Anticoagulants and acute kidney injury: clinical and pathology considerations

Abstract

We have recently identified a new clinical syndrome in patients receiving warfarin for anticoagulation therapy. This syndrome has been named warfarin-related nephropathy (WRN), and patients with chronic kidney disease (CKD) appear to be particularly susceptible. WRN is defined as an acute increase in international normalized ratio (INR) to >3.0, followed by evidence of acute kidney injury (AKI) within 1 week of the INR increase. AKI was defined as a sustained increase in serum creatinine of greater than or equal to 0.3 mg/dL. The AKI cannot be explained by any other factors, and the kidney biopsy demonstrates extensive glomerular hemorrhage with tubular obstruction by red blood cells (RBCs). Beyond AKI, WRN is a significant risk factor for mortality within the first 2 months of diagnosis and it accelerates the progression of CKD. We demonstrated that 5/6 nephrectomy in rats is a suitable experimental model to study WRN. Animals treated with warfarin showed an increase in serum creatinine and morphologic findings in the kidney similar to those in humans with WRN. Our recent evidence suggests that novel oral anticoagulants may induce AKI. Diagnosis of WRN may be challenging for a renal pathologist. A few cases with suspected WRN and pathologic considerations are described.

Direct oral anticoagulant and AKI: apixaban-induced acute interstitial nephritis

“…Another case report found initiation of treatment with apixaban resulted in aggravation of pre-existing mild AKI 9. While these renal complications are treatable, prolonged diagnoses and initiation of treatment can lead to end-stage kidney disease and increased morbidity 10…”

应用动物模型探索肾脏疾病作用机制和潜在治疗靶点

“…The 5/6 nephrectomy was performed in Sprague Dawley rats, with animals allowed three weeks recovery from the surgery before warfarin treatment. Warfarin was given orally via drinking water, and warfarin dosage was based on rat weight ( Brodsky, 2014 ). Extensive glomerular hemorrhage and tubular obstruction can occur in rats after seven days administration of warfarin (0.4 mg/kg/d), as well as increased serum creatinine ( Brodsky, 2014 ; Ozcan et al, 2012 ).…”

“…Warfarin was given orally via drinking water, and warfarin dosage was based on rat weight ( Brodsky, 2014 ). Extensive glomerular hemorrhage and tubular obstruction can occur in rats after seven days administration of warfarin (0.4 mg/kg/d), as well as increased serum creatinine ( Brodsky, 2014 ; Ozcan et al, 2012 ). Besides, WRN can also induce AKI, accelerate CKD, and increase the mortality rate in warfarin-treated patients ( Brodsky et al, 2011 ).…”

Acenocoumarol as an alternative anticoagulant in a patient with warfarin‐related nephropathy

“…Though the definitive diagnosis of WRN is made by renal biopsy, presumptive diagnosis of WRN can be made before doing renal biopsy, as there is high risk of bleeding in patients taking anticoagulants. The presumptive diagnosis can made if there is an acute increase in international normalized ratio (INR) to >3.0, followed by evidence of acute kidney injury (AKI) within 1 week of the INR increase . Though INR >3 is required for presumptive diagnosis of WRN, there are also reports of WRN even at INR < 3 .…”