warfarin and Acute-Kidney-Injury

Anticoagulant-related nephropathy (ARN) is a novel and not well-studied cause of acute kidney injury (AKI). The prevalence of ARN varies significantly between studies and is estimated at 20% in patients treated with warfarin. Patients with ARN have a significantly higher mortality risk and an increased risk of chronic kidney disease (CKD). Unexplained AKI with hematuria are clinical manifestations of ARN. In most cases, ARN is diagnosed within the first 2 months of anticoagulant therapy, but later ARN occurrence is possible. Among the studied anticoagulants, most data concern warfarin toxicity, whereas cases of ARN caused by direct oral anticoagulants (DOACs) have also been presented. Tubular obstruction by red blood cell casts or hemoglobin and iron tubular toxicity are the postulated mechanisms of ARN. On the molecular level, the inhibition of thrombin and protease-activated receptor-1 (PAR-1), leading to endothelial susceptibility to damage or abnormal protein C endothelial signaling, is suggested to contribute to ARN. Older age, impaired kidney function, hypertension, and diabetes mellitus are the main risk factors for ARN, but their significance may differ between anticoagulants. From therapeutic options, the withdrawal of the anticoagulant and the administration of its antidote, as well as corticosteroids or N-acetylcysteine, are proposed. Since the number of patients with kidney diseases on anticoagulants increases, and DOACs are starting to be more useful in this group of patients, we aim to summarize the pathogenesis, clinical picture and possible ways of treatment of DOAC-induced ARN.

Topics: Acute Kidney Injury; Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Renal Insufficiency, Chronic; Rivaroxaban; Warfarin

Acute kidney injury in the context of nephrotic syndrome is a serious and alarming clinical problem. Largely, acute kidney injury is a relatively frequent complication among patients with comorbidities while it has been independently associated with an increased risk of adverse outcomes, including death and chronic kidney disease. Nephrotic syndrome, without hematuria or with minimal hematuria, includes a list of certain glomerulopathies; minimal change disease, focal segmental glomerulosclerosis and membranous nephropathy. In the light of primary nephrotic syndrome, pathophysiology of acute kidney injury is differentiated by the nature of the primary disease and the severity of the nephrotic state. This review aims to explore the clinical circumstances and pathogenetic mechanisms of acute kidney injury in patients with nephrotic syndrome due to primary glomerulopathies, focusing on newer perceptions regarding the pathogenesis and management of this complicated condition, for the prompt recognition and timely initiation of appropriate treatment in order to restore renal function to its baseline level. Prompt recognition of the precise cause of acute kidney injury is crucial for renal recovery. Clinical characteristics, laboratory and serological findings along with histopathological findings, if required, will reveal the implicated pathway leading to individualized approach and management.

Topics: Acute Kidney Injury; Anticoagulants; Biopsy; Calcineurin Inhibitors; Glomerulosclerosis, Focal Segmental; Humans; Kidney; Nephritis, Interstitial; Nephrotic Syndrome; Renal Veins; Thrombosis; Warfarin

Anticoagulant-related nephropathy (ARN) is a newly recognized form of AKI in which overanticoagulation causes profuse glomerular hemorrhage, which manifests on renal biopsy as numerous renal tubules filled with red cells and red cell casts. The glomeruli show changes, but they are not sufficient to account for the glomerular hemorrhage. We were the first to study ARN, and since then, our work has been confirmed by numerous other investigators. Oral anticoagulants have been in widespread use since the 1950s; today, >2 million patients with atrial fibrillation take an oral anticoagulant. Despite this history of widespread and prolonged exposure to oral anticoagulants, ARN was discovered only recently, suggesting that the condition may be a rare occurrence. This review chronicles the discovery of ARN, its confirmation by others, and our animal model of ARN. We also provide new data on analysis of "renal events" described in the

Topics: Acute Kidney Injury; Administration, Oral; Animals; Anticoagulants; Creatinine; Disease Models, Animal; Humans; International Normalized Ratio; Kidney; Practice Guidelines as Topic; Renal Insufficiency, Chronic; Risk Factors; Warfarin

Warfarin related nephropathy is one of the potential complications of warfarin therapy. Despite the well described histological entity, the clinical course and approach to warfarin related nephropathy in patients requiring life-long anticoagulation is however not well described in the literature.. We report the clinical course of a 56 years old Chinese lady who presented with over anti-coagulation and acute kidney injury while on warfarin therapy for permanent atrial fibrillation and mechanical valve replacement. Renal biopsy was performed as the acute kidney injury was persistent despite normalization of the International Normalized Ratio and the diagnosis of warfarin related nephropathy was made. Temporary interruption of anti-coagulation, in combination with oral N-acetylcysteine resulted in subsequent stabilization of renal function.. The diagnosis of warfarin induced nephropathy should be considered in patients presenting with unexplained acute kidney injury and over anti-coagulation. Awareness of this clinical entity is important for clinician managing anti-coagulation therapy and renal function should be monitored regularly in patients who are on warfarin therapy.

Topics: Acetylcysteine; Acute Kidney Injury; Anticoagulants; Atrial Fibrillation; Female; Free Radical Scavengers; Heart Valve Prosthesis; Humans; Middle Aged; Warfarin; Withholding Treatment

Anticoagulant-related nephropathy, a recently recognized entity, manifests as unexplained acute kidney injury in the setting of excessive anticoagulation with oral agents. Histologic findings in warfarin-related nephropathy include glomerular hemorrhage and renal tubular obstruction by red blood cells. Affected patients are at increased risk of mortality as well as irreversible kidney injury. Patients with chronic kidney disease are particularly vulnerable to this complication. Similar case reports of anticoagulant-related nephropathy have been linked to the more novel oral anticoagulant, dabigatran. Anticoagulant-related nephropathy has been successfully reproduced in rat models. These animal models shed light on the pathogenesis of the disease including the potential role of direct thrombin and protease-activated receptor-1 inhibition. Warfarin and dabigatran also cause an increase in systolic blood pressure in rats, a risk factor for developing nephropathy. This article reviews the current evidence for anticoagulant-related nephropathy and provides data for the suggested possible mechanisms underlying this adverse effect.

Topics: Acute Kidney Injury; Administration, Oral; Animals; Anticoagulants; Dabigatran; Disease Models, Animal; Humans; Rats; Renal Insufficiency, Chronic; Risk Factors; Warfarin

Warfarin is widely prescribed for patients with atrial fibrillation. In addition to unexpected bleeding, allergic skin reaction is one of its uncommon adverse effects. We herein report an 89-year-old man who, after taking warfarin for 4 years, suffered extensive skin eruptions. The skin biopsy disclosed leukocytoclastic vasculitis. The causal relationship between skin lesions and warfarin was confirmed after re-challenge of warfarin. A literature review revealed only 13 such cases reported from 1980 to 2011. Clinicians should be aware of this potential adverse effect of warfarin.

Topics: Acute Kidney Injury; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Coronary Disease; Drug Eruptions; Heart Failure; Humans; Hypertension; Male; Proteinuria; Taiwan; Thrombophilia; Vasculitis, Leukocytoclastic, Cutaneous; Warfarin

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

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

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Azetidines; Cardiomyopathies; Ezetimibe; Female; Heart Failure; Humans; Kidney Failure, Chronic; Male; Middle Aged; Pyrazoles; Pyridones; Recurrence; Risk; Seizures; Simvastatin; Ultrasonography; Warfarin

Apixaban is eliminated by the kidneys and in acute kidney injury (AKI) there is potential for an increase in apixaban exposure and bleeding events. In one instance, data have shown higher than normal bleed risk in patients with AKI, unless calibrated anti-factor Xa monitoring is used, which is not widely available.. To evaluate bleeding with apixaban administration to hospitalized patients with an AKI in an unmonitored real-world scenario.. We conducted a retrospective study of patients admitted to a large urban academic teaching hospital from April 2015 to March 2022, who received apixaban for venous thromboembolism or nonvalvular atrial fibrillation (NVAF). The primary outcome evaluated major bleeding when apixaban was administered to patients with or without an AKI.. A total of 232 patients were evaluated (116 per group). Most patients (79.7%) were on apixaban for NVAF, 32.7% had chronic kidney disease, 58.2% were on a medication increasing bleed risk, and HAS-BLED score was a median of 2 in both groups. No differences were noted between groups for bleeding (AKI group 7.8% vs non-AKI 3.4%;. Although no differences between groups were noted, apixaban use in the AKI group resulted in a higher than normally reported incidence of apixaban-associated major bleeding, and concomitant antiplatelet use increased bleed risk as well. Cautious use of apixaban and further investigation with larger studies are warranted in this area.

Topics: Acute Kidney Injury; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Pyridones; Retrospective Studies; Stroke; Warfarin

Direct oral anticoagulants (DOACs) are preferred over warfarin for many indications, though their safety has not been well established in patients with acute renal impairment.. The purpose of this study was to evaluate the frequency of bleeding complications associated with DOACs compared with warfarin in patients admitted to the hospital with acute kidney injury (AKI).. This was a retrospective cohort study evaluating patients admitted to the Penn Medicine Lancaster General Hospital with a diagnosis of AKI from October 2017 through September 2021 and receiving therapy with oral anticoagulants. Comparing DOACs with warfarin, the primary endpoint was the percent frequency of composite major and minor bleeding during the admission and within 30 days of discharge.. There were 112 hospitalization encounters included in the study. Of these, 42 (37.5%) patients were receiving warfarin and 70 (62.5%) patients were receiving DOAC therapy before admission. There was a higher frequency of the primary endpoint of bleeding in patients receiving DOACs as compared with warfarin, though this was not statistically significant (18.5% vs. 11.9%, respectively,. Direct oral anticoagulants and warfarin were associated with statistically similar rates of bleeding in patients presenting with AKI. Further research is necessary to elucidate if DOACs are safer than warfarin in this patient population.

Topics: Acute Kidney Injury; Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Retrospective Studies; Warfarin

Anticoagulation with either a vitamin K antagonist or a direct oral anticoagulant may be associated with AKI. Our objective was to assess the risk of AKI among elderly individuals with atrial fibrillation newly prescribed a direct oral anticoagulant (dabigatran, rivaroxaban, or apixaban) versus warfarin.. Our population-based cohort study included 20,683 outpatients in Ontario, Canada, ≥66 years with atrial fibrillation who were prescribed warfarin, dabigatran, rivaroxaban, or apixaban between 2009 and 2017. Inverse probability of treatment weighting on the basis of derived propensity scores for the treatment with each direct oral anticoagulant was used to balance baseline characteristics among patients receiving each of the three direct oral anticoagulants compared with warfarin. Cox proportional hazards regression was performed in the weighted population to compare the association between the prescribed anticoagulant and the outcomes of interest. The exposure was an outpatient prescription of warfarin or one of the direct oral anticoagulants. The primary outcome was a hospital encounter with AKI, defined using Kidney Disease Improving Global Outcomes thresholds. Prespecified subgroup analyses were conducted by eGFR category and by the percentage of international normalized ratio measurements in range, a validated marker of anticoagulation control.. Each direct oral anticoagulant was associated with a significantly lower risk of AKI compared with warfarin (weighted hazard ratio, 0.65; 95% confidence interval, 0.53 to 0.80 for dabigatran; weighted hazard ratio, 0.85; 95% confidence interval, 0.73 to 0.98 for rivaroxaban; and weighted hazard ratio, 0.81; 95% confidence interval, 0.72 to 0.93 for apixaban). In the subgroup analysis, the lower risk of AKI associated with each direct oral anticoagulant was consistent across each eGFR strata. The risk of AKI was significantly lower among users of each of the direct oral anticoagulants compared with warfarin users who had a percentage of international normalized ratio measurements ≤56%.. Direct oral anticoagulants were associated with a lower risk of AKI compared with warfarin.

Topics: Acute Kidney Injury; Age Factors; Aged; Aged, 80 and over; Antithrombins; Atrial Fibrillation; Comorbidity; Dabigatran; Databases, Factual; Factor Xa Inhibitors; Female; Glomerular Filtration Rate; Humans; Male; Ontario; Pyrazoles; Pyridones; Risk Assessment; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome; Warfarin

Rhabdomyolysis is a relatively common and life-threatening disease that is sometimes complicated by acute kidney injury (AKI). Several causes have been reported, divided into traumatic and non-traumatic causes. We herein report a patient with rhabdomyolysis with AKI caused by bilateral iliopsoas hematoma. This patient had atrial fibrillation that was poorly controlled with warfarin, and bilateral iliopsoas hematoma was caused by turnover without a history of high-energy injury. Treatment with the rapid neutralization of warfarin improved his clinical condition without complications. We should pay close attention to episodes of turnover among elderly patients receiving anticoagulant therapy.

Topics: Acute Kidney Injury; Aged; Anticoagulants; Atrial Fibrillation; Hematoma; Humans; Male; Muscle, Skeletal; Retroperitoneal Space; Rhabdomyolysis; Tomography, X-Ray Computed; Warfarin

Topics: Acute Kidney Injury; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Comorbidity; Female; Humans; Kidney Function Tests; Male; Renal Insufficiency, Chronic; Risk Adjustment; Risk Factors; Rivaroxaban; Stroke; Treatment Outcome; United States; Warfarin

Anticoagulant-related nephropathy is an acute kidney injury (AKI) associated with excessive anticoagulation. The nature of the association between excessive anticoagulation with warfarin and AKI and its incidence remain unclear. To evaluate the incidence of AKI in excessively anticoagulated patients taking warfarin and examine potential risk factors. A retrospective chart review was performed in patients on chronic warfarin. The primary outcome was AKI, defined as an acute increase in creatinine of > 26.5 µmol/L within 7-14 days of an international normalized ratio (INR) ≥ 4.0. 292 patients with an INR ≥ 4.0 were included. 101 patients had CKD and 191 did not have CKD. Of the 292 patients with an INR ≥ 4.0, 38 (13%) had an AKI. In univariable analyses, CKD [odds ratio (OR) 2.1, 95% confidence interval (CI) 0.99-4.43] and use of renin-angiotensin system (RAS) blockers and/or diuretics (OR 3.85; 95% CI 1.15-20.15) were significantly associated with the risk of AKI. In a binomial logistic regression model, use of RAS blockers and/or diuretics was the only significant predictor of AKI (OR 3.4; 95% CI 1.02-11.76). Use of RAS blockers and/or diuretics significantly increased the risk of AKI in patients with warfarin-related excessive anticoagulation. Further prospective studies examining the association of high INRs and AKI are needed.

Topics: Acute Kidney Injury; Aged; Creatinine; Diuretics; Humans; Incidence; International Normalized Ratio; Middle Aged; Renin-Angiotensin System; Retrospective Studies; Risk Factors; Warfarin

A 55-year-old man with Marfan syndrome taking warfarin for anticoagulant therapy after aortic valve replacement developed acute kidney injury (serum creatinine level of 9.01 mg/dL) and gross macrohematuria. Renal biopsy showed red cell casts in the renal tubules, glomerular crescent formation in the glomeruli with immunoglobulin A deposition, and global sclerosis. Based on these findings, the patient was diagnosed with warfarin-related nephropathy with acute kidney injury characterized by immunoglobulin A nephropathy with crescents. The warfarin was withdrawn, and his hematuria and renal function improved without immunosuppressive agents.

Topics: Acute Kidney Injury; Anticoagulants; Aortic Valve Insufficiency; Glomerulonephritis, IGA; Hematuria; Humans; Kidney; Kidney Glomerulus; Kidney Tubules; Male; Marfan Syndrome; Middle Aged; Treatment Outcome; Warfarin

Whether or not non-vitamin K antagonist oral anticoagulants (NOACs) are associated with a lower risk of acute kidney injury (AKI) in patients with non-valvular atrial fibrillation (NVAF) remains unknown in real world practice.. In this nationwide retrospective cohort study, 1507, 3200, 5765 and 4227 NVAF patients with chronic kidney disease (CKD) and 4368, 16,945, 22,301, and 16,908 NVAF patients without CKD taking apixaban, dabigatran, rivaroxaban, and warfarin, respectively, from June 1, 2012 to December 31, 2016 were enrolled from the Taiwan National Health Insurance Program. Propensity-score weighted method was used to balance covariates across study groups. Patients were followed until occurrence of AKI or end date of study.. Three NOACs were all associated with a significantly lower risk of AKI compared with warfarin for both CKD-free (hazard ratio, [95% confidential interval]; 0.65, [0.60-0.72] for apixaban; 0.68, [0.64-0.74] for dabigatran; 0.73, [0.68-0.79] for rivaroxaban) and CKD cohorts (0.50, [0.45-0.56] for apixaban; 0.54, [0.49-0.59] for dabigatran; 0.53, [0.49-0.58] for rivaroxaban). The annual incidence of AKI for all NOACs and warfarin increased gradually as the increment of CHA. All three NOACs are associated with a lower risk of AKI than warfarin among Asians with NVAF in real-world practice.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anticoagulants; Antithrombins; Asian People; Atrial Fibrillation; Cohort Studies; Dabigatran; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Taiwan; Treatment Outcome; Warfarin

Dengue fever is a mosquito-borne viral disease with a very high incidence in Southeast Asia. Most patients with dengue fever recover following a self-limiting febrile illness, while a small proportion may progress to develop severe disease with complications such as acute liver failure, acute kidney injury, and multiorgan failure. Secondary bacterial infections and thrombotic events are very rare.. A 38-year-old previously healthy Sri Lankan woman from Colombo, Sri Lanka, presented with dengue shock syndrome leading to acute liver failure and kidney injury. She was managed with intravenously administered fluid resuscitation with close monitoring of her hemodynamic status, and hemodialysis. Her renal and liver functions and platelet count improved gradually, but the fever persisted and there was a neutrophil leukocytosis. A clinical examination and investigations to identify a focus of secondary infection revealed staphylococcal infective endocarditis. She was started on intravenously administered vancomycin, but as the response was poor the antibiotic was changed to intravenously administered linezolid, to which the response was good. She also developed right proximal femoral deep vein thrombosis, and was commenced on subcutaneous enoxaparin and warfarin. Enoxaparin was stopped after her international normalized ratio reached the desirable range, and warfarin was continued for 3 months.. Dengue virus is known to cause endothelial dysfunction that allows bacteria to invade tissues, defective functioning and reduction in the number of cells of the immune system, and alteration of cytokines leading to immune dysregulation, predisposing patients to develop secondary bacterial infections. Evidently, patients with dengue fever who have prolonged fever (more than 5 days) and acute kidney injury are at high risk for concurrent bacteremia. Dengue virus interferes with the components of the anti-clotting pathway, such as thrombomodulin-thrombin-protein C complex. It also activates endothelial cells and increases the expression of procoagulant factors. These factors may predispose patients with dengue viral infections to develop thrombotic complications. Therefore it is important to be aware of the possibility of serious secondary bacterial infections occurring following dengue viral infections, especially in patients with prolonged fever and acute kidney injury, and to keep in mind that thrombotic events may occur as complications of dengue viral infections.

Topics: Acute Kidney Injury; Adult; Anticoagulants; Coinfection; Dengue; Endocarditis, Bacterial; Enoxaparin; Female; Fluid Therapy; Humans; Linezolid; Liver Failure, Acute; Renal Dialysis; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Acute Kidney Injury; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Warfarin

Topics: Acute Kidney Injury; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; 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

Warfarin-related nephropathy (WRN) is a newly recognized entity, which is characterized by the occlusion of renal tubules by red blood cells following glomerular hemorrhage in a patient overexposed to warfarin (international normalized ratio>3).. We report a 70-year-old man with no previous renal condition who developed WRN when his INR was>12. He did not fully recover his previous renal function.. The diagnosis of WRN should be considered whenever INR exceeds 3 in patients exposed to warfarin, particularly in the presence of hematuria. Vitamin K is the only therapeutic option.

Topics: Acute Kidney Injury; Aged; Anticoagulants; Hematuria; Humans; Male; Medication Errors; Renal Dialysis; Warfarin

Warfarin is the most prescribed oral anticoagulant. Adverse renal effect from warfarin therapy are uncommon and Thailand is not acquainted. Warfarin-related nephropathy (WRN) is a newly recognized complication of warfarin treatment, especially in patients with chronic kidney disease. The authors hereby report a 56-year-old man who developed gross hematuria and severe acute kidney injury (AKI) necessitating hemodialysis, following supra-therapeutic INR level. Renal pathology revealed extensive intratubular obstruction with red blood cell casts. From the literature, there were only twelve case reports of WRN, which were confirmed by renal histopatology. Renal survival of this condition was unsatisfactory. However, our patient was dialysis-independent after vitamin K treatment and temporary warfarin discontinuation. To the best of our knowledge, this is the first case report of biopsy-proven WRN in Thailand.

Topics: Acute Kidney Injury; Anticoagulants; Humans; Male; Middle Aged; Renal Dialysis; Thailand; Warfarin

Excessive anticoagulation with warfarin can result in acute kidney injury (AKI) by causing glomerular hemorrhage and renal tubular obstruction by red blood cell (RBC) casts in some patients, especially in those with chronic kidney disease (CKD). This condition was described as warfarin-related nephropathy (WRN). Recent evidence suggests that WRN-like syndromes are not confined to anticoagulation with warfarin, but may be seen with other anticoagulants, such as dabigatran. The aim of this study was to investigate dabigatran effects on kidney function in an animal model of CKD and possible pathogenic mechanisms of AKI.. Control and 5/6 nephrectomy rats were treated with different doses of dabigatran and protease-activated receptor 1 (PAR-1) inhibitor SCH79797.. Dabigatran resulted in changes in coagulation in rats similar to those in humans at 50 mg/kg/day. Dabigatran resulted in a dose-dependent increase in serum creatinine (Scr) and hematuria in both control and 5/6 nephrectomy rats. SCH79797 also increased Scr and hematuria, more prominent in animals with CKD. Morphologically, numerous RBC tubular casts were seen in 5/6 nephrectomy rats treated with either dabigatran or SCH79797 and only occasional RBC casts in control rats.. Our data indicate that WRN represents part of a broader syndrome, anticoagulant-related nephropathy (ARN). ARN, at least partially, is mediated via PAR-1. Our findings suggest that not only CKD patients, but other patients as well, are at high risk of developing AKI if the therapeutic range of anticoagulation with dabigatran is exceeded. Close monitoring of kidney function in patients on dabigatran therapy is warranted.

Topics: Acute Kidney Injury; Animals; Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Disease Models, Animal; Hemorrhage; Kidney; Kidney Glomerulus; Male; Rats; Rats, Sprague-Dawley; Warfarin

Topics: Acute Kidney Injury; Anticoagulants; Female; Hematuria; Humans; Male; Warfarin

Topics: Acute Kidney Injury; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Embolism, Cholesterol; Enoxaparin; Fatal Outcome; Female; Fibrinolytic Agents; Humans; Infarction, Middle Cerebral Artery; Recombinant Proteins; Syndrome; Thrombolytic Therapy; Tissue Plasminogen Activator; Toes; Warfarin

Dabigatran is a reversible direct thrombin inhibitor recently approved for stroke prevention in patients with atrial fibrillation. An increasing number of patients receiving dabigatran present to the emergency department (ED) with bleeding complications. Unlike vitamin K antagonists, there are no accepted reversal agents for dabigatran and the data on course and management of bleeding complications are limited. The study objective is to describe the course of bleeding complications in patients admitted through the ED who are prescribed dabigatran in comparison with warfarin therapy.. This was a prospective observational study of ED patients under treatment with dabigatran or warfarin who were admitted with bleeding complications during a 6-month period. Patient demographics, laboratory results, bleeding site, interventions, and outcomes are reported.. There were 15 and 123 patients admitted with dabigatran and warfarin-induced bleeding complications, respectively. Of the warfarin patients, 25 charts were randomly chosen for extraction. Patients with dabigatran-induced bleeding had a shorter length of stay (3.5 versus 6.0 days) and were older (77 versus 70 years). Patients receiving dabigatran were more likely to have gastrointestinal bleeding (80% versus 48%) and less likely to have intracranial bleeding (0% versus 32%) than those receiving warfarin. Of patients with dabigatran-induced bleeding, 53% presented with an acute kidney injury.. Our patients with dabigatran-induced bleeding had a more benign clinical course with a shorter length of stay compared with patients with warfarin-induced bleeding. As was the case in previous published reports, there were fewer intracranial hemorrhages in patients receiving dabigatran than warfarin. Sustaining an acute kidney injury potentially predisposes patients to bleeding while receiving dabigatran.

Topics: Acute Kidney Injury; Age Factors; Aged; Aged, 80 and over; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Emergency Service, Hospital; Female; Hemorrhage; Humans; Length of Stay; Male; Middle Aged; Prospective Studies; Stroke; Warfarin

Warfarin-related nephropathy (WRN) is a recently described disease entity, in which excessive warfarinization (international normalized ratio (INR) >3.0) causes acute kidney injury. Previous reports regarding WRN included few Asian patients who might have differed from the western WRN patients in terms of genetic and environmental factors.. During the period of March 2003 to December 2011, the data about a total of 1297 patients who had serum creatinine (sCr) level measured within 1 week after INR >3.0 and within 6 months before INR >3.0 was analyzed through the retrospective review of electronic medical records of a single tertiary hospital in Korea.. WRN developed in 19.3% of patients having excessive warfarinization. The incidence was higher in the chronic kidney disease (CKD) group than the non-CKD group. The risk of WRN increased as the basal serum albumin level decreased and was strongly associated with highest quartile serum AST level at post INR elevation and the presence of congestive heart failure. But the presence of atrial fibrillation was protective against the development of WRN. Neither the presence of CKD nor basal estimated glomerular filtration rate (eGFR) was an independent risk factor for WRN. Despite no difference in the basal sCr level, the sCr level was higher in patients with WRN than those without WRN after follow-up. The mortality rates were also higher in patients with WRN.. WRN developed in 19.3% of patients having excessive warfarinization. A lower basal serum albumin, highest quartile serum AST level at post INR elevation, and congestive heart failure were associated with the occurrence of WRN. The development of WRN adversely affected renal and patient outcomes.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anticoagulants; Asian People; Creatinine; Female; Heart Failure; Humans; Kidney Failure, Chronic; Male; Middle Aged; Retrospective Studies; Risk Factors; Serum Albumin; Survival Analysis; Warfarin

Warfarin-related nephropathy (WRN) occurs under conditions of overanticoagulation with warfarin. WRN is characterized by glomerular hemorrhage with occlusive tubular red blood cell (RBC) casts and acute kidney injury (AKI). Herein we test the hypothesis that oxidative stress plays a role in the AKI of WRN. 5/6 Nephrectomy rats were treated with either warfarin (0.04 mg·kg⁻¹·day⁻¹) alone or with four different doses of the antioxidant N-acetylcysteine (NAC). Also tested was the ability of our NAC regimen to mitigate AKI in a standard ischemia-reperfusion model in the rat. Warfarin resulted in a threefold or greater increase in prothrombin time in each experimental group. Serum creatinine (Scr) increased progressively in animals receiving only warfarin + vehicle. However, in animals receiving warfarin + NAC, the increase in Scr was lessened, starting at 40 mg·kg⁻¹·day⁻¹ NAC, and completely prevented at 80 mg·kg⁻¹·day⁻¹ NAC. NAC did not decrease hematuria or obstructive RBC casts, but mitigated acute tubular injury. Oxidative stress in the kidney was increased in animals with WRN and it was decreased by NAC. The NAC regimen used in the WRN model preserved kidney function in the ischemia-reperfusion model. Treatment with deferoxamine (iron chelator) did not affect WRN. No iron was detected in tubular epithelial cells. In conclusion, this work taken together with our previous works in WRN shows that glomerular hematuria is a necessary but not sufficient explanation for the AKI in WRN. The dominant mechanism of the AKI of WRN is tubular obstruction by RBC casts with increased oxidative stress in the kidney.

Topics: Acetylcysteine; Acute Kidney Injury; Animals; Creatinine; Deferoxamine; Erythrocytes; Male; Nephrectomy; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Urine; Warfarin

Cholesterol crystal embolism (CCE) is a serious complication associated with invasive vascular procedures. The prognosis of the renal involvement type of CCE is very poor, and there is currently no established treatment, other than supportive therapy. We herein report four cases of CCE with severe atherosclerosis wherein the renal function progressively deteriorated after cardiac catheterization. In three of the four patients, low-dose corticosteroids (0.3 mg/kg/day) improved the renal function, whereas the fourth patient died from CCE of the digestive system. This report reviews the literature on CCE and discusses possible therapeutic options.

Topics: Acute Kidney Injury; Aged; Aortography; Cardiac Catheterization; Comorbidity; Coronary Angiography; Coronary Disease; Crystallization; Embolism, Cholesterol; Fatal Outcome; Humans; Intestinal Perforation; Intestines; Ischemia; Leg; Livedo Reticularis; Male; Middle Aged; Peripheral Vascular Diseases; Prednisolone; Recurrence; Toes; Warfarin

Warfarin is a well-established cause of gross hematuria. However, impaired kidney function does not occur except in the rare instance of severe blood loss or clot formation that obstructs the urinary tract. It has been recently described an entity called warfarin-related nephropathy, in which acute kidney injury is caused by glomerular hemorrhage and renal tubular obstruction by red blood cell casts. We report a patient under warfarin treatment with chronic kidney disease, macroscopic hematuria and acute kidney injury. A renal biopsy showed massive occlusion of renal tubules by red blood cells and casts. The possible relationship of the warfarin therapy, intratubular hemorrhage and acute kidney injury is discussed.

Topics: Acute Kidney Injury; Aged; Anticoagulants; Hematuria; Humans; Kidney Glomerulus; Male; Renal Insufficiency, Chronic; Warfarin

The patient was an 82-year-old female. She had been treated with warfarin for atrial fibrillation that developed after a heart valve replacement operation. She was admitted because of a progressive loss of renal function together with persistent microscopic hematuria and proteinuria. Although the renal biopsy showed only focal mononuclear cell infiltration and mild mesangial expansion in the glomeruli, the occlusive red blood cell casts were remarkable in the tubules and were accompanied by inflammatory and edematous changes in the surrounding interstitial area. After the adjustment of an excessively extended prothrombin time, her renal function gradually improved in parallel with the marked decrease in the microhematuria. It was assumed that an acute kidney injury observed in this case was caused by the occlusive red blood cell casts as a result of abnormal hemorrhage in the glomeruli due to focal glomerulonephritis and a warfarin overdose. The present case, therefore, suggests that a warfarin overdose is a potential risk factor for acute kidney injury in the presence of coexisting glomerular injury.

Topics: Acute Kidney Injury; Aged, 80 and over; Female; Glomerulonephritis, IGA; Hematuria; Humans; Kidney Glomerulus; Warfarin

Topics: Acute Kidney Injury; Animals; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Rats; Warfarin

Warfarin-related nephropathy is reported to occur with an INR >3.0 as a result of glomerular bleeding. There is a lack of prospective studies examining the effect of supratherapeutic warfarin anticoagulation on haematuria and acute kidney injury (AKI). Older patients may be susceptible due to greater warfarin use, prevalence of kidney disease and comorbidities. The objective of this study was to determine the incidence and nature of haematuria and AKI in older patients on warfarin and to determine any association with high INR levels.. This was a prospective, observational study of 150 elderly patients receiving warfarin anticoagulation who were acutely hospitalised in a tertiary hospital. AKI was assessed using RIFLE criteria. Urinalysis was performed to quantify haematuria, characterise erythrocyte morphology and measure the albumin-creatinine ratio. Positive cases received follow-up at 4-6 weeks to determine resolution.. An INR >3.0 was found in 54 % of patients. Pre-admission antibiotic use increased the risk of excessive anticoagulation. The incidence of isolated AKI, isolated haematuria and both was 18.7, 13.3 and 12 %, respectively. Factors associated with a higher risk of haematuria were an INR >4.0, non-urinary infection, catheterisation and albuminuria. Most cases of AKI were mild, and there was no demonstrable correlation between the admission INR and AKI. Admission with heart failure was significantly associated with an increased risk of persistent kidney impairment at follow-up.. Supratherapeutic warfarin anticoagulation was associated with an increased risk of haematuria, but not with AKI. The majority of cases of haematuria were transient.

Topics: Acute Kidney Injury; Aged, 80 and over; Anticoagulants; Female; Hematuria; Hospitalization; Humans; Male; Prospective Studies; Warfarin

Topics: Acute Kidney Injury; Adult; Child; Cohort Studies; Cyclophosphamide; Dipyridamole; Drug Therapy, Combination; Female; Follow-Up Studies; Glomerulonephritis, IGA; Humans; Male; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Treatment Outcome; Warfarin

Congenital anomalies of the inferior vena cava (IVC) are rare, but recognized, causing deep venous thrombosis. We present a case of a 50-year-old patient with trauma who suffered an intracranial hemorrhage secondary to a fall while on anticoagulation for deep vein thromboses. Venous return from the lower extremities was determined to be through dilated lumbar venous collaterals into the azygous and hemiazygous systems. A second interesting anatomic finding was a hypoplastic left kidney.

Topics: Accidental Falls; Acute Kidney Injury; Anticoagulants; Azygos Vein; Collateral Circulation; Dilatation, Pathologic; Humans; Intracranial Hemorrhage, Traumatic; Kidney; Magnetic Resonance Angiography; Male; Middle Aged; Phlebography; Regional Blood Flow; Vascular Malformations; Vena Cava, Inferior; Venous Thrombosis; Warfarin

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

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

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Anticoagulants; Blood Coagulation Disorders; Cardiomyopathy, Dilated; Drug Interactions; Hematuria; Humans; International Normalized Ratio; Levofloxacin; Male; Ofloxacin; Shock; Urinary Tract Infections; Warfarin

Acute renal failure due to bilateral hematoma is a rare complication of anticoagulant warfarin therapy. A 43-year-old man presented with complaints of hematuria and abdominal pain. He had been receiving warfarin for six years, after placement of an aortic valve prosthesis. One week prior to admission, he sustained a urinary tract infection which was treated with third-generation cephalosporin and indomethacin. His serum creatinine level was 1.8 mg/dl with an INR of 15. Three days later, he developed anuria and was treated with hemodialysis. Renal ultrasonography disclosed moderate bilateral hydronephrosis. Computed tomography without contrast enhancement showed bilateral extensive hyperdense thickening of the renal and ureteral walls and high-attenuation areas. Conservative treatment was preferred and diuresis resumed spontaneously, lumbar pain disappeared, and serum creatinine level returned to normal. One month later, renal computed tomography was found normal.

Topics: Abdominal Pain; Acute Kidney Injury; Adult; Anticoagulants; Diagnosis, Differential; Emergency Treatment; Hematoma; Hematuria; Humans; Male; Radiography; Renal Dialysis; Warfarin

Topics: Acute Kidney Injury; Anti-Inflammatory Agents; Anticoagulants; Biopsy; Cyclophosphamide; Diagnosis, Differential; Female; Heparin, Low-Molecular-Weight; Humans; Immunoglobulin A; Immunosuppressive Agents; Kidney Tubules; Methylprednisolone; Middle Aged; Necrosis; Nephrotic Syndrome; Prednisone; Radiography; Renal Veins; Venous Thrombosis; Warfarin

The use of warfarin is complicated by its narrow therapeutic index. The risk of severe complications in the form of haemorrhage is significantly increased by an elevated degree of anticoagulation. We present a case in which a patient in stable warfarin treatment was admitted with acute renal failure and extremely high international normalized ratio (INR). No single mechanism can fully explain this. We find that it was probably caused by accumulation of active metabolites, an inhibitory factor in uraemic blood, which reduces hepatic metabolism and a genotype with an unstable metabolism of warfarin.

Topics: Acute Kidney Injury; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Genotype; Humans; International Normalized Ratio; Male; Middle Aged; Risk Factors; Warfarin

Acute kidney injury (AKI) during warfarin therapy usually is hemodynamic secondary to massive blood loss. Here, we report pathological findings in kidney biopsy specimens from 9 patients with warfarin overdose, hematuria, and AKI. Kidney biopsy specimens from patients on warfarin therapy with AKI were identified in our database within a 5-year period. Each kidney biopsy specimen was evaluated by using semiquantitative morphometric techniques, and medical history was reviewed for conditions explaining AKI. Biopsy specimens with morphological findings of active glomerulonephritis and active inflammatory lesions were excluded from the study. Biopsy specimens from 9 patients were selected. At presentation with AKI, each patient had an abnormal international normalized ratio (mean 4.4 +/- 0.7 IU) and increased serum creatinine level (mean, 4.3 +/- 0.8 mg/dL). Morphologically, each biopsy specimen showed evidence of acute tubular injury and glomerular hemorrhage: red blood cells (RBCs) in Bowman space and numerous occlusive RBC casts in tubules. Each biopsy specimen showed chronic kidney injury. Six of 9 patients did not recover from AKI. These data suggest that warfarin therapy can result in AKI by causing glomerular hemorrhage and renal tubular obstruction by RBC casts. Our experience suggests that this may be a potentially serious complication of warfarin therapy, especially in older patients with underlying chronic kidney injury.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anticoagulants; Biopsy; Erythrocytes; Female; Hematuria; Hemorrhage; Humans; Kidney; Kidney Tubules, Proximal; Male; Middle Aged; Thrombosis; Warfarin

Infective endocarditis is an infection of the endocardium that usually involves the valves and adjacent structures. The classical fever of unknown origin presentation represents a minority of infective endocarditis. The presented case was a 21-yearold young lady presenting with acute renal failure and fever to the emergency room. Cardiac auscultation revealed a soft S1 and 4/6 apical holosystolic murmur extended to axilla. Echocardiography showed mobile fresh vegetation under the mitral posterior leaflet. She was diagnosed as having infective endocarditis. Hemodialysis was started with antimicrobial therapy. However, because of the presence of severe mitral regurgitation with left ventricle dilatation and large mobile vegetation, mitral prosthetic mechanical valve replacement was performed. Although treated with antibiotics combined with surgery, renal functions were deteriorated and progressed to chronic renal failure.

Topics: Acute Disease; Acute Kidney Injury; Adult; Anti-Infective Agents; Anticoagulants; Disease Progression; Endocarditis, Bacterial; Female; Heart Valve Prosthesis; Humans; Kidney Failure, Chronic; Renal Dialysis; Staphylococcal Infections; Staphylococcus aureus; Warfarin

Topics: Acute Kidney Injury; Adult; Anticoagulants; Biopsy; Female; Glomerulosclerosis, Focal Segmental; Hematuria; Humans; Hypertension, Pulmonary; International Normalized Ratio; Lupus Erythematosus, Systemic; Lupus Nephritis; Pneumonia; Pulmonary Embolism; Warfarin

We report a case of an important and uncommon haemorrhagic complication in a patient receiving warfarin treatment. We reflect on the importance of close monitoring of anticoagulant therapy to prevent haemorrhagic complications and to ensure safety in longterm use.

Topics: Acute Kidney Injury; Aged; Anticoagulants; Hematoma; Humans; Male; Medication Errors; Retroperitoneal Space; Warfarin

Female Sprague-Dawley rats underwent right nephrectomy and 40 min left renal artery occlusion (RAO). After 15 min of reflow, polyethylene glycol 1000 (PEG1000) was infused to induce osmotic diuresis and to enable glomerular filtration rate (GFR) measurements. Urine was collected during a 90 min period, and the concentrations of PEG1000, albumin, IgG, IgM and fibrin(ogen)/degradation products (FIB) were assessed both in plasma and urine by radial immuno diffusion technique Groups of rats were subjected to saline + RAO, warfarin + RAO or sham-operation. GFR as measured by PEG1000 clearance averaged 0.61, 0.036 and 0.094 mL/min/100g BW/kidney in sham-operated, saline + RAO and warfarin + RAO rats, respectively. Urinary excretion of albumin and IgG increased substantially in both ischemic groups. IgM was not detected in any of the urine samples. FIB excretion was lowest in the saline + RAO group, possibly due to retention of FIB-containing obstructions in the tubules. Rats subjected to warfarin + RAO had significantly higher excretion of FIB. This result suggests that warfarin does not prevent the glomerular sieving of macromolecules in the glomerular filter, but reduces tubular obstruction by preventing fibrin formation, which may explain its positive effect on GFR.

Topics: Acute Kidney Injury; Animals; Anticoagulants; Female; Fibrin Fibrinogen Degradation Products; Glomerular Filtration Rate; Kidney; Proteinuria; Rats; Rats, Sprague-Dawley; Renal Artery Obstruction; Warfarin

Simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, is widely used to treat hyperlipidaemia. Although myalgias are recognized adverse effects, clinically significant elevations in serum creatine phosphokinase (CPK) levels are uncommon. We describe a case of rhabdomyolysis and acute renal failure associated with concomitant use of simvastatin and warfarin. Rhabdomyolysis and renal failure occurred 7 days after warfarin (5 mg day-1) was added to a chronic stable dose of simvastatin (20 mg day-1) and resolved abruptly after discontinuation of simvastatin. We recommend careful monitoring when warfarin is given to patients receiving simvastatin.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anticoagulants; Creatine Kinase; Drug Interactions; Humans; Hydroxymethylglutaryl CoA Reductases; Male; Rhabdomyolysis; Simvastatin; 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

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Anticoagulants; Cerebrovascular Disorders; Embolism, Cholesterol; Humans; Male; Warfarin

Topics: Acute Kidney Injury; Aged; Female; Hematoma; Hemorrhage; Humans; Metronidazole; Ureteral Diseases; Warfarin

Topics: Acute Kidney Injury; Aged; Diltiazem; Eosinophils; Female; Humans; Kidney Tubules; Myocardial Infarction; Nephritis; Nitroglycerin; Warfarin

During the 13 year period 1971 to 1984 there were 38 pregnancies in 21 renal transplant patients at the Johannesburg Hospital. Twenty-two ended with live births and included two sets of twins; there were nine spontaneous abortions, six therapeutic abortions, and one stillbirth. Maternal complications were mild in the majority but five patients suffered deterioration in renal function, two undergoing transplant nephrectomy as a result of this. There were seven neonatal deaths, including both sets of twins; death was due to prematurity in six and congenital malformation (diaphragmatic hernia) in one. A further infant had congenital pyloric stenosis which was corrected surgically. Pregnancies were analysed according to whether or not their outcome was successful. Those with a successful outcome had less exposure to warfarin during pregnancy (p = 0.0025) and showed a tendency towards lower immunosuppressive doses of prednisone and azathioprine although these did not reach significance. Although these results indicate an unhappy prognosis for both the mother and fetus, two redeeming features are to be noted. Pregnancy outcome improved markedly in the latter years, possibly owing to non-exposure to warfarin, less immunosuppression, and improvement in neonatal care, and four of the five mothers who suffered deterioration in renal function were notoriously unco-operative in their medical care. Pregnancy can only be recommended in the transplanted patient who has stable renal function, is compliant in taking of medications, and whose graft is of such age that the immunosuppressive drug dose is minimal. Warfarin should be avoided.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Abortion, Therapeutic; Acute Kidney Injury; Adolescent; Adult; Dose-Response Relationship, Drug; Female; Fetal Death; Humans; Immunosuppressive Agents; Infant, Newborn; Kidney Transplantation; Patient Compliance; Pregnancy; Pregnancy Complications; Warfarin

1 The decreased binding of drugs and dyes to plasma proteins from male and female rats with acute renal failure has been investigated using equilibrium dialysis at 37 degrees C. 2 Acute renal failure induced by bilateral ligation of the ureters produced a greater than threefold increase in the unbound fraction of o-methyl red relative to normal rat plasma. Unbound dye concentration in plasma from sham-operated control rats was also significantly increased but to a lesser extent. 3 Glycerol-induced acute renal failure produced a significant increase in the unbound fractions of o-methyl red, methyl orange, bromocresol green (BCG), 2-(4'-hydroxybenzeneazo) benzoic acid (HABA), phenytoin and salicylic acid. A marginally significant increase in unbound warfarin concentration was observed. 4 Glycerol-induced renal failure had no effect on total plasma protein concentration and experiments with o-methyl red and salicylic acid indicated that a direct effect of glycerol was not responsible for the diminution of binding. 5 Glycerol-induced acute renal failure, which produced decreases in drug and dye binding similar to those reported for human uraemic plasma, provides a convenient non-surgical animal model for the investigation of this phenomenon.

Topics: Acute Kidney Injury; Animals; Blood Proteins; Coloring Agents; Creatinine; Disease Models, Animal; Female; Glycerol; Male; Phenytoin; Rats; Salicylates; Sex Factors; Urea; Ureter; Warfarin

Serum protein binding of phenylbutazone has been measured in the rat, guinea pig, cat, rabbit and dog, and the influence on it of renal failure induced by uranyl nitrate injection has been studied. In all speciies a clearcut decrease in binding was observed after the occurrence of renal failure; the time course of the fall in binding correlated well with development of renal failure. In further experiments, serum protein binding of two acidic drugs (phenylbutazone, warfarin), two basic drugs (papaverine, quinidine) and one neutral drug (digitoxin) was studied in rabbits with experimental renal failure, and the results compared with those obtained in patients with acute renal failure. In the rabbits, a decrease in the binding of phenylbutazone, warfarin, papaverine and quinidine was found, whereas protein binding of digitoxin was unchanged. In man, there was a definite fall in protein binding of phenylbutazone and digitoxin, a small decrease for warfarin and papaverine, and a slight increase for quinidine.

Topics: Acute Kidney Injury; Animals; Blood Proteins; Cats; Digitoxin; Dogs; Female; Guinea Pigs; Humans; Male; Papaverine; Pharmaceutical Preparations; Phenylbutazone; Protein Binding; Quinidine; Rabbits; Rats; Species Specificity; Time Factors; Uranyl Nitrate; Urea; Warfarin

Topics: 1-Propanol; Acute Kidney Injury; Aged; Albumins; Antidepressive Agents; Antihypertensive Agents; Benzyl Compounds; Cephaloridine; Coumarins; Digitoxin; Diuretics; Drug Interactions; Ethacrynic Acid; Guanethidine; Guanidines; Heart; Heart Block; Heart Conduction System; Humans; Hypoglycemia; Hypotension; Kidney; Pancreas; Phenylbutazone; Salicylates; Sympathetic Nervous System; Tolbutamide; Warfarin

Topics: Acute Kidney Injury; Adult; Anticoagulants; Azathioprine; Biopsy; Cyclophosphamide; Dipyridamole; Female; Fibrin; Fluorescent Antibody Technique; Glomerular Filtration Rate; Glomerulonephritis; Heparin; Humans; Kidney Glomerulus; Male; Middle Aged; Prednisolone; Snake Venoms; Time Factors; Warfarin

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Anticoagulants; Australia; Azathioprine; Biopsy; Creatinine; Cyclophosphamide; Dipyridamole; Female; Fibrin; Glomerulonephritis; Heparin; Humans; Kidney; Kidney Glomerulus; Male; Middle Aged; Prednisolone; Prognosis; Renal Dialysis; Seasons; Steroids; Warfarin

Topics: Acute Kidney Injury; Aged; Anticoagulants; Hematoma; Hematuria; Hemoperitoneum; Heparin; Humans; Male; Retroperitoneal Space; Warfarin

Topics: Acute Kidney Injury; Adult; Aluminum Hydroxide; Amyloidosis; Barbiturates; Calcium; Cortisone; Humans; Magnesium; Male; Parasympatholytics; Phosphorus; Prednisone; Sarcoidosis; Splenectomy; Warfarin

Topics: Acute Kidney Injury; Arteriosclerosis; Cholesterol; Embolism, Fat; Gangrene; Humans; Hypertension; Male; Middle Aged; Pancreatitis; Toes; Warfarin