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.

Keywords: Acute kidney injury; Anticoagulation therapy; Chronic kidney disease; Warfarin-related nephropathy.

Figure 1

Light microscopy, immunofluorescence, and electron microscopy in a patient with suspicious warfarin-related nephropathy (WRN) (Case 1). (A) Light microscopy shows numerous red blood cell (RBC) casts in the tubules and acute tubular necrosis. Hematoxylin and Eosin, magnification 40×. (B) Glomeruli are unremarkable by light microscopy. Periodic acid–Schiff stain, magnification 200×. (C) Direct immunofluorescence with an antibody to IgG shows mild mesangial staining. Magnification 200×. (D) Electron microscopy shows scattered mesangial electron-dense immune-type deposits (arrow). Magnification 10,000×.

Figur 2

Light microscopy in a patient with suspicious warfarin-related nephropathy (WRN) (Case 2). Light microscopy shows numerous red blood cell (RBC) casts in the tubules and acute tubular necrosis. Hematoxylin and Eosin, magnification 200×.