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

Abstract

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.

Keywords: Acute kidney injury; Anticoagulant-related nephropathy; Kidney biopsy.

Figure 1. Serum creatinine changes in association with apixaban treatment

Changes in serum creatinine level are shown by a solid line. Initiation of treatment with apixaban and kidney biopsy time are depicted by arrows. Hematuria prior and after apixaban therapy is shown as urinalysis (UA). Specific dates are depicted on the X axis, and the corresponding serum creatinine levels are shown above. HPF, high power field; RBC, red blood cell.

Figure 2. Light microscopy kidney biopsy findings (H&E stain)

(A) A single small segmental cellular crescent is noted in one out of 68 glomeruli with open capillary loops (×100). (B) Numerous occlusive red blood cell casts were seen in the tubules. Acute tubular necrosis is present (×100). (C) Red blood cells were filling Bowman’s space in some glomeruli (×200).

Figure 3. Immunofluorescence and electron microscopy findings

(A) Trace segmental granular staining in the mesangium was seen by direct immunofluorescence with an antibody to immunoglobulin A (fluorescein isothiocyanate [FITC], ×400). (B) Mild granular staining in the mesangium was seen by direct immunofluorescence with an antibody to C3 (FITC, ×400). (C) Occasional small electron dense deposits were seen in the mesangium by ultrastructural examination (×5,000). (D) Dysmorphic red blood cells in Bowman’s space were seen by electron microscopy. Of note, no deposits were seen in the glomerular basement membrane of the mesangium in this segment of the glomerulus (×4,000).