Anticoagulant-related Nephropathy Research Articles

AKI Associated with Anticoagulant-Related Nephropathy in a Newly Diagnosed IgA Nephropathy

AKI Associated with Anticoagulant-Related Nephropathy in a Newly Diagnosed IgA Nephropathy

Case Report of Rivaroxaban-Induced Anticoagulant-Related Nephropathy

Case Report of Rivaroxaban-Induced Anticoagulant-Related Nephropathy

MO168MANAGEMENT OF ANTICOAGULANT RELATED NEPHROPATHY: SLOVENIAN CASE SERIES AND REVIEW OF CURRENT KNOWLEDGE

Abstract Background and Aims Anticoagulant-related nephropathy is a recently recognized form of acute kidney injury associated with previously underdiagnosed kidney damage in addition to (usually) excessive anticoagulation. It occurs in patients receiving warfarin as well as those receiving direct oral anticoagulants. Method We collected and analyzed cases of Slovenian patients with pathohistologically documented anticoagulant-related nephropathy associated with all types of anticoagulant treatment from the first case in 2014 to 2020. We also performed an analysis of previously documented cases of anticoagulant-related nephropathy in the global literature (PubMed) in the period from their first mention until recently. Results In Slovenia, 13 patients with anticoagulant-related nephropathy have been histologically verified so far. All patients were diagnosed with concomitant underlying renal disease, and 80% had IgA nephropathy, which was disproportionately mild according to the degree of renal function impairment. After supportive measures and reversal of excessive anticoagulation, 8 of 13 patients were further treated with corticosteroids, resulting in significant improvement in renal function. During the follow-up period, a total of one steroid-treated patient died due to infectious complications and one patient progressed to end-stage renal failure. In the worldwide literature, we found 46 case reports or case series of patients with anticoagulant-related nephropathy. Failure of restitution of renal function with the need for maintenance dialysis was reported much more frequently compared to the results of our cohort (up to 67% vs. 8.3%) Conclusion To our knowledge, the Slovenian cohort of patients with histologically established anticoagulant-related nephropathy is the largest reported series to date that received corticosteroid therapy in addition to conservative measures. Our results indicate that steroids have a beneficial effect, likely exerted via suppression of hemoglobin-associated oxidative stress and inflammation. However, considering the polimorbidity of these patients, the benefit of additional steroid therapy must be weighed against the potential risks of side effects, especially life-threatening infections.

MO378WHAT LIES BENEATH ANTICOAGULATION-RELATED ACUTE KIDNEY INJURY

Abstract Background and Aims Acute kidney injury (AKI) secondary to glomerular hemorrhage in the context of overanticoagulation, commonly known as anticoagulant-related nephropathy (ARN), is a relatively novel recognized entity. Preexisting or underlying kidney disease seems to be a predisposing factor; however, few studies have described histologic findings in patients with ARN. We aimed to examine underlying kidney pathology in patients on oral anticoagulation who presented an episode of AKI with hematuria in whom a kidney biopsy was performed. Method Spanish retrospective observational multicenter case study in patients treated with oral anticoagulants who developed macroscopic or intense hematuria followed by AKI. Only patients with available kidney biopsy specimens were included. Histologic findings and clinical data throughout follow-up were analyzed. The main outcome was to describe pathologic findings in kidney biopsy specimens of patients with clinical suspicion of ARN. The secondary outcome was to assess kidney outcomes during follow-up. Results Twenty-four patients were included with a median age of 76 years (interquartile range [IQR] 64-81) and a follow-up period of 10.1 (IQR 1.3-41.1) months. 79% were male, 22 (91%) had hypertension and 9 (37%) were diabetic. Most cases (91%) were on anticoagulation with vitamin K antagonists. At admission, 87% of cases presented gross hematuria with a median serum creatinine (SCr) of 4.2 mg/dl and a median INR of 2.3. During follow-up, median highest (peak) SCr was 6.3 mg/dl and 11 (45%) patients required acute dialysis. Kidney biopsy showed that all patients except one had an underlying nephropathy (confirmed IgA nephropathy in 16 [66.7%], probable IgA nephropathy in 2, diabetic nephropathy in 3, nephrosclerosis in 1, and idiopathic nodular glomerulosclerosis in 1). Tubules filled with red cells and red cell casts were observed in 66.7% of the cases and acute tubular necrosis in 70.8%. Management included anticoagulation withdrawal in 14 cases (58.3%) and immunosuppressive treatment with corticosteroids (n = 17 [70.8%]) and mycophenolic acid (n = 5 [20.8%]). At 12 weeks after discharge, 11 patients had >50% decrease in SCr (with respect to peak SCr), 6 had <50% decrease and 5 were on chronic dialysis. Conclusion IgA nephropathy was the most common underlying kidney disease in our biopsy-proven series of ARN, in which a significant percentage of patients did not achieve kidney function recovery.

POS-058 WHAT LIES BENEATH ANTICOAGULATION-RELATED ACUTE KIDNEY INJURY

Acute kidney injury (AKI) secondary to glomerular hemorrhage in the context of overanticoagulation, commonly known as anticoagulant-related nephropathy (ARN), is a relatively novel recognized entity. Preexisting or underlying kidney disease seems to be a predisposing factor; however, few studies have described histologic findings in patients with ARN. We aimed to examine underlying kidney pathology in patients on oral anticoagulation who presented an episode of AKI with hematuria in whom a kidney biopsy was performed.

Management of Anticoagulant-Related Nephropathy: A Single Center Experience.

Background: Anticoagulant-related nephropathy (ARN) is a form of acute kidney injury that mainly occurs in patients with previously unrecognized glomerular disease in addition to excessive anticoagulation. Since a renal biopsy is not performed in most cases, the diagnosis is often presumptive. Methods: Here, we present the characteristics of a national Slovenian patient cohort with histologically verified ARN, from the first case in 2014 to December 2020, and a review of the current literature (Pubmed database). Results: In Slovenia, ARN has been detected in 13 patients, seven of whom were treated with coumarins, and others with direct oral anticoagulants. In seven patients, ARN appeared after excessive anticoagulation. As many as 11 patients had underlying IgA nephropathy. Similar to the global data presented here, the pathohistological impairment associated with pre-existing glomerulopathy was mild and disproportionate to the degree of functional renal impairment. The majority of our patients with ARN experienced severe deterioration of renal function associated with histological signs of accompanying acute tubular injury, interstitial edema, and occlusive red blood cell casts. These patients were treated with corticosteroids, which (in addition to supportive treatment and discontinuation of the anticoagulant drug) led to a further improvement in renal function. Conclusions: Anticoagulant therapy combined with a pre-existing glomerular injury may lead to ARN. In addition to discontinuation of the anticoagulant and supportive care, corticosteroids, which are currently listed in only a few cases in the world literature, may have a positive influence on the course of treatment. However, the benefits of steroid treatment must be weighed against the risk of complications, especially life-threatening infections.

Anticoagulant Related Nephropathy Only Partially Develops in C57BL/6 Mice: Hematuria Is Not Accompanied by Red Blood Cell Casts in the Kidney.

Anticoagulant-related nephropathy (ARN) may develop in patients that are on anticoagulation therapy. Rats with 5/6 nephrectomy treated with different anticoagulants showed acute kidney injury (AKI) and red blood cell (RBC) casts in the tubules similar to ARN in humans. The aim of the current study was to investigate the feasibility of inducing ARN in mice. C57BL/6 5/6 nephrectomy mice were treated with warfarin and dabigatran 3 weeks after ablative surgery for 7 days. Two doses of each anticoagulant were used. All anticoagulants resulted in serum creatinine and hematuria increase. Mortality was 63% in 5.0 mg/kg/day of warfarin but only 13% in 2.5 mg/kg/day of warfarin or in 400 mg/kg/day of dabigatran and 0% in 200 mg/kg/day of dabigatran. In spite of increasing hematuria, RBC tubular casts were not seen in mice treated with any anticoagulant. The 5/6 nephrectomy murine model in C57BL/6 mice only partially reproduced ARN in terms of increasing serum creatinine and hematuria, but there were no RBC tubular casts in the remnant kidney.

Role of glomerular filtration rate-modifying drugs in the development of anticoagulant-related nephropathy.

IntroductionAnticoagulant‐related nephropathy (ARN), that was described in humans first as warfarin‐related nephropathy, is characterized by acute kidney injury and red blood cell (RBC) tubular casts in the kidney. 5/6 nephrectomy (5/7NE) rats treated with warfarin or dabigatran show changes in kidney function and morphology that are similar to human disease. The role of glomerular filtration rate (GFR) in the pathogenesis of ARN is not clear. The aim of these studies was to elucidate the role of GFR in the pathogenesis of dabigatran‐induced ARN in 5/6NE rats.Methods5/6NE rats were treated per os with 150 mg/kg/day dabigatran alone or with drugs that lower (enalapril, 1.5 mg/kg/day) or increase (albuterol, 4.0 mg/kg/day) GFR for 7 days. Changes in coagulation and kidney function were recorded daily. Kidney morphology was evaluated on day 7 after the treatment.ResultsDabigatran resulted in activated partial thromboplastin time increase that was not affected by GFR‐modifying drugs. Blood pressure was significantly lower in 5/6NE rats treated with enalapril and dabigatran as compared to dabigatran alone. The GFR was decreased by 35% in enalapril/dabigatran‐ and increased by 26% in albuterol/dabigatran‐treated animals. There were no changes in serum creatinine, hematuria or urinary kidney injury molecule (KIM‐1) levels when GFR‐modifying drugs were added to dabigatran. All dabigatran‐treated animals had RBC casts in the kidney regardless of the GFR modification.ConclusionsGFR does not play a significant role in the dabigatran‐induced acute kidney injury in 5/6 nephrectomy model in rats. Based in these data, modification of GFR in patients with ARN is not warranted.

Differences in risk factors for anticoagulant-related nephropathy between warfarin and direct oral anticoagulants: Analysis of the Japanese adverse drug event report database.

Limited information is available on anticoagulant-related nephropathy (ARN). We therefore reviewed the Japanese Adverse Drug Event Report database to investigate kidney injury (KI) in patients administered warfarin or direct oral anticoagulants (DOACs) and sought to clarify the risk factors for ARN. KI risk in warfarin users was associated with male sex (odds ratio [OR], 1.70; 95% confidence interval [CI], 1.35-2.13; P<.01) and age ≥80years (OR, 1.35; 95% CI, 1.07-1.72; P=.01). KI risk in DOAC users was associated with body weight ≥80kg (OR, 1.60; 95% CI, 1.01-2.53; P=.04) and use of dabigatran (OR, 1.61; 95% CI, 1.09-2.37; P<.01). Our findings suggest that risk factors for ARN differ between warfarin and DOACs and that these risk factors may be associated with bleeding risk. Therefore, the risk of ARN may be decreased by better managing bleeding risk in patients taking anticoagulants.

Role of Glomerular Filtration Rate (GFR)-Modifying Drugs in Prevention of Anticoagulant-Related Nephropathy (ARN)

Role of Glomerular Filtration Rate (GFR)-Modifying Drugs in Prevention of Anticoagulant-Related Nephropathy (ARN)

Anticoagulation related nephropathy

Background :Anticoagulation related nephropathy (ARN) is an under diagnosed complication of anticoagulation that is associated with increased renal morbidity and mortality.While warfarin has been in use since 1954, its harmful effects on the kidneys have only recently been fully recognized. ARN is clinically defined as acute kidney injury (AKI) without obvious aetiology in the setting of over anticoagulation .When it is caused by warfarin, it is often associated with supra therapeutic International Normalized Ratio (INR) (more than 3.0) .AIM: this work aimed to early detection of ARN and how to manage it. Patients and methods: This study was carried out in internal medicine department of Benha University Hospitals, where 50 patients on oral anticoagulation suffered from acute kidney injury were selected and subjected to careful history , clinical examination and laboratory investigation after taking their written consents from march 2019 to march 2020. Results: From the 50 patients ARN was observed in 30% of patients (15 patients) .80% of patients were on warfarin and 20%of patients were on dapigatran. 34% of patients were hypertensive, 56% of patients were chronic kidney disease (CKD) and 40% of patients were diabetic .At the start of the study serum creatinine was 1.5± o.5 mg/dl and mean INR was 2.4±0.6 and after starting oral anticoagulants (OACs) mean INR increased to 6.3±1.8 and serum creatinine increased to 2.6±o.8 mg/dl at the first month of follow up then by controlling INR to 2.8±0.4 at the second month serum creatinine decreased to 2± 0.6 mg/dl. Conclusion: ANR should be suspected in any patients with over anticoagulation and increased serum creatinine and this need rapid intervention to reverse renal injury.

ANTICOAGULANT-RELATED NEPHROPATHY COMPLICATED BY HEPATORENAL SYNDROME FROM LUPOID HEPATITIS

Anticoagulant related nephropathy (ARN) is a newly recognized phenomenon. ARN is defined as over anticoagulation mostly associated with supratherapeutic INRs from warfarin leading to bleeding into the glomeruli. The diagnosis is confirmed with a kidney biopsy, which will show renal tubules filled

SAT-154 Anticoagulants and the kidney: 10 years of clinical and experimental experience

Ten years ago we reported a case of acute kidney injury (AKI) with occlusive red blood cell (RBC) tubular casts in a patient on warfarin therapy, who had high international normalized ratio (INR). We termed this condition warfarin related nephropathy (WRN). Later, we and others demonstrated that WRN is a part of the broader syndrome, when patients on other anticoagulants may develop AKI. This new syndrome is referred nowadays as anticoagulant related nephropathy (ARN). We developed an animal model that reproduces the main histologic findings of ARN in humans. Renal pathology database was searched for kidney biopsies from patients on anticoagulant therapy. Cases with acute kidney injury were analyzed. Rtas were used to create 5/6 n4phrectomy model. Based on our renal pathology database, among 8636 native kidney biopsies reviewed at our institution, there were 47 (0.54 %) patients in whom deterioration in the kidney function could not be explained by kidney biopsy findings alone if anticoagulation was not taken into the equation. Thirty five of those patients (74%) were on warfarin therapy, five (11%) were on anti-platelet medications (including two on heparin, two on enoxaparin and one on Plavix/aspirin) and one (2%) on Factor Xa inhibitor (apixaban). Six (13%) did not have records of anticoagulation therapy, but they had acute coagulopathy (such as disseminated intravascular coagulation syndrome) at the time of deterioration of kidney function and their biopsy findings suggested of ARN. In addition to acute tubular necrosis (ATN) and numerous RBC casts, these patients had underlying glomerular changes, but the severity of that glomerular disease was out of proportion to the number of RBC casts and/or hematuria in these patients. Among these glomerular changes, the most common was mild glomerular immune complex deposits without significant proliferative lesions (23 cases, 49%), followed by mild focal pauci-immune crescentic glomerulonephritis (7 cases, 15%), diabetic glomerulosclerosis (5 cases, 11%) and focal segmental glomerular sclerosis (FSGS, 5 cases, 11%). We demonstrated that 5/6 nephrectomy in rats is a suitable models to study ARN. Thus, 5/6 nephrectomy rats had increase in serum creatinine and RBC tubular casts in the kidney when treated with high dose of warfarin or dabigatran (direct thrombin inhibitor). We demonstrated that the mechanisms of ARN include oxidative stress that plays a significant role in the acute tubular injury, but not in the glomerular filtration barrier injury. Anticoagulant-treated animals developed hypertension with more pronounced increase in the systolic blood pressure than in diastolic blood pressure. ARN is an uncommon diagnosis in renal pathology practice, but it should be considered when there is a disproportion between the severity of glomerular changes and the number of RBC casts and/or hematuria in a kidney biopsy in patients on anticoagulant therapy or who presented with acute coagulopathy. The glomerular changes in patients with suspected ARN are insufficient to explain the occurrence of substantial blood in tubules. Animal model of 5/6 nephrectomy in rats reproduces the main clinical and pathologic features of ARN.

Anticoagulant-Related Nephropathy in Kidney Biopsy: A Single-Center Report of 41 Cases

Rationale & ObjectiveIn 2009, the first case of acute kidney injury and occlusive red blood cell (RBC) tubular casts associated with a high international normalized ratio in a patient receiving warfarin was identified. This entity, named warfarin-related nephropathy, was later renamed anticoagulant-related nephropathy (ARN) after similar cases with other anticoagulants were described. We provide our 10-year experience with ARN based on a single-center kidney biopsy laboratory.Study DesignThe kidney pathology database at the Ohio State University Wexner Medical Center (OSUWMC) was searched for native kidney biopsy cases consistent with ARN. Clinical data were obtained from patient medical records.Setting & ParticipantsNative kidney biopsies evaluated between January 1, 2009, and December 31, 2017 at OSUWMC.ResultsAmong 8,636 native kidney biopsies reviewed at the OSUWMC, there were 41 (0.5%) patients for whom deterioration in kidney function could not be explained by kidney biopsy findings alone if anticoagulation was not considered. There were 63% men and 95% were white; average age was 62 ± 14 years. Most were on warfarin therapy (N = 28), although cases were also attributed to direct-acting anticoagulants (N = 2), antiplatelet medications (N = 1), heparin or enoxaparin (N = 4), and disseminated intravascular coagulopathy (N = 6). Morphologically, there was acute tubular necrosis and RBC casts. The majority of biopsies had an underlying glomerular disease and many patients had positive serologic test results. In all these cases, the severity of kidney failure, RBC tubular casts, and hematuria were disproportionate to glomerular morphologic changes.LimitationsSelection bias in the decision to perform a kidney biopsy.ConclusionsARN is an uncommon diagnosis in kidney pathology practice, but it should be considered when the number of RBC tubular casts is disproportionate to the severity of glomerular changes in a kidney biopsy in patients either receiving anticoagulation therapy or who presented with acute coagulopathy. Our data suggest that anticoagulation aggravates underlying glomerular diseases rather than directly affecting the glomerular filtration barrier.

Anticoagulant-related nephropathy: systematic review and meta-analysis.

BackgroundThe aim of this study was to report the prevalence and mortality associated with anticoagulant-related nephropathy (ARN) through a systematic review of the literature. MethodsElectronic searches were conducted in the Medline and EMBASE databases, and manual searches were performed in the reference lists of the identified studies. The studies were selected by two independent researchers, first by evaluating the titles and abstracts and then by reading the complete texts of the identified studies. Case series, cross-sectional studies, cohort studies and case–control studies reporting the prevalence and factors associated with ARN were selected. The methodological quality was assessed using the Newcastle–Ottawa scale. Meta-analyses of the prevalence of ARN and 5-year mortality using the random effects model were performed when possible. Heterogeneity was assessed using the I2 statistic.ResultsFive studies were included. Prevalence of ARN ranged from 19% to 63% among the four included cohort studies. Meta-analysis of these resulted in high heterogeneity [I2 96%, summary effect 31%; 95% confidence interval (CI) 22–42%]. Subgroup meta-analysis yielded an ARN prevalence of 20% among studies that included patients with fewer comorbidities (I2 12%; 95% CI 19–22%). In a direct comparison, meta-analysis of the 5-year mortality rate between anticoagulated patients who had experienced ARN and anticoagulated patients without ARN, patients with ARN were 91% more likely to die (risk ratio = 1.91; 95% CI 1.22–3; I2 87%). Risk factors for ARN that were reported in the literature included initial excessive anticoagulation, chronic kidney disease, age, diabetes, hypertension, cardiovascular disease and heart failure.ConclusionsARN studies are scarce and heterogeneous, and present significant methodological limitations. The high prevalence of ARN reported herein suggests that this entity is underdiagnosed in clinical practice. Mortality in patients with ARN seems to be high compared with patients without this condition in observational studies.

Vitamin K antagonists and changes in glomerular filtration rate in patients with atrial fibrillation

Kidney injury with renal tubular obstruction by red blood cell casts has been described in patients treated with vitamin K antagonist (VKA) and is known as anticoagulant-related nephropathy. Therefore, instable INR might play a role in favoring anticoagulant-related nephropathy. We investigated the relationship of VKA use and estimated glomerular filtration rate (eGFR) evolution in AF patients. Patients diagnosed with AF in a four-hospital institution between 2000 and 2010 were identified. Renal function was evaluated using eGFR evolution in mL/min/1.73 m 2 /year. Risk factors for worsening renal function were investigated with multiple regression analysis. Two thousand six hundred and twenty-two patients had AF and serum creatinine data, with 10,894 patient-years of follow-up (FU). VKA was prescribed in 1580 (66%) patients, antiplatelet therapy for 473 (20%) and no antithrombotic treatment for 351 (14%). Non-VKA oral anticoagulants were not yet available. Mean eGFR evolution during follow-up was −1.91 mL/’/1.73 m 2 /year (median −1.26, interquartile range 6.30). Overall, patients with VKA use had similar eGFR evolution compared to non-users (−1.9 vs. −1.8 mL/’/1.73 m 2 /year, P = 0.77) and VKA use was not a predictor of eGFR evolution. Among patients with VKA use, those with labile INR ( n = 60, 4%), had a similar eGFR evolution than those with no labile INR (−2.7 vs. −1.9 mL/’/1.73 m 2 /year, P = 0.49). Finally, patients with VKA use with SAMe-TT2R2 score > 2 ( n = 293, 19%) had a similar eGFR evolution than those with SAMe-TT2R2 score ≤ 2 (−2.6 vs. −1.7 mL/’/1.73 m 2 /year, P = 0.20). We found that AF patients with VKA use did not have a worse eGFR evolution during FU than those not treated with oral anticoagulation. Patients treated with VKA with labile INR or likely to have poor anticoagulation control neither had a worse eGFR evolution. These Results suggest that instable INR might not be the main determinant of anticoagulant-related nephropathy.

Breadth of complications of long-term oral anticoagulant care.

The majority of patients with venous thromboembolism (VTE) have a considerable long-term risk of recurrence and may require extended duration of anticoagulant treatment after the initial 3 to 6 months. The decision to extend treatment is based not only on the individual risk of recurrence, but should also consider the potential complications associated with anticoagulation, taking into account that anticoagulant drugs are among the drugs most frequently associated with hospital admission due to adverse drug reactions. The most feared complication of oral anticoagulants is bleeding, which in some cases may be fatal or may affect critical organs. Case-fatality rates of bleeding have been reported to be ∼3 times higher than case-fatality rates of recurrent VTE. Even when nonserious, bleeding may require medical intervention and/or may impact on patient quality of life or working activity. Factors associated with bleeding during anticoagulant treatment include, among others, advanced age, cancer, renal or liver insufficiency, or concomitant antithrombotic drugs, but no bleeding risk score is sufficiently accurate for use in clinical practice. Not uncommonly, bleeding occurs as a complication of trauma or medically invasive procedures. Nonbleeding complications associated with oral anticoagulants are unusual, and their relevance is extremely uncertain, and include vascular calcification, anticoagulation-related nephropathy, and osteoporosis. Finally, because VTE not uncommonly affects young individuals and the mean age of the population is ∼60 years, the costs associated with extended anticoagulation should not be forgotten. The costs of the drugs need to be balanced against health outcome costs associated with both recurrent VTE and bleeding.

Anticoagulant-Related Nephropathy.

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 post hoc analyses of three pivotal anticoagulation trials and three retrospective analyses of large clinical databases. Taken together, these analyses suggest that ARN is not a rare occurrence in the anticoagulated patient with atrial fibrillation. However, much work needs to be done to understand the condition, particularly prospective studies, to avoid the biases inherent in post hoc and retrospective analyses. Finally, we provide recommendations regarding the diagnosis and management of ARN on the basis of the best information available.

Incidence and risk factors for acute kidney injury in patients with excessive anticoagulation on warfarin: a retrospective study.

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 > 26.5µmol/L within 7-14days 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.

Acute kidney injury aggravated by treatment initiation with apixaban: Another twist of anticoagulant-related nephropathy.

Anticoagulant-related nephropathy (ARN) was initially described in patients on warfarin (as warfarin-related nephropathy) and recently in those using dabigatran. Herein, we report clinical history and kidney biopsy findings in a patient on apixaban (Eliquis). Initiation of treatment with apixaban resulted in aggravation of preexisting mild acute kidney injury (AKI). A few days after apixaban therapy, the patient became oligoanuric, and kidney biopsy showed severe acute tubular necrosis with numerous occlusive red blood cell casts. Only one out of 68 glomeruli with open capillary loops had small segmental cellular crescent. Therefore, there was major discrepancy between the degree of glomerular injury and the glomerular hematuria. Considering that the onset of this AKI was associated with apixaban treatment initiation, we propose that this patient had ARN associated with factor Xa inhibitor (apixaban), which has not previously been described. Monitoring of kidney function is recommended after initiation of anticoagulant therapy.