patients were started on 15 mg once daily, with the rest prescribed 20 mg once daily. Warfarin patients had a mean time in therapeutic range of 47 ± 28%. Patients were followed for a mean of 2.89 ± 1.95 years. Rivaroxaban was associated with a reduced hazard of the composite outcome (HR = 0.93, 95%CI = 0.91-0.95; absolute risk reduction = 1.97 events per 1000 patient-years; number needed-to-treat = 51) versus warfarin. Rivaroxaban was also associated with significant reductions in the relative hazard of > 40% decrease in eGFR from baseline (HR = 0.96), need for dialysis or renal transplant (HR = 0.81), and limb revascularization or major amputation (HR = 0.85). Death occurred at a lower incidence rate with rivaroxaban (HR = 0.92, 95%CI = 0.89-0.95).. Rivaroxaban was associated with reduced incidence rates of kidney and limb complications, and death in NVAF patients with type 2 diabetes compared to warfarin.

Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Diabetes Mellitus, Type 2; Electronic Health Records; Eye Diseases; Humans; Kidney; Kidney Diseases; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Warfarin

Topics: Atrial Appendage; Atrial Fibrillation; Humans; Kidney Diseases; Treatment Outcome; Warfarin

Amiodarone inhibits warfarin metabolism and is associated with major bleeding during warfarin therapy. Managing this drug-drug interaction (DDI) is challenging because of substantial interpatient variability in DDI magnitude. Because renal dysfunction induces changes in drug metabolism and protein binding that could alter cytochrome P450 inhibition mechanisms, we hypothesized that renal dysfunction alters the impact of the warfarin-amiodarone DDI. We tested this question in a propensity-matched cohort study of hospitalized patients with atrial fibrillation. Patients were queried from an electronic health record database. Renal function was estimated with creatinine clearance (CrCl). Warfarin response was measured with the warfarin sensitivity index (WSI), a dose-normalized international normalized ratio (INR) measure, and was modeled with multilevel mixed-effects linear regression. Time to supratherapeutic INR (> 4) was modeled using Cox regression. Propensity score matching resulted in 4,518 patients administered amiodarone and 4,518 controls. Amiodarone's effect on warfarin response varied threefold across the renal function range, increasing WSI by 36% in patients with normal renal function (CrCl 115 mL/minute), but by only 11.8% in patients with severe renal dysfunction (CrCl 15 mL/minute). Similarly, amiodarone had a strong effect in patients with normal renal function (hazard ratio (HR) 1.80; 1.23, 2.64), but a negligible effect on supratherapeutic INR hazard in patients with severe renal dysfunction (HR 1.01; 0.75, 1.37). These results suggest that renal function is a novel factor that explains substantial variability in the warfarin-amiodarone DDI. This information could inform warfarin dosage adjustment and monitoring and may have implications for the selection of oral anticoagulation agents in patients treated with amiodarone.

Topics: Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Cohort Studies; Drug Interactions; Female; Hemorrhage; Hospitalization; Humans; International Normalized Ratio; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Retrospective Studies; Warfarin

Apixaban in patients with impaired renal function is supported by limited data. Landmark clinical trials evaluating apixaban in patients with atrial fibrillation and/or acute venous thromboembolism excluded patients with creatinine clearance (CrCl) <25 mL/min. This multicenter, retrospective chart review was conducted to evaluate the safety and effectiveness of apixaban compared with warfarin in patients with CrCl <25 mL/min. Included patients were newly initiated on apixaban or warfarin for at least 45 days with a CrCl <25 mL/min. Patients were evaluated for thrombosis and bleeding outcomes 6 months following initiation of anticoagulation. The primary outcome was the time to first bleeding or thrombosis event. A total of 128 patients met inclusion criteria in the apixaban group and 733 patients in the warfarin group. Time to first bleeding or thrombosis event was significantly different between the apixaban and warfarin groups. Cox proportional hazards model was conducted to control for potential confounding factors for the primary outcome. After controlling for atrial fibrillation and coronary artery bypass grafting, risk of thrombotic and bleeding events was lower in the apixaban group (hazard ratio, 0.47; 95% confidence interval, 0.25-0.92). There was not a statistical difference between time to thrombosis (83 days vs 54 days, P = .648), rate of thrombosis (5.5% vs 10.3%, P = .08), time to bleeding (46 days vs 54 days, P = .886), or rate of bleeding (5.5% vs 10.9%, P = .06). The severity of bleeding and thrombotic events was not different between groups. Apixaban may serve as a reasonable alternative compared with warfarin in patients with severe renal dysfunction.

Topics: Anticoagulants; Female; Humans; Kidney Diseases; Pyrazoles; Pyridones; Retrospective Studies; Warfarin

Topics: Aged; Angiography; Anticoagulants; Embolization, Therapeutic; Female; Flank Pain; Hematoma; Humans; Kidney Diseases; Renal Artery; Tomography, X-Ray Computed; Ultrasonography; Warfarin

A 42-year-old woman was referred from a primary care centre for severe hypertension, stage 3A chronic kidney disease and proteinuria. This was associated with a significant obstetric history of pre-eclampsia during her previous two pregnancies. Secondary hypertension was suspected and autoimmune workup was positive for anticardiolipin IgG and lupus anticoagulant. A renal biopsy showed evidence of chronic thrombotic microangiopathy, with electron microscopy features suggestive of fibrillar glomerulonephritis. The diagnosis of antiphospholipid syndrome with antiphospholipid-associated nephropathy was made. She was started on anticoagulation with warfarin, and her hypertension was controlled with lisinopril and amlodipine with subsequent improvement in proteinuria. She remains on regular follow-up to monitor for possible development of malignancy or connective tissue disease.

Topics: Adult; Amlodipine; Anticoagulants; Antihypertensive Agents; Antiphospholipid Syndrome; Diagnosis, Differential; Drug Therapy, Combination; Female; Humans; Hypertension; Kidney Diseases; Lisinopril; Thrombotic Microangiopathies; Warfarin

Anticoagulation-related nephropathy may be a frequently overlooked diagnosis. Currently, there are no specific guidelines for the identification and management of anticoagulation-related nephropathy, but this is an urgent matter because of the increasing number of diseases and patients requiring anticoagulant treatment. This article discussed the research progress and controversial topics of anticoagulation-related nephropathy, and this disease is valued which be paid attention to.

Topics: Administration, Oral; Anticoagulants; Humans; Kidney Diseases; Warfarin

Nonvalvular atrial fibrillation (NVAF) is highly prevalent and increases the risks of cardiovascular events. In a recent subgroup analysis, treatment response was shown to vary for patients exhibiting worsening renal function (WRF) on-treatment. It is important to understand the cost-effectiveness of novel oral anticoagulant (NOAC) use in this population.. A cost-effectiveness analysis (CEA) was conducted using a Markov model to determine whether NOAC rivaroxaban treatment is cost-effective relative to warfarin in NVAF patients with on-treatment WRF. Input parameters were sourced from clinical literature including a multicenter clinical trial and subgroup analysis. We studied elderly US male patients at increased risk for stroke (CHADS. The remaining lifetime use of rivaroxaban is associated with 5.69 QALYs at a cost of $66,075 per patient, while warfarin produced 5.22 QALYs with costs of $78,504 per patient. At a willingness-to-pay (WTP) of $150,000 per QALY, incremental net monetary benefits (INMB) per patient are $83,590. In our population, treatment with warfarin was dominated by rivaroxaban in 99.4% of 10,000 simulations.. Rivaroxaban is likely a dominant treatment over warfarin in elderly US male NVAF patients exhibiting WRF, providing increased QALYs at a decreased overall cost. Application of these findings may require healthcare providers to predict which patients are likely to exhibit WRF.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cost-Benefit Analysis; Factor Xa Inhibitors; Humans; Kidney Diseases; Male; Rivaroxaban; Treatment Outcome; Warfarin

Warfarin-related nephropathy.. Warfarin.. A 31-year-old female, managed with warfarin for rheumatic heart disease with atrial fibrillation.. There were no alternative causes of nephropathy that could have caused the adverse event in this patient.. Shifting the drug from warfarin to acenocoumarol.. Difference in renal elimination between warfarin and acenocoumarol.. Clinicians should be aware of this rare adverse effect of warfarin, and acenocoumarol can be considered as an alternative therapy for this condition.. Further prospectively designed studies are needed to consider acenocoumarol as an alternative therapy in warfarin-related nephropathy.

Topics: Acenocoumarol; Adult; Anticoagulants; Atrial Fibrillation; Female; Humans; Kidney Diseases; Rheumatic Heart Disease; Warfarin

Anticoagulant therapy is indicated for management of ischemic stroke patients with nonvalvular atrial fibrillation. We retrospectively investigated how oral anticoagulants were selected for ischemic stroke patients with nonvalvular atrial fibrillation.. This study included 297 stroke patients with nonvalvular atrial fibrillation admitted to our hospital between September 2014 and December 2017, and who were subsequently transferred to other institutions or discharged home. Baseline clinical characteristics were compared between patients prescribed warfarin and those prescribed direct-acting oral anticoagulants.. In total, 280 of 297 (94.3%) patients received oral anticoagulant therapy, including 36 with warfarin, while 244 received direct oral anticoagulants. Age, percentage of heart failure, CHADS. Selection of oral anticoagulants in acute ischemic stroke patients with nonvalvular atrial fibrillation was influenced by warfarin use at admission, clinical severity at hospital discharge, and renal function.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Clinical Decision-Making; Female; Humans; Japan; Kidney; Kidney Diseases; Male; Patient Selection; Retrospective Studies; Risk Factors; Severity of Illness Index; Stroke; Treatment Outcome; Warfarin

It is unclear whether renal dysfunction affects warfarin control in patients with non-valvular atrial fibrillation (NVAF). Methods and Results: Using a dataset from the J-RHYTHM Registry, time in therapeutic range (TTR) of the international normalized ratio (INR) of prothrombin time, and creatinine clearance (CrCl) were determined in elderly patients aged ≥70 years. Target INR values were 1.6-2.6 following Japanese guidelines. Incidences of thromboembolism, major hemorrhage, and all-cause death were determined over 2 years. Of 7,406 NVAF patients enrolled in the registry, 2,782 elderly patients (mean age, 75 years) had data for CrCl measured at baseline and TTR. TTR values were lower in the lower CrCl groups (P<0.001 for trend). CrCl <30 mL/min was independently associated with TTR <65% (odds ratio, 1.49; 95% confidence interval, 1.13-1.95; P=0.004). In the multivariate analysis, TTR <65% was independently associated with thromboembolism (hazard ratio, 2.26; 95% confidence interval, 1.37-3.72; P=0.001), but CrCl was not (CrCl <30 mL/min, 1.68, 0.41-6.85, P=0.473). However, CrCl <30 mL/min and TTR <65% were independently associated with all-cause death (5.32, 1.56-18.18, P=0.008 and 1.60, 1.07-2.38, P=0.022, respectively) and the composite event (thromboembolism, major hemorrhage and all-cause death) (2.03, 1.10-3.76, P=0.024 and 1.58, 1.22-2.04, P=0.001, respectively).. Elderly NVAF patients with renal dysfunction had poor warfarin control, which was associated with higher risk of thromboembolism and all-cause death.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Creatinine; Female; Hemorrhage; Humans; International Normalized Ratio; Japan; Kidney Diseases; Male; Multivariate Analysis; Prothrombin Time; Registries; Risk; Thromboembolism; Treatment Outcome; Warfarin

Lifelong oral anticoagulation, either with warfarin or a non-vitamin K antagonist oral anticoagulant (NOAC), is indicated for stroke prevention in most patients with atrial fibrillation (AF). Emerging evidence suggests that NOACs may be associated with better renal outcomes than warfarin.. This study aimed to compare 4 oral anticoagulant agents (apixaban, dabigatran, rivaroxaban, and warfarin) for their effects on 4 renal outcomes: ≥30% decline in estimated glomerular filtration rate (eGFR), doubling of the serum creatinine level, acute kidney injury (AKI), and kidney failure.. Using a large U.S. administrative database linked to laboratory results, the authors identified 9,769 patients with nonvalvular AF who started taking an oral anticoagulant agent between October 1, 2010 and April 30, 2016. Inverse probability of treatment weighting was used to balance more than 60 baseline characteristics among patients in the 4 drug cohorts. Cox proportional hazards regression was performed in the weighted population to compare oral anticoagulant agents.. The cumulative risk at the end of 2 years for each outcome was 24.4%, 4.0%, 14.8%, and 1.7% for ≥30% decline in eGFR, doubling of serum creatinine, AKI, and kidney failure, respectively. When the 3 NOACs were pooled, they were associated with reduced risks of ≥30% decline in eGFR (hazard ratio [HR]: 0.77; 95% confidence interval [CI]: 0.66 to 0.89; p < 0.001), doubling of serum creatinine (HR: 0.62; 95% CI: 0.40 to 0.95; p = 0.03), and AKI (HR: 0.68; 95% CI: 0.58 to 0.81; p < 0.001) compared with warfarin. When comparing each NOAC with warfarin, dabigatran was associated with lower risks of ≥30% decline in eGFR and AKI; rivaroxaban was associated with lower risks of ≥30% decline in eGFR, doubling of serum creatinine, and AKI; however, apixaban did not have a statistically significant relationship with any of the renal outcomes.. Renal function decline is common among patients with AF treated with oral anticoagulant agents. NOACs, particularly dabigatran and rivaroxaban, may be associated with lower risks of adverse renal outcomes than warfarin.

Topics: Acute Kidney Injury; Aged; Anticoagulants; Atrial Fibrillation; Creatinine; Dabigatran; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; International Normalized Ratio; Kidney Diseases; Male; Middle Aged; Proportional Hazards Models; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Treatment Outcome; United States; Warfarin

Topics: Aged; Anticoagulants; Drug Substitution; Factor Xa Inhibitors; Humans; Kidney Diseases; Male; Necrosis; Rivaroxaban; Skin; Skin Diseases; Warfarin; Wound Healing

Acute renal infarction is a rare entity with varied misleading manifestations resulting in diagnostic delay, misdiagnosis, and treatment leading to renal damage.. We report the case of a 28-year-old Dalit Nepalese man who presented with sudden onset occipital headache and later developed severe left flank pain. He was diagnosed with posterior cerebral infarction with hemorrhagic transformation and a subsequent acute renal infarction with atrial fibrillation and hyperthyroid-induced cardiomyopathy. He was managed with oral anticoagulant and antithyroid drug.. A high index of suspicion of acute renal infarction is required in patients with risk factors of thrombosis presenting sudden onset flank pain.

Topics: Adrenergic beta-Antagonists; Adult; Angiography; Anticoagulants; Antithyroid Agents; Atrial Fibrillation; Carbimazole; Cardiomyopathies; Echocardiography; Humans; Hyperthyroidism; Infarction; Kidney Diseases; Male; Stroke; Tomography, X-Ray Computed; Warfarin

Few large studies have evaluated the adverse events associated with therapeutic colonoscopy for colorectal neoplasia, including bleeding and bowel perforation. Our aim was to investigate factors associated with these events, using a Japanese national inpatient database.. We extracted data from the nationwide Japan Diagnosis Procedure Combination database for patients who underwent therapeutic colonoscopy for colorectal neoplasia between 2013 and 2014. Therapeutic colonoscopy included endoscopic submucosal dissection (ESD), EMR, and polypectomy. Outcomes included bleeding, perforation, cerebro-cardiovascular events, and in-hospital death. A multivariable logistic regression model was used to evaluate factors associated with bleeding and bowel perforation.. We analyzed 345,546 patients, including 16,812 (4.9%) who underwent ESD, 219,848 (63.6%) who underwent EMR, and 108,886 (31.5%) who underwent polypectomy. The rates of bleeding, bowel perforation, cardiovascular events, cerebrovascular events, and death were 32.5, 0.47, 0.05, 0.88, and 1.32 per 1000 patients, respectively. In the multivariate analysis, a higher bleeding rate was associated with being male, comorbid diseases, ESD, tumor size ≥2 cm, and use of drugs including low-dose aspirin, thienopyridines, non-aspirin antiplatelet drugs, novel oral anticoagulants, warfarin, non-steroidal anti-inflammatory drugs (NSAIDs), and steroids. A higher bowel perforation rate was associated with being male, renal disease, ESD, tumor size ≥2 cm, and drugs including warfarin, NSAIDs, and steroids.. Although the incidence of adverse events after therapeutic colonoscopy was low, several patient-related factors were significantly associated with bleeding and bowel perforation.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Cerebrovascular Disorders; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Comorbidity; Endoscopic Mucosal Resection; Female; Gastrointestinal Hemorrhage; Hospital Mortality; Humans; Incidence; Intestinal Perforation; Japan; Kidney Diseases; Male; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Factors; Sex Factors; Steroids; Tumor Burden; Warfarin

Warfarin inhibits vitamin-K dependent proteins involved in bone mineralization and the prevention of vascular calcification (bone Gla protein BGP, matrix Gla protein MGP). In this multicenter, cross-sectional study with 3-year follow-up, data from 387 patients on hemodialysis for ≥1 year at 18 dialysis units were analyzed. Patients on warfarin treatment for > 1 year (11.9% of the population) were compared with the remaining cohort for vertebral fractures, vascular calcifications and mortality. Vertebral fractures and vascular calcifications were sought in L-L vertebral X-rays (D5 to L4). Compared with controls, warfarin-treated male patients had more vertebral fractures (77.8 vs. 57.7%, p<0.04), but not females (42.1% vs. 48.4%, p=0.6); total BGP was significantly reduced (82.35 vs. 202 µg/L, p<0.0001), with lower levels in treated men (69.5 vs. women 117.0 µg/L, p=0.03). In multivariate logistic regression analyses, the use of warfarin was associated with increased odds of aortic (OR 2.58, p<0.001) and iliac calcifications (OR 2.86, p<0.001); identified confounders were age, atrial fibrillation, angina, PPI use and total BGP. Seventy-seven patients died during a 2.7±0.5 year follow-up. In univariate Cox regression analysis, patients on warfarin had a higher risk of all-cause mortality (HR 2.42, 95% CI 1.42-4.16, p=0.001) when compared with those untreated and data adjustment for confounders attenuated but confirmed the significant warfarin-mortality link (HR: 1.97, 95% CI: 1.02-3.84, P=0.046). In hemodialysis patients, additional studies are warranted to verify the risk/benefit ratio of warfarin, which appears to be associated with significant morbidity and increased mortality.

Topics: Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Italy; Kaplan-Meier Estimate; Kidney Diseases; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Prevalence; Proportional Hazards Models; Renal Dialysis; Risk Factors; Sex Factors; Spinal Fractures; Time Factors; Vascular Calcification; Warfarin

Chronic kidney disease (CKD) affects the nonrenal clearance of drugs by modulating the functional expression of hepatic drug-metabolizing enzymes and transporters. The impact of CKD on oxidative and conjugative metabolism has been extensively studied. However, its effect on hepatic drug reduction, an important phase I drug-metabolism pathway, has not been investigated. We aimed to assess the effect of experimental CKD on hepatic reduction using warfarin as a pharmacological probe substrate. Cytosolic and microsomal cellular fractions were isolated from liver tissue harvested from five-sixths-nephrectomized and control rats (n = 10 per group). The enzyme kinetics for warfarin reduction were evaluated in both fractions, and formation of warfarin alcohols was used as an indicator of hepatic reductase activity. Selective inhibitors were employed to identify reductases involved in warfarin reduction. Gene and protein expression of reductases were determined using quantitative real-time polymerase chain reaction and Western blotting, respectively. Formation of RS/SR-warfarin alcohol was decreased by 39% (P < 0.001) and 43% (P < 0.01) in cytosol and microsomes, respectively, in CKD rats versus controls. However, RR/SS-warfarin alcohol formation was unchanged in the cytosol, and a trend toward its decreased production was observed in microsomes. Gene and protein expression of cytosolic carbonyl reductase 1 and aldo-keto reductase 1C3/18, and microsomal 11β-hydroxysteroid dehydrogenase type 1 were significantly reduced by >30% (P < 0.05) in CKD rats compared with controls. Collectively, these results suggest that the functional expression of hepatic reductases is selectively decreased in kidney disease. Our findings may explain one mechanism for altered nonrenal clearance, exposure, and response of drugs in CKD patients.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Alcohol Oxidoreductases; Aldehyde Reductase; Aldo-Keto Reductases; Animals; Cytosol; Disease Models, Animal; Kidney Diseases; Liver; Male; Microsomes, Liver; Oxidoreductases; Rats; Rats, Sprague-Dawley; Warfarin

In the kidney transplant population with atrial fibrillation (AF), evidence regarding the effectiveness and safety of warfarin treatment is lacking. We used fee-for-service Medicare claims to identify kidney transplant recipients with newly diagnosed AF from the United States Renal Data System. Warfarin use within 30 days of AF diagnosis was ascertained from Medicare Part D prescription claims (2007-11) or using a validated algorithm (1997-2011). The study end points were (i) the composite of death, stroke or gastrointestinal bleed, (ii) death and (iii) death-censored graft failure. Warfarin user and non-user groups were balanced using inverse probability of treatment weighting and hazard ratios were (HRs) estimated using Cox regression. Among 718 subjects with an indication for anticoagulation, 24% initiated warfarin treatment within 30 days of AF diagnosis. Age was the only independent correlate of warfarin use [odds ratio = 1.02 per year; 95% confidence interval (95% CI) 1.01-1.04]. In the larger cohort of 6492 patients with AF, warfarin use [(23.5%) versus non-use (76.5%)] was associated with small and non-significant reductions in the composite of death, stroke or gastrointestinal bleed (HR = 0.92; 95% CI 0.83-1.02), death (HR = 0.92; 95% CI 0.82-1.02) and death-censored graft failure (HR = 0.90; 95% CI 0.76-1.08). Our study suggests the need for clinical trials of warfarin use in the kidney transplant population with AF.

Topics: Aged; Algorithms; Anticoagulants; Atrial Fibrillation; Cohort Studies; Female; Humans; Incidence; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Prognosis; Risk Assessment; Transplant Recipients; Warfarin

The comparative safety of dabigatran versus warfarin for treatment of nonvalvular atrial fibrillation in general practice settings has not been established.. We formed new-user cohorts of propensity score-matched elderly patients enrolled in Medicare who initiated dabigatran or warfarin for treatment of nonvalvular atrial fibrillation between October 2010 and December 2012. Among 134 414 patients with 37 587 person-years of follow-up, there were 2715 primary outcome events. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were as follows: ischemic stroke, 0.80 (0.67-0.96); intracranial hemorrhage, 0.34 (0.26-0.46); major gastrointestinal bleeding, 1.28 (1.14-1.44); acute myocardial infarction, 0.92 (0.78-1.08); and death, 0.86 (0.77-0.96). In the subgroup treated with dabigatran 75 mg twice daily, there was no difference in risk compared with warfarin for any outcome except intracranial hemorrhage, in which case dabigatran risk was reduced. Most patients treated with dabigatran 75 mg twice daily appeared not to have severe renal impairment, the intended population for this dose. In the dabigatran 150-mg twice daily subgroup, the magnitude of effect for each outcome was greater than in the combined-dose analysis.. In general practice settings, dabigatran was associated with reduced risk of ischemic stroke, intracranial hemorrhage, and death and increased risk of major gastrointestinal hemorrhage compared with warfarin in elderly patients with nonvalvular atrial fibrillation. These associations were most pronounced in patients treated with dabigatran 150 mg twice daily, whereas the association of 75 mg twice daily with study outcomes was indistinguishable from warfarin except for a lower risk of intracranial hemorrhage with dabigatran.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Comorbidity; Dabigatran; Dose-Response Relationship, Drug; Follow-Up Studies; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Kidney Diseases; Medicare; Proportional Hazards Models; Retrospective Studies; Risk; Socioeconomic Factors; Stroke; Treatment Outcome; United States; Warfarin

We aimed to compare the efficacy and safety between non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in atrial fibrillation (AF) patients according to renal dysfunction.. We analysed 1319 patients who had been taken oral anticoagulants. They were classified into patients taking NOACs (n = 326) and warfarin (n = 993). Renal dysfunction was defined as the estimated glomerular filtration rate <60 mL/min by using the Chronic Kidney Disease Epidemiology Collaboration equation. The composite clinical outcomes were defined as the composite of death, hospitalization, and new-onset strokes. Safety outcomes were composed of major and minor bleeding. Subgroup analyses for clinical and safety outcomes were performed according to renal dysfunction during median 596 (506-612) follow-up days. The prevalence of renal dysfunction was similar between the two groups. The incidences of death, hospitalization, and strokes were not different between the two groups. However, the incidences of major bleeding was significantly higher in patients taking warfarin. In the subgroup analysis with renal dysfunction, the use of NOACs significantly improved the composite clinical outcomes (adjusted hazard ratio, HR, 0.30, 95% confidence interval, CI, 0.11-0.77, interaction P = 0.018) and major bleeding (adjusted HR 0.18, 95% CI 0.07-0.45, interaction P = 0.199) even after the covariate adjustment. However, in patients without renal dysfunction, there were no differences in the incidences of the composite clinical outcomes between the two groups.. The benefit of NOACs was more prominent in AF patients with renal dysfunction than without renal dysfunction. These results suggest that NOACs as the first choice oral anticoagulant in AF patients with renal dysfunction.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Causality; Comorbidity; Female; Hemorrhage; Humans; Kidney Diseases; Male; Prevalence; Republic of Korea; Retrospective Studies; Risk Factors; Survival Rate; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin

Our aim was to identify risk factors for acute gastrointestinal (GI) bleeding in patients with myocardial infarction (MI) who were prescribed clopidogrel following hospital discharge.. Data were collected retrospectively from patients treated in Veteran Affairs hospitals in Ohio, USA, from 2001 to 2008 with a primary diagnosis of MI (International Classification of Diseases, 9th Revision) and a prescription for clopidogrel filled within 48 h of discharge. Primary outcome was acute GI bleeding after discharge.. Acute GI bleeding occurred in 107 of 3218 patients. Bleeding occurred in those who were elder (66.2 vs. 62.4 years, P = 0.0002), had lower glomerular filtration rate (74 vs. 81 mL/min, P = 0.024), had filled prescription for warfarin (15.9% vs. 6.9%, P = 0.0004), diagnosed as atrial fibrillation (20.6% vs. 11.1%, P = 0.003), chronic liver (5.6% vs. 2.2%, P = 0.018) or kidney disease (29.0% vs. 19.4%, P = 0.016). A risk model and GI bleed risk score were developed and showed that patients with age >65 years, use of warfarin, the presence of chronic liver or kidney disease were at increased risk for GI bleeding.. Veterans patients of advanced age, using warfarin and with chronic liver and kidney disease may be at increased risk of GI bleeding when prescribed clopidogrel following MI. A scoring system may help to identify patients at high risk for GI bleeding.

Topics: Acute Disease; Age Factors; Aged; Anticoagulants; Chronic Disease; Clopidogrel; Female; Gastrointestinal Hemorrhage; Humans; Kaplan-Meier Estimate; Kidney Diseases; Liver Diseases; Male; Middle Aged; Myocardial Infarction; Ohio; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Assessment; Risk Factors; Ticlopidine; Veterans; Warfarin

This study aimed to report on original aortic valve reconstruction for patients on dialysis.. Aortic valve reconstruction has been performed on 404 cases from April 2007 through September 2011. Among them, 54 cases on haemodialysis were retrospectively studied. Forty-seven patients had aortic stenosis, 5 had aortic regurgitation (AR), and 2 had infective endocarditis. Mean age was 70.2 ± 8.5 years. There were 35 males and 19 females. There were 27 primary aortic valve reconstructions, 11 with CABG, 6 with ascending aortic replacement, 5 with mitral valve repair and 4 with maze. First, in the procedure, harvested pericardium was treated with 0.6% glutaraldehyde solution. After resecting the cusps, we measured the distance between commissures with original sizing instrument. Then, the pericardium was trimmed with the original template. Three cusps were sutured to each annulus.. Peak pressure gradient averaged to 66.0 ± 28.2 mmHg preoperatively, and decreased to 23.4 ± 10.7, 13.8 ± 5.5 and 13.3 ± 2.3 mmHg, 1 week, 1 year, and 3 years after the operation, respectively. No calcification was detected with echocardiographic follow-up. Recurrence of AR was not recorded with the mean follow-up of 847 days except for 1 case reoperated on for infective endocarditis 2.5 years after the operation. Three hospital deaths were recorded due to non-cardiac causes. Other patients were in good condition. There was no thromboembolic event.. Medium-term results are excellent. Since warfarin for dialysis patients becomes problematic, a postoperative warfarin-free status is desirable. Aortic valve reconstruction can provide patients with a better quality of life without warfarin.

Topics: Aged; Anticoagulants; Aortic Valve Insufficiency; Aortic Valve Stenosis; Cardiac Valve Annuloplasty; Female; Fixatives; Glutaral; Humans; Kaplan-Meier Estimate; Kidney Diseases; Male; Middle Aged; Pericardium; Recurrence; Renal Dialysis; Reoperation; Retrospective Studies; Time Factors; Tissue Fixation; Transplantation, Autologous; Treatment Outcome; Warfarin

We report a case of a 38-year-old man with bilateral suburothelial hemorrhage secondary to anticoagulation therapy. The condition is best diagnosed with the combination of nonenhanced and excretory phase computer tomography. It represents a rare, but easily overlooked, complication of coagulopathy.

Topics: Adult; Anticoagulants; Hemorrhage; Humans; Kidney Diseases; Male; Tomography, X-Ray Computed; Warfarin

In 2010, dabigatran etexilate, a direct thrombin inhibitor, was the first new oral anticoagulant to be approved for thromboembolic prophylaxis in atrial fibrillation in over 50 years. Dabigatran, unlike warfarin, has a short half-life with a rapid onset of anticoagulant effect, does not require dose adjustment or monitoring, and does not interact with food. The RE-LY trial compared two doses of dabigatran (110 and 150 mg twice daily) with adjusted dose warfarin in patients with non-valvular atrial fibrillation and at least 1 stroke risk factor. Compared with warfarin, dabigatran 150 mg twice daily was superior in reducing the risk of stroke or systemic embolism and was associated with a similar rate of major bleeding, while dabigatran 110 mg twice daily was equally effective in reducing stroke or systemic embolism and was associated with less major bleeding. Despite these favorable results, there remains disagreement regarding the optimal dose and overall safety of dabigatran in certain patient populations including the elderly and those with renal dysfunction.

Topics: Administration, Oral; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Benzimidazoles; Clinical Trials, Phase III as Topic; Dabigatran; Dose-Response Relationship, Drug; Female; Half-Life; Hemorrhage; Humans; Kidney Diseases; Male; Pyridines; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Thromboembolism; Warfarin

Topics: Humans; Kidney Diseases; Warfarin

The decision to prescribe oral anticoagulant therapy in patients with atrial fibrillation is based on an assessment of the competing risks of ischemic stroke and major bleeding, of which intracerebral hemorrhage (ICH) is the most important type. We sought to determine the comparative importance of risk factors for ischemic stroke and ICH in patients with acute stroke and atrial fibrillation with particular emphasis on risk factors common to both stroke types.. Consecutive patients with acute ischemic stroke or ICH and atrial fibrillation included in the Registry of the Canadian Stroke Network constituted the cohort. Multivariable logistic regression analysis was used to determine the association between baseline risk factors and presentation with ICH versus ischemic stroke. Risk factors included: (1) those previously reported to be risk factors for both ischemic stroke and major bleeding (particularly ICH) ("shared" risk factors, including age, alcohol, hypertension, diabetes mellitus, renal impairment, prior stroke/transient ischemic attack and preadmission dementia); and (2) other risk factors associated with either stroke subtype alone.. A total of 3197 patients presented with atrial fibrillation and acute stroke, of which 12.2% presented with ICH. Of the "shared" risk factors, age (OR, 1.19; 95% CI, 1.06-1.34 per decade) and prior stroke/transient ischemic attack (OR, 1.45; 95% CI, 1.12-1.87) were more associated with ischemic stroke than ICH, whereas a history of hypertension (OR, 0.89; 95% CI, 0.68-1.17), diabetes mellitus (OR 1.23; 95% CI, 0.92-1.64), renal impairment (OR, 1.28; 95% CI, 0.95-1.71), and alcohol intake were not more strongly associated with either stroke subtype.. Of the risk factors known to be associated with both ischemic stroke and ICH in patients with atrial fibrillation, we found that none had a stronger association with ICH. Older age was more strongly associated with ischemic stroke than ICH.

Topics: Age Factors; Aged; Alcohol Drinking; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Canada; Cerebral Hemorrhage; Data Interpretation, Statistical; Dementia; Diabetes Mellitus; Female; Humans; Hypertension; Kidney Diseases; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Recurrence; Registries; Risk Assessment; Risk Factors; Stroke; Warfarin

Topics: Humans; Kidney Diseases; Warfarin

Topics: Aged; Anticoagulants; Antifibrinolytic Agents; Hemorrhage; Humans; Kidney Diseases; Male; Rest; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Vitamin K 2; Warfarin

This study determined the changes in international normalized ratio (INR) that occur during hemodialysis (HD) treatment of patients receiving warfarin. Twenty patients were enrolled in the study (15 males, 5 females; mean age, 71 ± 7 years). We investigated changes in INR and R-isomer and S-isomer of warfarin concentrations before (pre-) and after (post-) HD. Post-HD INR levels were significantly decreased compared with pre-HD levels (P < 0.01), whereas plasma concentrations of both R-isomer and S-isomer of warfarin were significantly increased post-HD compared with pre-HD (P < 0.01). There was a negative correlation between INR changes and changes in warfarin concentration or changes in serum albumin levels during HD. Multivariate analysis revealed that change of serum albumin was the only factor that was significantly related to the change of INR (P = 0.0051, R = 0.501). We suggest that the free fraction of plasma warfarin decreased with increases in serum albumin levels because the protein-binding rate of warfarin is very high and free fractions were bound to albumin during HD sessions. The INR depletion was therefore dependent on circulating plasma volumes and serum albumin concentrations. Caution should be taken for those HD patients who have absolute indications of anticoagulation therapy with warfarin.

Topics: Aged; Anticoagulants; Blood Coagulation; Drug Monitoring; Female; Humans; International Normalized Ratio; Kidney Diseases; Male; Middle Aged; Multivariate Analysis; Plasma Volume; Protein Binding; Renal Dialysis; Serum Albumin; Serum Albumin, Human; Time Factors; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Chronic Disease; Hemorrhage; Humans; Kidney Diseases; Renal Dialysis; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Warfarin

Topics: Aged, 80 and over; Fibrinolytic Agents; Heparin; Hirudins; Humans; Kidney Diseases; Male; Recombinant Proteins; Thrombocytopenia; Time Factors; Treatment Outcome; Warfarin

An acute increase in the international normalized ratio (INR; a comparison of prothrombin time to monitor the effects of warfarin) over 3 in patients with chronic kidney disease (CKD) is often associated with an unexplained acute increase in serum creatinine (SC) and an accelerated progression of CKD. Kidney biopsy in a subset of these patients showed obstruction of the renal tubule by red blood cell casts, and this appears to be the dominant mechanism of the acute kidney injury. We termed this warfarin-related nephropathy (WRN), and previously reported cases of WRN only in patients with CKD. We now assess whether this occurs in patients without CKD, its risk factors, and consequences. In 15,258 patients who initiated warfarin therapy during a 5-year period, 4006 had an INR over 3 and SC measured at the same time; however, the large data set precluded individual patient clinical assessment. A presumptive diagnosis of WRN was made if the SC increased by over 0.3 mg/dl within 1 week after the INR exceeded 3 with no record of hemorrhage. WRN occurred in 20.5% of the entire cohort, 33.0% of the CKD cohort, and 16.5% of the no-CKD cohort. Other risk factors included age, diabetes mellitus, hypertension, and cardiovascular disease. The 1-year mortality was 31.1% with compared with 18.9% without WRN, an increased risk of 65%. Thus, WRN may be a common complication of warfarin therapy in high-risk patients and CKD doubles this risk. The mechanisms of these risks are unclear.

Topics: Biopsy; Chronic Disease; Erythrocyte Aggregation; Humans; International Normalized Ratio; Kidney Diseases; Kidney Tubules, Proximal; Mortality; Risk Factors; Warfarin

Numerous associations between chronic kidney disease (CKD) and atrial fibrillation (AF) have been reported and patients with CKD on anticoagulation therapy have an increased risk of bleeding. Currently, new anticoagulant agents are emerging in clinical practice, some of which are excreted by the kidneys. The proportion of AF patients on anticoagulant treatment with reduced renal function is, however, unknown.. Using AURICULA, a Swedish registry for anticoagulation, estimated glomerular filtration rate (eGFR) was investigated in AF patients on warfarin treatment (n = 2,603). The study group was compared with a healthy sample from the population (n = 2,261). Two different creatinine prediction equations were used for calculating eGFR: the Lund-Malmö (LM) and MDRD Study equation.. The fraction of AF patients with eGFR <30 and <45 ml/min/1.73 m(2) were 8.1% and 22.9% with the LM and 4.3% and 16.3% with the MDRD equation, respectively, and significantly higher than corresponding values in the reference population. GFR decreased with increasing age, where 11.4% and 5.6% of AF patients aged ≥ 75 years had eGFR <30 ml/min/1.73 m(2) according to the LM and MDRD equations, respectively.. Severe renal impairment is common among AF patients on anticoagulant treatment with warfarin, especially at higher ages. Monitoring of renal function should be implemented in clinical practice for AF patients treated with new anticoagulants eliminated by the kidneys.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Biomarkers; Case-Control Studies; Creatinine; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Logistic Models; Male; Middle Aged; Models, Biological; Registries; Risk Assessment; Risk Factors; Sweden; Treatment Outcome; Warfarin

Since its approval in the 1950s, warfarin has been the most often prescribed anticoagulant, with attendant risks of bleeding. Brodsky et al. describe another potential complication of warfarin therapy. Warfarin-related nephropathy (WRN) has been described in patients with chronic kidney disease and appears to accelerate the rate of progression and increase the risk of death. The interactions between warfarin and chronic kidney disease are complex, and the recognition of the potential complications is expanding.

Topics: Humans; Kidney Diseases; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Female; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Male; Warfarin

The objective of our study was to identify and describe the spectrum of CT findings in patients with coagulopathy-induced suburothelial hemorrhage involving the renal collecting system.. CT findings of suburothelial hemorrhage are often subtle and are best appreciated on unenhanced CT scans because of the high density of the hemorrhage. After contrast injection, uniformly thickened soft tissue enveloping the collecting system is suggestive of this condition. Clinical information regarding the presence of coagulopathy is essential for the radiologist to entertain this relatively rare diagnosis.

Topics: Adult; Aged; Anticoagulants; Contrast Media; Female; Hematoma; Hematuria; Hemorrhage; Humans; Iohexol; Kidney Diseases; Male; Middle Aged; Retrospective Studies; Tomography, X-Ray Computed; Warfarin

Topics: Humans; Kidney Diseases; Warfarin

The study aimed to predict effective human jejunal permeability (P(eff)) using a biophysical model based on parametrized paracellular, aqueous boundary layer, and transcellular permeabilities, and the villus-fold surface area expansion factor (k(VF)). Published human jejunal data (119 P(eff), 53 compounds) were analyzed by a regression procedure incorporating a dual-pore size paracellular model. Transcellular permeability, scaled by k(VF), was equated to that of Caco-2 at pH 6.5. The biophysical model predicted human jejunal permeability data within the experimental uncertainty. This investigation revealed several surprising predictions: (i) many molecules permeate predominantly (but not exclusively) by the paracellular route, (ii) the aqueous boundary layer thickness in the intestinal perfusion experiments is larger than expected, (iii) the mucosal surface area in awake humans is apparently nearly entirely accessible to drug absorption, and (iv) the relative "leakiness" of the human jejunum is not so different from that observed in a number of published Caco-2 studies.

Topics: Animals; Disease Models, Animal; Dogs; Humans; Jejunal Diseases; Kidney Diseases; Models, Biological; Permeability; Porosity; Regression Analysis

Although combination therapy for various cardiac conditions with dual antiplatelet therapy (aspirin and thienopyridine derivatives) and warfarin sodium has become increasingly popular, the safety and effectiveness of this aggressive treatment regimen remain unknown.. We retrospectively enrolled and analyzed 575 consecutive patients who had been implanted with drug-eluting coronary stents. The primary and secondary endpoints were major bleeding complications and major adverse cardiovascular events (MACE), respectively. At the time of discharge, 525 patients (91.3%) were prescribed with dual antiplatelet therapy, and 50 (8.7%) of them received dual antiplatelet plus anticoagulant therapy (triple therapy). The patients treated with triple therapy had a greater prevalence of comorbid conditions, including left ventricular systolic dysfunction and multi-vessel coronary disease compared to those on the dual antiplatelet regimen. During a median follow-up of 459 days, 14 (2.7%) patients receiving dual, and 9 (18.0%) receiving triple therapy reached the primary endpoint (p<0.001). These results show that warfarin use was associated with an increased risk of subsequent major bleeding. On the other hand, the incidence of MACE did not differ between the two groups (p=0.108 by the log-rank test). Multivariate analysis showed that renal impairment was an independent predictor of the risk of subsequent major bleeding in the triple therapy group.. Triple therapy increased the hemorrhagic complications in patients after percutaneous coronary intervention with drug-eluting stents, especially in patients with impaired renal function. Great caution should be taken with patients who necessitate the addition of anticoagulation therapy with warfarin to dual antiplatelet therapy.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Cardiovascular Diseases; Coronary Disease; Drug-Eluting Stents; Female; Hemorrhage; Humans; Kidney Diseases; Male; Platelet Aggregation Inhibitors; Prognosis; Pyridines; Retrospective Studies; Ventricular Dysfunction; Warfarin

A model-based approach was used to integrate data from a phase II study in order to provide a quantitative rationale for selecting the apixaban dosage regimen for a phase III trial. The exposure-response models demonstrated that an increase in daily steady-state area under the plasma concentration-vs.-time curve (AUC(ss)) of 1 microg x h/ml would increase the odds ratio for major bleeding by 0.118 and decrease the odds ratio for venous thromboembolism (VTE) by 0.0499. The therapeutic utility index (TUI) was used to integrate the efficacy and safety predictions to quantify apixaban's efficacy/safety balance as a function of AUC(ss). Of the apixaban dosage regimens tested in phase II, the 2.5 mg twice-daily (b.i.d.) dosage regimen had the highest TUI (86.2%). This was also higher than the TUI for either 30 mg b.i.d. enoxaparin (82.5%) or for warfarin (71.8%). Subjects with moderate renal impairment are expected to have a 43% increase in apixaban exposure; however, apixaban's TUI suggests that dose adjustment is not needed in these subjects with renal impairment.

Topics: Aged; Area Under Curve; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Computer Simulation; Dose-Response Relationship, Drug; Enoxaparin; Female; Fibrinolytic Agents; Hemorrhage; Humans; Kidney Diseases; Male; Models, Biological; Pyrazoles; Pyridones; Venous Thromboembolism; Warfarin

Topics: Anticoagulants; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Risk Factors; Thrombophilia; Warfarin

Atrial fibrillation (AF) substantially increases the risk of ischemic stroke, but this risk varies among individual patients with AF. Existing risk stratification schemes have limited predictive ability. Chronic kidney disease is a major cardiovascular risk factor, but whether it independently increases the risk for ischemic stroke in persons with AF is unknown.. We examined how chronic kidney disease (reduced glomerular filtration rate or proteinuria) affects the risk of thromboembolism off anticoagulation in patients with AF. We estimated glomerular filtration rate using the Modification of Diet in Renal Disease equation and proteinuria from urine dipstick results found in laboratory databases. Patient characteristics, warfarin use, and thromboembolic events were ascertained from clinical databases, with validation of thromboembolism by chart review. During 33,165 person-years off anticoagulation among 10,908 patients with AF, we observed 676 incident thromboembolic events. After adjustment for known risk factors for stroke and other confounders, proteinuria increased the risk of thromboembolism by 54% (relative risk, 1.54; 95% CI, 1.29 to 1.85), and there was a graded, increased risk of stroke associated with a progressively lower level of estimated glomerular filtration rate compared with a rate > or =60 mL x min(-1) x 1.73 m(-2): relative risk of 1.16 (95% CI, 0.95 to 1.40) for estimated glomerular filtration rate of 45 to 59 mL x min(-1) x 1.73 m(-2) and 1.39 (95% CI, 1.13 to 1.71) for estimated glomerular filtration rate <45 mL x min(-1) x 1.73 m(-2) (P=0.0082 for trend).. Chronic kidney disease increases the risk of thromboembolism in AF independently of other risk factors. Knowing the level of kidney function and the presence of proteinuria may improve risk stratification for decision making about the use of antithrombotic therapy for stroke prevention in AF.

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; California; Chronic Disease; Comorbidity; Creatinine; Female; Fibrinolytic Agents; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Proteinuria; Risk Factors; Stroke; Thromboembolism; Warfarin

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Atrial Fibrillation; Chronic Disease; Combined Modality Therapy; Disease Progression; Electric Countershock; Female; Heart Rate; Humans; Kidney Diseases; Risk Factors; Stroke; Stroke Volume; Warfarin

The role of genetic polymorphisms and genetic testing in guiding warfarin dosing is discussed, as are the selection and monitoring of anticoagulant therapy for obese patients, patients with severe renal impairment, and patients with heparin-induced thrombocytopenia (HIT); case studies are used to illustrate each topic.. Genetic polymorphisms influence metabolism of and sensitivity to warfarin. People with certain ethnic backgrounds have a greater likelihood of having genetic polymorphisms that reduce warfarin dosing requirements and increase the risk of bleeding. Genetic testing has the potential to improve patient safety; however, its cost is high, and genetic polymorphisms account for only part of interindividual variation in dosing requirements. For obese patients, dose capping of low molecular weight heparin is not warranted, and twice-daily enoxaparin is preferred over once-daily dosing. Anti-Xa monitoring is perhaps not necessary for patients weighing less than 190 kg (418 lb), but it may be useful to adjust dosing in heavier patients. In patients with severe renal impairment, bleeding during anticoagulant therapy may be attributed to the uremic state, excessive doses, or both. Dosage reduction and anti-Xa monitoring are recommended for patients with severe renal impairment. Treatment of patients with HIT should include discontinuation of heparin, temporary interruption of warfarin therapy, and initiation of a direct thrombin inhibitor.. Safe and effective use of anticoagulant therapy may require consideration of genetics, obesity, renal impairment, or the potential for HIT; selecting anticoagulant therapy on the basis of these considerations can present a challenge.

Topics: Aged; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Female; Heparin; Humans; Kidney Diseases; Male; Middle Aged; Mixed Function Oxygenases; Obesity, Morbid; Pharmacogenetics; Polymorphism, Genetic; Thrombocytopenia; Vitamin K Epoxide Reductases; Warfarin

Topics: Abscess; Adult; Anti-Bacterial Agents; Diagnosis, Differential; Drug Therapy, Combination; Dysuria; Female; Fever of Unknown Origin; Fibrinolytic Agents; Flank Pain; Humans; Kidney Diseases; Renal Veins; Thrombosis; Tomography, X-Ray Computed; Warfarin

A 53-year-old man presented to hospital 2 hours after the abrupt onset of left upper abdominal pain. He was treated with analgesics and discharged after 4 hours of observation, but presented to another hospital 2 hours later with severe left abdominal pain. His past medical history included ischemic dilated cardiomyopathy due to recurrent myocardial infarction.. Physical examination, electrocardiography, laboratory investigations, contrast-enhanced computed tomography, and transesophageal echocardiography.. Renal artery thromboembolism resulting from dilated cardiomyopathy, severely reduced cardiac function and an intracardiac thrombus.. Anticoagulation with unfractionated heparin followed by enoxaparin and warfarin.

Topics: Abdominal Pain; Acute Disease; Anticoagulants; Cardiomyopathy, Dilated; Coronary Thrombosis; Diagnosis, Differential; Echocardiography, Transesophageal; Enoxaparin; Humans; Infarction; Kidney Diseases; Male; Middle Aged; Renal Artery; Tomography, X-Ray Computed; Warfarin

To determine whether serum contains an activity that induces artery calcification.. The elastic lamellae of devitalized rat aortas calcify rapidly in rat or bovine serum, or in human serum provided [Pi] > or =2 mmol/L. This calcification is attributable to a potent serum calcification factor (SCF), one that causes devitalized aortas to calcify when incubated in DMEM containing as little as 1.5% serum but not in DMEM alone. The SCF that initiates medial elastin calcification has the same 50- to 150-kDa size and protease sensitivity as the SCF shown previously to initiate calcification of type I collagen. Our working hypothesis is that the same SCF initiates calcification of collagen and elastin, and that this SCF arises from sites of normal bone mineralization and, like alkaline phosphatase, is released into general circulation. The SCF does not initiate medial elastin calcification in living arteries, which suggests that vascular cells may prevent this calcification. This hypothesis is supported by the observations that living arteries secrete the calcification inhibitor matrix Gla protein (MGP); that inactivation of MGP with warfarin causes living arteries to calcify; and that addition of MGP to medium containing warfarin prevents this calcification.. The elastic lamellae of devitalized aortas calcify rapidly in serum.

Topics: Animals; Arteries; Calcification, Physiologic; Calcinosis; Calcium-Binding Proteins; Cattle; Extracellular Matrix Proteins; Humans; Kidney Diseases; Matrix Gla Protein; Rats; Serum; Warfarin

Coumadin-induced renal and retroperitoneal hemorrhages are rare. Clinical and laboratory findings are not specific for the diagnosis. Computed tomography (CT) has some advantages in the evaluation of these patients. The aim of this study is to report our experience regarding renal and retroperitoneal hemorrhage due to Coumadin, and describe clinical and CT findings, treatment, and prognosis of the patients.. We reviewed our CT archive to search patients with renal and retroperitoneal hemorrhage caused by Coumadin treatment retrospectively. A total of seven patients with Coumadin-induced renal and retroperitoneal hemorrhages were included in this study.. Four patients had abdominal pain, two patients had hematuria, and one patient had abdominal pain and hematuria. There was retroperitoneal hemorrhage in three patients on abdominal CT. One patient had hemorrhage in the renal pelvis and the jejunum, another had hemorrhage in the renal pelvis and the perirenal area, and another had hemorrhage in the perirenal area and the retroperitoneal region. In the last patient with hematuria, there was no hemorrhage. None of the patients had a lesion-causing hemorrhage. Coumadin was stopped, and vitamin K and fresh-frozen plasma were given to patient. One patient with massive retroperitoneal hemorrhage died, whereas other patients were successfully treated using conservative approaches.. Hematuria and abdominal pain are the most common complaints in Coumadin-induced renal and retroperitoneal hemorrhage. CT can be the first imaging modality in these patients due to its ability to directly evaluate all peritoneal and retroperitoneal structures. It also allows evaluation of any underlying lesion that can cause hemorrhage from the renal area and the urinary tract. Conservative treatment is the first choice, and prognosis is good when diagnosed early.

Topics: Adult; Aged; Anticoagulants; Female; Hemorrhage; Humans; Kidney Diseases; Male; Middle Aged; Retroperitoneal Space; Retrospective Studies; Tomography, X-Ray Computed; Warfarin

Nephropathy is one of the most common complications of diabetes mellitus. Glomerular hypertrophy is a hallmark in the early phase of the nephropathy. The mechanism of glomerular hypertrophy, however, remains incompletely understood. We have reported that Gas6 (growth arrest-specific gene 6) and its receptor, Axl, play a key role in the development of glomerulonephritis. Here we show the important role of Gas6/Axl in the pathogenesis of diabetic glomerular hypertrophy. In streptozotocin (STZ)-induced diabetic rats, mesangial and glomerular hypertrophy and an increase in the glomerular filtration rate (GFR) and albuminuria were observed after 12 weeks of STZ injection. The glomerular expression of Gas6 and Axl was increased in those rats. Administration of warfarin inhibited mesangial and glomerular hypertrophy and the increase in GFR and albuminuria in STZ rats. Moreover, we found less mesangial hypertrophy in STZ-treated Gas6 knockout mice than control mice. In vitro we found that stimulation of mesangial cells with Gas6 resulted in mesangial cell hypertrophy. Thus we have found a novel mechanism of glomerular hypertrophy through the Gas6/Axl-mediated pathway in the development of diabetic nephropathy. Inhibition of the Gas6/Axl pathway in diabetic patients might be beneficial to slow down the progression of diabetic nephropathy.

Topics: Albuminuria; Animals; Axl Receptor Tyrosine Kinase; Blotting, Western; Diabetic Nephropathies; Disease Progression; Flow Cytometry; Glomerular Filtration Rate; Humans; Hypertrophy; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Kidney; Kidney Diseases; Leucine; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Oncogene Proteins; Proteins; Proto-Oncogene Proteins; Rats; Receptor Protein-Tyrosine Kinases; Recombinant Proteins; Time Factors; Transforming Growth Factor beta; Transforming Growth Factor beta1; Warfarin

Topics: Aged; Anticoagulants; Hematoma; Humans; Kidney Diseases; Male; Tomography, X-Ray Computed; Venous Thrombosis; Warfarin

To study the demographic and clinical characteristics of patients with antiphospholipid syndrome (APS) with serious haemorrhagic complications of anticoagulant treatment in an attempt to establish risk factors for bleeding.. Patients with APS who were attending our lupus unit and who presented with severe bleeding while receiving oral anticoagulation were studied retrospectively. Severe bleeding was defined by the need for admission to hospital. Demographic data, clinical features, concomitant diseases and drugs, warfarin doses, duration of anticoagulation, and International Normalised Ratios (INR) at the time of bleeding were collected.. Fifteen patients were included in the study (12 with systemic lupus erythematosus (SLE) plus APS and 3 with primary APS). The median age was 41.7 (range 27-66) and the median duration of the disease was 12.9 years (range 3-22). Duration of anticoagulation was between 10 days and 17 years. The INR at the time of bleeding was under 3 in 4 patients, between 3 and 4 in 5 patients and above 4 in 6 patients. There were 4 episodes of subdural haematoma, 4 episodes of renal haematoma (two after renal biopsy), 2 episodes of ovarian haemorrhage, 2 episodes of rectal haemorrhage, 1 episode of menorrhagia, 1 episode of haemarthrosis, and 1 episode of spinal haematoma. Concomitant drugs were aspirin in 9 patients, antibiotics in 2 patients, and azathioprine in 3 patients. In 6 patients hypertension was present as a concomitant disease. There were no deaths due to bleeding. Anticoagulant treatment was restarted in all patients and 3 of them had a new episode of bleeding.. No relation was established between age, duration of oral anticoagulant treatment, and bleeding. Concomitant drugs, mainly aspirin, and high blood pressure were present at the time of bleeding in a large number of patients.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Female; Hemarthrosis; Hematoma; Hematoma, Subdural; Hemorrhage; Humans; Hypertension; Kidney Diseases; Male; Menorrhagia; Middle Aged; Ovarian Diseases; Recurrence; Risk Factors; Thrombosis; Warfarin

Topics: Anticoagulants; Diagnosis, Differential; Female; Hematuria; Hemorrhage; Humans; Kidney Diseases; Kidney Neoplasms; Kidney Pelvis; Middle Aged; Mucous Membrane; Radiography; Warfarin

Topics: Adult; Anticoagulants; Drug Overdose; Hemorrhage; Humans; Kidney Diseases; Male; Ureteral Diseases; Urothelium; Warfarin

Because proliferation of mesangial cells is a hallmark of glomerular diseases, understanding the regulatory mechanism of mesangial proliferation is important for the treatment. Warfarin has long been used to treat glomerular diseases, although its mechanism of effect on mesangial proliferation has remained unknown. Therefore, this study was conducted to examine whether warfarin can inhibit mouse mesangial cell proliferation by focusing on Gas6, which has been shown to be activated by vitamin K-dependent gamma-carboxylation. In mesangial cells, Gas6 and its receptor Axl were expressed. In addition, exogenous Gas6 phosphorylated Axl, activated extracellular signal-regulated kinase, and stimulated [3H]-thymidine incorporation in mouse mesangial cells. This study also examined whether endogenous Gas6 stimulates mesangial proliferation. Conditioned medium (CM) from serum-starved mesangial cells could stimulate [3H]-thymidine incorporation and phosphorylate extracellular signal-regulated kinase, whereas CM in the presence of warfarin could not. Simultaneous administration of vitamin K could cancel the inhibitory effect of warfarin. These results suggest that vitamin K-dependent growth factors in the CM are critical for mesangial proliferation. Addition of the extracellular domain of Axl to the CM inhibited its mitogenic effect on mesangial cells, suggesting that this vitamin K-dependent growth factor is Gas6. It is concluded that Gas6 is an endogenous mitogen in mesangial cells, and warfarin inhibits mesangial proliferation possibly by inhibiting gamma-carboxylation of Gas6. This study sheds light on the regulation of mesangial proliferation and may lead to a new therapeutic strategy for glomerular diseases.

Topics: Animals; Axl Receptor Tyrosine Kinase; Cell Division; Cells, Cultured; Culture Media, Conditioned; Glomerular Mesangium; Humans; Intercellular Signaling Peptides and Proteins; Kidney Diseases; Mice; Mitogen-Activated Protein Kinases; Mitogens; Oncogene Proteins; Phosphorylation; Proteins; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases; Vitamin K; Warfarin

The authors report an unusual case of acute renal failure occurring in a patient with systemic lupus erythematosus and antiphospholipid antibodies. Kidney biopsy revealed glomerular thrombosis, in the absence of glomerulonephritis. The authors stress the clinical and biological signs that suggest the thrombotic nature of kidney failure in lupus patients.

Topics: Acute Kidney Injury; Adult; Antibodies, Antiphospholipid; Anticoagulants; Biopsy; Capillaries; Female; Heparin; Humans; Kidney Diseases; Kidney Glomerulus; Lupus Erythematosus, Systemic; Thrombosis; Warfarin

A 62-year-old woman was admitted with malfunction of the Hancock valve in mitral position. She had been suffering from gastroduodenal ulcer for about ten years. She couldn't take warfarin after 5 years later of the initial operation due to recurrent gastrointestinal bleeding. Judging from her age and renal dysfunction, we preferred mechanical valve to avoid the risks for the reoperation. After confirming the healed ulcer with administering omeprazole, we performed prosthetic valve replacement with SJM 29 M successfully. Postoperative course was uneventful and recurrence of the ulcer was not observed.

Topics: Female; Heart Valve Prosthesis; Humans; Kidney Diseases; Middle Aged; Mitral Valve; Omeprazole; Peptic Ulcer; Peptic Ulcer Hemorrhage; Prosthesis Failure; Recurrence; Reoperation; Warfarin

A female patient with a history of migraines and chorea developed polyarthralgia at age 24 and was diagnosed with rheumatoid arthritis. In 1991 she was hospitalized because of impaired renal function and hypertension. Examination revealed thrombocytopenia and the presence of lupus anticoagulant. Antinuclear antibody was weakly positive, but anti-DNA antibody was negative, and no decrease in leukocyte count or complement level was observed. Rheumatoid arthritis with antiphospholipid syndrome was diagnosed. Renal biopsy showed renal thrombotic microangiopathy. This renal lesion was considered to be associated with antiphospholipid syndrome. Cyclophosphamide pulse therapy and anticoagulation therapy decreased proteinuria and improved renal function.

Topics: Adult; Antiphospholipid Syndrome; Arthritis, Rheumatoid; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Kidney; Kidney Diseases; Radiography; Thrombosis; Warfarin

Percutaneous fine-needle aspiration biopsy has gained wide acceptance due to its accuracy, ease of performance, and safety. This study was performed to evaluate the effect of needle size, coagulation impairment, or biopsy of different organs on risk of bleeding during the procedure. Multiple biopsy procedures were performed on the livers and kidneys of anesthetized pigs with 14-22-gauge Chiba-type needles. The procedures were performed under direct vision at laparotomy, and blood loss was measured. While larger needles generally produced more bleeding, the differences were statistically significant only when comparing 14- with 16-gauge needles and 16-gauge needles with the group of 18-, 20-, and 22-gauge needles in the liver. In the kidney, no significant difference was noted between 18-, 20-, and 22-gauge needles. Anticoagulation did not produce significantly greater blood loss but did allow separation of the group of 18- and 20-gauge needles from 22-gauge needles in the kidney. Renal biopsy resulted in greater overall blood loss than did liver biopsy.

Topics: Animals; Biopsy, Needle; Hemorrhage; Kidney Diseases; Liver Diseases; Needles; Reference Values; Swine; Warfarin

The effect of anticoagulation upon renal edema and plasma protein accumulation in acute ischemic renal damage was studied. Rats were subjected to unilateral renal artery occlusion for 60 min and 15 min of reflow. The kidney weight and the content of 125-I-fibrinogen and 131-I-albumin, injected 24 h priorly, were measured and the renal morphology studied. Groups of rats were pretreated with a heparin analogue with low anticoagulant effect, standard heparin, warfarin or saline. A marked increase in fibrinogen and albumin content and of the weight of the damaged kidney was noted. Heparin and warfarin both significantly attenuated these changes, whereas the heparin analogue did not. Microscopically, fibrin-positive material was seen in the peritubular capillaries, vasa recta and in the tubules of rats pretreated with saline or the heparin analogue, but not in rats pretreated with heparin or warfarin. The results support the hypothesis that fibrin deposition in the kidney is of importance for the development of renal edema in this model of ischemic renal damage.

Topics: Animals; Blood Pressure; Edema; Female; Fibrinogen; Heparin; Ischemia; Kidney; Kidney Diseases; Rats; Rats, Inbred Strains; Renal Artery; Renal Circulation; Serum Albumin; Warfarin

The development of bilateral parapelvic hemorrhagic pseudocysts with abdominal pain, systemic symptoms of malaise and fever, elevation of erythrocyte sedimentation rate and serum alkaline phosphatase, and decreased renal function is described in a patient taking anticoagulants. The symptoms and signs resolved with the resolution of the hemorrhagic pseudocysts. The bilaterality and selective localization of these hemorrhages suggest the existence of a specific pathogenesis. The advent of new imaging techniques in the last decade allows for a diagnosis and a better understanding of the pathologic processes that affect the renal sinus.

Topics: Cysts; Hemorrhage; Humans; Kidney Diseases; Kidney Pelvis; Male; Middle Aged; Tomography, X-Ray Computed; Warfarin

We describe a case of spontaneous infection of a renal hematoma complicating warfarin sodium anticoagulant therapy. The infected hematoma was successfully drained by sonar-guided fine-needle aspiration. All reported cases of renal hematomas complicating anticoagulant therapy are reviewed.

Topics: Aged; Drainage; Escherichia coli Infections; Female; Hematoma; Humans; Kidney Diseases; Warfarin

We evaluated 29 consecutive patients in whom gross or microscopic hematuria developed while they were on heparin or warfarin anticoagulant therapy. Patients who had bleeding as a result of anticoagulant overdosage and/or from an additional organ system(s) other than the urinary tract were excluded from this review. Significant pathological findings consisting of carcinoma, calculi, renal infarction, infection, benign prostatic hyperplasia and/or adult polycystic renal disease were identified in 17 patients. Insignificant or incidental pathological findings classified as posterior urethritis, simple renal cyst or renal scarring were noted in 6 patients. No pathological condition was found in the remaining 6 patients. We conclude that a thorough and appropriate evaluation of the urinary tract should be conducted in patients on anticoagulant therapy who have gross or microscopic hematuria, since a pathological lesion of variable clinical significance often is discovered.

Topics: Adult; Aged; Aged, 80 and over; Female; Hematuria; Heparin; Humans; Kidney Diseases; Male; Middle Aged; Urinary Calculi; Urologic Neoplasms; Warfarin

Topics: Azathioprine; Chlorambucil; Cyclophosphamide; Dipyridamole; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Humans; Kidney Diseases; Kidney Glomerulus; Nephritis; Nephrosis, Lipoid; Nephrotic Syndrome; Prednisone; Warfarin

Topics: Aged; Anticoagulants; Diagnosis, Differential; Female; Hematoma; Humans; Kidney Diseases; Kidney Neoplasms; Tomography, X-Ray Computed; Warfarin

Topics: Half-Life; Humans; Kidney Diseases; Kinetics; Warfarin

The serum protein binding of phenytoin, salicylic acid, sulfisoxazole, and warfarin was determined in normal human adults, in patients with impaired renal function (kidney donor and recipient), and in adult male Sprague--Dawley rats. The free fraction values for salicylate and sulfisoxazole were significantly correlated in all three groups. The other correlations were statistically significant in only one or two of these groups. There was a statistically significant negative correlation between albumin concentration and the free fraction values of salicylic acid and sulfisoxazole (but not of phenytoin and only under special circumstances with warfarin) in normal subjects and of phenytoin, salicylic acid, and sulfisoxazole (but not warfarin) in rats. No such correlation was observed for any of the drugs in patients with impaired renal function. These observations show that no single weakly acidic drug can serve as an index for quantitatively determining the effect of disease or species differences on the serum protein binding of other weakly acidic drugs.

Topics: Adolescent; Adult; Animals; Blood Proteins; Female; Humans; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Pharmaceutical Preparations; Phenytoin; Protein Binding; Rats; Salicylates; Serum Albumin; Sulfisoxazole; Time Factors; Transplantation, Homologous; Warfarin

Topics: Anticoagulants; Female; Hematoma; Hematuria; Humans; Kidney Diseases; Kidney Diseases, Cystic; Middle Aged; Warfarin

Topics: Animals; Blood Proteins; Humans; Kidney Diseases; Models, Biological; Pharmaceutical Preparations; Phenytoin; Protein Binding; Rats; Warfarin

The in vitro plasma protein binding of warfarin was evaluated by ultrafiltration in plasma from seven normal subjects and seven patients with varying degrees of renal dysfunction. The unbound, or free, warfarin fraction was twice as high in the plasma samples withdrawn from patients with renal impairment than in the samples obtained from normal volunteers. Furthermore, there was a positive correlation between the extent of renal dysfunction and the magnitude of the free warfarin fraction when either creatinine clearance, plasma creatinine, or BUN was used to estimate renal function.

Topics: Adult; Blood Proteins; Blood Urea Nitrogen; Creatinine; Female; Humans; Kidney Diseases; Male; Protein Binding; Warfarin

A case is reported in which anticoagulant therapy for thrombophlebitis and pulmonary embolism produced bilateral massive intrarenal hematomas (pseudotumors). The role of radiologic investigation (nephrotomography, renal scan and selective high dose arteriography) was found to identify and localize the intrarenal hematomata and exclude underlying renal pathology. Although an abnormal kidney is more likely to bleed, this case presentation demonstrates that even carefully monitored anticoagulation within the therapeutic range can induce massive intrarenal hemorrhage in previously normal kidneys. The renal architecture returned to normal on late follow-up examination on simple conservative management.

Topics: Female; Hematoma; Humans; Kidney; Kidney Diseases; Middle Aged; Pulmonary Embolism; Radiography; Thrombophlebitis; Warfarin

Clinical features have been correlated with renal function, histology and selective renal angiography in 19 patients with recurrent painless haematuria, recurrent loin pain, or both haematuria and loin pain in whom urinary infection, calculi and anatomical abnormalities of the urinary tract had been excluded. No deterioration in renal function was observed in any patient over periods of up to nine years. Although all patients showed similar glomerular changes histologically, consisting of focal and segmental mesangial thickening and proliferation and periglomerular fibrosis, mild tubular damage was more common in those with loin pain. All patients with loin pain whether or not they had haematuria, had abnormal renal angiograms consisting of focal or generalized vascular lesions sometimes associated with cortical infarcts. The possible aetiological factors are discussed with particular reference to oestrogen-containing compounds.

Topics: Adolescent; Adult; Biopsy; Blood Vessels; Estrogens; Female; Hematuria; Humans; Infarction; Kidney; Kidney Cortex; Kidney Diseases; Male; Pain; Radiography; Recurrence; Renal Artery; Warfarin

Topics: Aspirin; Blood Coagulation; Complement System Proteins; Diabetic Nephropathies; Dipyridamole; Fibrin; Fibrinogen; Glomerulonephritis; Hemolytic-Uremic Syndrome; Heparin; Humans; Iodine Radioisotopes; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Transplantation; Plasminogen; Proteinuria; Thrombosis; Transplantation, Homologous; Uremia; Warfarin

Topics: Anticoagulants; Female; Heparin; Humans; Kidney Diseases; Male; Middle Aged; Nephrectomy; Prothrombin Time; Rupture, Spontaneous; Warfarin

Topics: Adult; Biopsy; Creatinine; Diethylstilbestrol; Female; Humans; Kidney; Kidney Diseases; Microcirculation; Prednisone; Thrombosis; Warfarin

Topics: Antigens; Fibrin; Fibrinogen; Humans; Immunoassay; Kidney Diseases; Kidney Transplantation; Transplantation, Homologous; Urine; Warfarin

Topics: Adolescent; Anticoagulants; Child; Complement System Proteins; Female; Glomerulonephritis; Granulomatosis with Polyangiitis; Heparin; Humans; Kidney Diseases; Male; Nephrosis; Nephrotic Syndrome; Proteinuria; Purpura; Warfarin

Topics: Animals; Cortisone; Fatty Acids, Nonesterified; Kidney; Kidney Diseases; Kidney Glomerulus; Liver; Male; Mononuclear Phagocyte System; Organ Size; Rabbits; Staining and Labeling; Warfarin

Topics: Adolescent; Adult; Angiocardiography; Cardiac Catheterization; Electrocardiography; Extracorporeal Circulation; Female; Follow-Up Studies; Heart Valve Prosthesis; Hemorrhage; Humans; Hypothermia, Induced; Infections; Jaundice; Kidney Diseases; Male; Methods; Middle Aged; Mitral Valve Insufficiency; Myocardial Infarction; Postoperative Care; Postoperative Complications; Pulmonary Emphysema; Rheumatic Heart Disease; Suture Techniques; Thromboembolism; Warfarin

Topics: Diagnosis, Differential; Female; Hematoma; Hematuria; Hemorrhage; Humans; Kidney Diseases; Kidney Neoplasms; Male; Middle Aged; Urography; Warfarin

Topics: Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Cholesterol; Coronary Disease; Diet; Dietary Fats; Factor IX; Factor X; Ischemia; Kidney Diseases; Lipidoses; Pathology; Pharmacology; Phospholipids; Rats; Research; Warfarin

Topics: Anticoagulants; Arrhythmias, Cardiac; Blood Cell Count; Cerebrovascular Disorders; Coronary Disease; Diabetes Mellitus; Dicumarol; Heart Failure; Heparin; Humans; Hypertension; Kidney Diseases; Liver Diseases; Myocardial Infarction; Peptic Ulcer; Pulmonary Embolism; Shock; Thromboembolism; Thrombophlebitis; Thrombosis; Varicose Veins; Warfarin