Anticoagulant-related Nephropathy Research Articles

WCN24-1802 Outcomes in patients with anticoagulant related nephropathy: from bad to worse

WCN24-1802 Outcomes in patients with anticoagulant related nephropathy: from bad to worse

Role of plasminogen activated inhibitor-1 in the pathogenesis of anticoagulant related nephropathy.

Anticoagulant related nephropathy (ARN) is the result of glomerular hemorrhage in patients on systemic anticoagulation therapy or underlying coagulopathy. Red blood cells (RBC) that passed through the glomerular filtration barrier form RBC casts in the tubules, increase oxidative stress and result in acute tubular necrosis (ATN). The mechanisms of ARN still not completely discovered. Plasminogen activator inhibitor-1 (PAI-1) plays a significant role in the maintenance of coagulation homeostasis. We developed an animal model to study ARN in 5/6 nephrectomy (5/6NE) rats. The aim of this study was to elucidate the role of PAI-1 in the ARN pathogenesis. 5/6NE rats were treated per os with warfarin (0.75 mg/kg/day) or dabigatran (150 mg/kg/day) alone or in combination with PAI-1 antagonist TM5441 (2.5, 5.0 and 10 mg/kg/day). TM5441 in a dose dependent manner ameliorated anticoagulant-induced increase in serum creatinine in 5/6NE rats. Anticoagulant-associated increase in hematuria was no affected by TM5441. The levels of reactive oxygen species (ROS) in the kidneys were in a dose-dependent manner decreased in 5/6NE rats treated with an anticoagulant and TM5441. Our data demonstrates that PAI-1 may reduce ARN by decreasing ROS in the kidneys. Glomerular hemorrhage is not affected by anti-PAI-1 treatment. These findings indicate that while symptoms of ARN can be reduced by PAI-1 inhibition, the main pathogenesis of ARN - glomerular hemorrhage - cannot be prevented.

Pitfalls in anticoagulant-related nephropathy.

Anticoagulant-related nephropathy (ARN) is a rare but important disease and often misdiagnosed. The hallmark of the diagnosis is acute kidney injury (AKI) superimposed on preexisting kidney disease due to anticoagulation-induced glomerular hemorrhage with histologic features of widespread tubular obstruction by red blood cells and red cell casts. As ARN is a diagnosis of exclusion only proven by renal biopsy, the diagnosis is often unlikely to be confirmed histologically because of fear of biopsy-related bleeding during anticoagulant therapy. Given the large differential diagnosis in AKI, diagnosing ARN remains a challenge for clinicians. A case report and the pitfalls related to diagnosis and management will be discussed in this paper.

Anticoagulant-Related Nephropathy in a Patient on Coumadin

Abstract Introduction/Objective Anticoagulant therapy is commonly used to prevent stroke and systemic embolism in patients with atrial fibrillation. However, it carries the risk of bleeding and can lead to serious complications such as anticoagulant-related nephropathy (ARN), a recently described entity characterized by hematuria and acute kidney injury. This report presents a case of a 79-year-old male with a history a patient with a history of atrial fibrillation on coumadin, highlighting the importance of monitoring for anticoagulant-related complications and the need for prompt diagnosis and management to prevent further renal damage. Methods/Case Report The kidney biopsy showed evidence of underlying hypertensive and diabetic nephropathy, with nodular and global glomerulosclerosis, moderate to marked interstitial fibrosis, and tubular atrophy along with many red cell casts of variable ages in the tubules indicative of anticoagulant-related nephropathy. Additionally, one glomerulus had a partial cellular crescent associated with a focus of blood clot, likely related to heavy hematuria. Patient is seronegative for ANCA. The immunofluorescence microscopy is non-contributory due to absence of glomerulus in the sample. Electron microscopy showed diffuse foot process effacement and microvillous transformation of podocytes, increased mesangial matrix, and thickened glomerular basement membranes, but no immune complex deposits. these ultrastructural features confirm the background diabetic nephropathy. Results (if a Case Study enter NA) NA Conclusion Anticoagulant-related nephropathy (ARN) is a rare but serious complication of anticoagulation therapy that can result in hematuria and acute kidney injury. Our case highlights the importance of monitoring for anticoagulant-related complications, especially in high-risk patients with multiple comorbidities. Prompt diagnosis and management of ARN is essential to prevent further renal damage. In this case, despite initial improvement with vitamin K therapy, the patient developed severe renal dysfunction requiring dialysis and renal biopsy. This emphasizes the need for increased awareness and early recognition of ARN in patients on anticoagulant therapy.

Double Insult: Secondary IgA and Anticoagulant-Related Nephropathy

Double Insult: Secondary IgA and Anticoagulant-Related Nephropathy

Correlation of Red Blood Cell Casts With Renal Dysfunction in Patients With Infection-Related Glomerulonephritis.

Infection-related glomerulonephritis (IRGN) usually manifests as a proliferative immune-complex glomerulonephritis. The degree of renal dysfunction at presentation can vary. Association with histologic features on kidney biopsy remains unknown. To study the correlation between renal function in IRGN at the time of biopsy and the severity of histologic features. Culture-proven IRGN cases at our facility were included and divided based on estimated glomerular filtration rate (eGFR) 15 ml/min/1.73 m2. Patients' demographic and pathologic findings were obtained from electronic medical records and kidney biopsy reports. In total, 104 cases were diagnosed with IRGN on biopsy (mean age, 55.6 ± 15.6 years; male, n = 79 [76%]; median eGFR, 14.5 mL/min/1.73 m2), and 51 of 104 showed eGFR <15 mL/min/1.73 m2. Among all the histologic features assessed, only percent tubules with red blood cell (RBC) casts showed statistical difference, being significantly higher in the lower-eGFR group (P = .004). Multivariable logistic regression analysis also showed that %tubules with RBC casts were associated with lower eGFR (odds ratio, 1.12; 95% CI, 1.01-1.24; P = .01). Patients with 5% or more RBC casts (n = 31) showed a lower eGFR (P = .02) and a higher %cellular crescent (P < .001) compared with those with less than 5% RBC casts. Patients with concomitant anticoagulant therapy (n = 11) showed higher percentages of RBC casts than those without anticoagulants (P = .02). Particular attention to the extent of RBC casts on kidney biopsy is recommended in patients with IRGN because these portend worse renal dysfunction, more so in patients requiring anticoagulation (including for hemodialysis) because they are especially vulnerable to developing anticoagulant-related nephropathy.

Clinical Outcomes in Patients With Biopsy Proven Anticoagulant-Related Nephropathy

Clinical Outcomes in Patients With Biopsy Proven Anticoagulant-Related Nephropathy

100 Anticoagulant-Related Nephropathy Associated With Atypical ANCA

100 Anticoagulant-Related Nephropathy Associated With Atypical ANCA

Research Letter: Is the 129S1/SvImJ Mouse Strain More Suitable to Study Anticoagulant-Related Nephropathy Than the C57BL/6 Strain?

We have previously demonstrated that excessive anticoagulation with warfarin or dabigatran may result in acute kidney injury with red blood cell (RBC) tubular casts in some patients with chronic kidney disease, and this condition was named anticoagulant-related nephropathy (ARN). 5/6 nephrectomy (5/6NE) rats treated with warfarin or dabigatran reproduce the main pathologic features of human ARN. We had reported that 5/6NE C57BL/6 mice only partially develop ARN with increased serum creatinine and hematuria but no RBC tubular casts in the kidney. The aim of this study was to investigate whether ARN can develop in 5/6NE 129S1/SvImJ mice. 5/6NE was performed in 129S1/SvImJ mice. Three weeks after 5/6NE, mice were treated with warfarin (1.0 and 1.5 mg/kg/day) or vehicle for 7 days. Serum creatinine, hematuria, and prothrombin time (PT) were monitored daily. Renal morphology was evaluated at the end of the studies. Treatment with warfarin resulted in PT elevation 2 to 3 folds from baseline (1.0 mg/kg/day warfarin) and 4 to 5 folds from baseline (1.5 mg/kg/day warfarin) by day 7. Serum creatinine and hematuria elevated by day 7 in a dose-dependent manner. Histologically, 2 of 8 (25%) 5/6NE mice had RBCs in the tubules, and there was acute tubular epithelial cell injury in all warfarin-treated 5/6NE 129S1/SvImJ mice. Our findings suggest that 129S1/SvImJ mouse strain is a more suitable murine model to study ARN than C57BL/6 mouse strain.

Warfarin Related Kidney Damage: A Confusing Case of Thrombophlebitis Masquerading as Infection.

Anticoagulant-related nephropathy (ARN) is a rare, newly recognized cause of acute kidney injury and significant but underdiagnosed complication of anticoagulation therapy. ARN occurs in patients taking oral anticoagulant therapy most often warfarin or a novel oral anticoagulant (NOAC). It is a potentially devastating disorder with serious renal consequences and increased all-cause mortality. Anticoagulant-related nephropathy presents as an acute kidney injury (AKI) in the setting of a supratherapeutic INR with profuse glomerular hemorrhage seen as renal tubules filled with red cells and red cell casts on renal biopsy. Being that millions of Americans are on warfarin, a thorough understanding and awareness of the clinical presentation, diagnosis, and therapeutic interventions are crucial to protecting the renal function, lowering all-cause mortality and optimizing treatment. Our goal is to provide education on a newly recognized form of AKI and significant but underdiagnosed complication of anticoagulation therapy.

Anticoagulant-related nephropathy induced by direct-acting oral anticoagulants: Clinical characteristics, treatments and outcomes

IntroductionThere is a scarcity of data on anticoagulation-related nephropathy (ARN) caused by direct-acting oral anticoagulants (DOACs) in recent years. Materials and methodsWe collected literatures on DOACs-induced ARN to October 1, 2022, without language restrictions for retrospective analysis. ResultsTwenty events were included with a median onset time of 28 days among which fourteen were caused by dabigatran. Patients accompanied by chronic kidney disease (85 %) seemed more easily to have an ARN. Clinical symptoms associated with ARN were mostly presented as hematuria and acute decline of renal function (100 %), then abnormal coagulation function (75 %) but only one with an INR over 3. Renal biopsies were performed in 14 patients, with thirteen showing occlusive intratubular red blood cell casts and ten showing acute tubular injury of varying intensity or even tubular necrosis. Extensive changes in interstitial compartment like hemorrhage, fibrosis or inflammation were also presented in eight biopsies. IgA nephropathy as a latent or undiagnosed disease was demonstrated in eight biopsies. Treatments of ARN were mainly supportive with all patients discontinuing DOACs and 35 % initiating dialysis for acute deterioration of renal function. Steroids were used in 9 patients with a severe ARN verified by biopsy. 60 % of patients did not recover baseline renal function and some even deteriorated. ConclusionsIn conclusion, DOACs-induced ARN is a rare but serious adverse reaction. A prompt diagnosis of ARN and supportive treatments are necessary for patients receiving DOACs concurrent with an acute renal injury.

Role of protease‐activated receptor‐1 (PAR‐1) in the glomerular filtration barrier integrity

Protease‐activated receptors (PAR) play an important role in the regulation of cellular function by the coagulation system, and they are activated by thrombin. PAR‐1 is expressed in both endothelial cells and podocytes in the kidney. The role of PAR1 in the maintenance of the glomerular filtration barrier is not clear. Anticoagulant‐related nephropathy (ARN) is a kidney disease with glomerular hematuria and red blood cell tubular casts. We validated 5/6 nephrectomy (5/6NE) in rats as a model of ARN and had demonstrated that direct thrombin inhibitor (dabigatran) induces ARN. The aim of this study was to investigate the role of PAR‐1 in the ARN pathogenesis. 5/6NE rats were treated with dabigatran (150 mg/kg/day), PAR‐1 inhibitor SCH79797 (1 and 3 mg/kg/day) and PAR‐1 agonist TFLLR‐NH2 (0.25 and 0.50 µmol/kg/day) for 7 days. Serum creatinine and hematuria were assessed daily. Kidney morphology was evaluated at the end of the study. In 5/6NE rats treated with either dabigatran or combination with a PAR‐1 modulator, there was an elevation in serum creatinine, glomerular hematuria, red blood casts in the tubules, and acute tubular epithelial cell injury. Interestingly, both PAR‐1 modulators in a dose‐depended manner had similar effects on the serum creatinine levels and hematuria as those of dabigatran. Dabigatran‐induced increase in the systolic blood pressure was not affected by PAR‐1 modulators. In conclusion, the normal function of PAR‐1 is crucial to maintain the glomerular filtration barrier integrity. Either activation or blockage of PAR‐1 leads to glomerular hematuria and subsequent acute tubular epithelial cell injury.

A Case of Anticoagulant-related Nephropathy

A Case of Anticoagulant-related Nephropathy

Acenocoumarol-Induced Anticoagulant–Related Nephropathy with Newly Diagnosed IgA Nephropathy: a Repeat Biopsy Case Report

Anticoagulant-related nephropathy (ARN) is an underestimated cause of acute kidney injury (AKI) with poor renal and overall prognosis. Pathogenesis is not fully elucidated yet, although AKI is probably resulting from glomerular hemorrhage and most commonly has been described in patients with glomerular lesions, that alter the glomerular permeability, and conditions with glomerular hyperfiltration. Herein, we describe a case with a 58-year-old man who presented with macroscopic hematuria and AKI, and recently taking acenocoumarol for aortic valve replacement. The first renal biopsy showed red cell casts in the renal tubules, one glomerular crescent formation in the glomeruli with mild immunoglobulin A deposition, and severe interstitial inflammation. Based on these findings, the patient was diagnosed with acenocoumarol-induced ARN with newly diagnosed IgA nephropathy and switched to tinzaparin with a short course of corticosteroids. Renal improvement in ARN is usually partial and is delayed, as confirmed by a second biopsy in our patient after 6 months.

Possible influence of atheroembolism in anticoagulant-related nephropathy: a nephrology image.

Possible influence of atheroembolism in anticoagulant-related nephropathy: a nephrology image.

Anticoagulant-related nephropathy: Focus on novel agents. A review.

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.

Warfarin-Related Nephropathy Manifested as Diffuse Mesangial Proliferative Glomerulonephritis

Warfarin is associated with anticoagulant-related nephropathy (ARN), one of the potential side effects. This is evidenced by a progressively increasing number of detected cases of deterioration in the kidney function even in patients with normal baseline function (GFR {glomerular filtration rate}) in addition to the chronic kidney disease (CKD) patients who are already vulnerable to ARN. There has been a clinical correlation in a rapid decline of kidney function and international normalized ratio (INR) levels of greater than three. ARN is a significant but underdiagnosed complication of anticoagulation that is associated with increased renal morbidity and all-cause mortality. We want to emphasize the importance of monitoring kidney function regularly and adjusting the appropriate doses of warfarin. We present a case of a 57-year-old female who was on warfarin for the mechanical aortic valve, presented with acute kidney injury and supratherapeutic INR. Her renal biopsy showed diffuse mesangial proliferative glomerulonephritis.

Case report: rivaroxaban related nephropathy

The characteristics of direct oral anticoagulants (DOACs) make them more appealing for prevention of thromboembolic events than vitamin K antagonists (VKA). Despite that, both classes have been a recognized as a cause of anticoagulant related nephropathy (ARN). Herein we describe a case of a 72-year-old man, with chronic kidney disease (CKD), medicated with rivaroxaban, who presented with acute kidney injury (AKI) and microscopic hematuria. The kidney biopsy revealed anticoagulant related-nephropathy. Rivaroxaban was suspended, the patient showed improvement of renal function and apixaban was prescribed. This case emphasizes the need for careful monitoring of serum creatinine when these drugs are prescribed, especially in high risk groups.

Frequently Missed, Never Dismissed: Anticoagulant-Related Nephropathy&amp;lt;br/&amp;gt;—Case Presentation and Review of the Literature

We reported here a case of anticoagulant-related nephropathy (ARN) in an elderly patient with background history of chronic kidney disease (CKD-stage 4, with an estimated glomerular filtration rate (eGFR) of <24 ml/min). He presented with an acute kidney injury on background of chronic kidney disease (AKI/CKD) with eGFR of 9 ml/min and serum creatinine of 6.0 mg/dl.

Anticoagulant-Related Nephropathy Induced By Direct-Acting Oral Anticoagulants: Clinical Characteristics, Treatments and Outcomes

Anticoagulant-Related Nephropathy Induced By Direct-Acting Oral Anticoagulants: Clinical Characteristics, Treatments and Outcomes