Warfarin-related nephropathy induced by three different vitamin K antagonists: analysis of 13 biopsy-proven cases

Abstract

Background: Acute kidney injury (AKI) with renal tubular obstruction by red blood cell casts (RBCC) has been described in patients treated with warfarin and is known as warfarin-related nephropathy (WRN). Methods: To determine whether other vitamin K antagonists (VKA) cause WRN, we retrospectively collected and analyzed the clinical and histological data of 13 patients treated with different VKA (seven with fluindione, four with warfarin and two with acenocoumarol) in seven French hospitals. Results: They all developed gross hematuria following overanticoagulation complicated by severe AKI (median serum creatinine concentration = 693 μmol/L). Histological analysis of the kidney biopsies highlighted the presence of intratubular RBCC and acute tubular necrosis in all patients and of an underlying kidney disease in 12 patients. WRN was suspected in patients treated with warfarin; however, the initial diagnosis was incorrect in six of the nine patients treated with other VKA. Nine patients progressed to chronic kidney disease, one fully recovered renal function, two died and one still needs dialysis. Conclusions: This is the first report of AKI caused by fluindione. In agreement with the recent publication on AKI in two patients treated with dabigatran, we suggest that the term 'anticoagulant-related nephropathy' is more appropriate than WRN. Gross hematuria in patients with an underlying kidney disease and treated with VKA requires rapid control of the international normalized ratio and renal function monitoring.

Keywords: acute kidney injury; drug nephrotoxicity; renal biopsy; vitamin k antagonists; warfarin-related nephropathy.

Fig. 1

Different lesions observed in kidney biopsies from patients with AKI. (A) Masson’s trichrome staining showing acute tubular injury (arrows) associated with tubular obstruction by red blood cell casts (arrowheads) (magnification ×200). (B) Masson’s trichrome staining showing red blood cells (arrows) in the Bowman’s space (magnification ×200).

Fig. 2

Renal function changes in the 13 patients during the follow-up after AKI.

Fig. 3

INR value and SC concentration changes over time in the two patients (#4 and #10) with AKI recurrence.