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.

Impact of Altered Intestinal Microbiota on Chronic Kidney Disease Progression

“…More recently, more rapid CKD progression has been described in individuals anticoagulated with warfarin than in users of direct anticoagulants [ 98 ]. Thus, while macroscopic haematuria–associated AKI has been observed with any oral anticoagulant [ 99 , 100 ], drugs targeting vitamin K appear to increase the risk of CKD progression. Whether this is related to a nephroprotective action of vitamin K, the more frequent over coagulation episodes with warfarin or nephroprotective effects of direct anticoagulants related to factor Xa inhibition remains to be clarified.…”

Anticoagulating atrial fibrillation patients: is there a kidney-friendly choice?

“…Light microscopic finding was characterized by severe glomerular hemorrhage, red blood cells (RBCs) in the Bowman space and formation of compact RBC casts in the tubular lumen. Of note, coexisting glomerular or tubulointerstitial abnormalities, and positive immunofluorescence staining were present in the majority of specimens (17,18). Co-occurrence of WRN with diverse glomerular diseases, including lupus nephritis, IgA nephropathy, and thin basement membrane disease were also described in case reports.…”

The use of anticoagulants in chronic kidney disease: Common point of view of cardiologists and nephrologists

“…The final diagnosis of ARN can be confirmed after a kidney biopsy is performed. The pathogenesis includes glomerular hemorrhage, predominant lesion of tubular epithelial cell injury and obstruction with red blood cells (RBCs) and RBC casts [29]. Notwithstanding, studies, that have examined the incidence of ARN, have relied upon a presumptive diagnosis of ARN defined as GFR changes from baseline over time according to the level of INR control rather than a histopathological diagnosis [27].…”