Warfarin-related nephropathy in a patient with mild IgA nephropathy on dabigatran and aspirin

Abstract

Dabigatran is a direct thrombin inhibitor used as an alternative to warfarin for long-term anticoagulation. We describe a patient who developed acute kidney injury (AKI) in the setting of warfarin conversion to dabigatran, and a renal biopsy demonstrating acute tubular injury. Although the patient had undiagnosed IgA nephropathy that may have predisposed him to bleeding, AKI was due to heme-associated tubular injury. We propose that severe hematuria in patients with underlying glomerular pathology treated with either dabigatran or warfarin may lead to toxic tubular injury through the accumulation of heme-proteins.

Keywords: acute kidney injury; acute tubular necrosis; dabigatran.

Figures

Fig. 1.

(A) Diffuse acute tubular injury with RBC casts and cytoplasmic reabsorption droplets (arrow) (H&E 400×). (B) Glomerulus with increased mesangial cellularity (H&E 400×). (C) IF stain for IgA with strong mesangial staining pattern (200×); (D) EM with mesangial immune complex deposits (arrow; ×8000). Basement membranes with normal thickness of 230 ± 60 nm; (E) EM of tubular epithelium with cytoplasmic reabsorption droplets containing heme proteins (arrow; 13 000×). (F) Immunohistochemistry stain for CD163 (×400).

Fig. 2.

Injury mechanisms of heme toxicity: 1. Heme-proteins increase endothelin-1 levels, causing vasoconstriction and ischemic injury. 2. Heme-proteins stimulate inflammatory infiltrate to the interstitium. 3. The tetrapyrrole heme molecule induces lysosomal overload and lysosomal cell injury. 4. Heme-proteins induce apoptosis and oxygen-radical formation. 5. Heme-proteins cause injury through oxidative damage to the mitochondria. 6. Heme augments ischemia-induced peroxidation.