Author + information
- Yajuan Yang, BS,
- Guangping Li, MD, PhD and
- Tong Liu, MD, PhD∗ ()
- ↵∗Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin, Medical University, 23 Pingjiang Road, Hexi District, Tianjin 300211, People’s Republic of China
We congratulate Bohm et al. (1) for their interesting study regarding the effects of warfarin or dabigatran etexilate (DE) on renal function in the patients with atrial fibrillation (AF) receiving oral anticoagulation, showing a decline in renal function that was greater in those taking warfarin compared with DE, which was amplified by diabetes and previous vitamin K antagonist use. The authors propose this adverse renal outcome may be due to inhibition by warfarin of vitamin K–dependent matrix gamma-carboxyglutamic acid (Gla/MPG) and resulting in renal vascular calcification and arterial damage.
Recent data showed that excessive anticoagulation with warfarin can result in acute kidney injury (AKI) by causing glomerular hemorrhage and renal tubular obstruction by red blood cell (RBC) casts in some patients, especially in those with chronic kidney disease (CKD), which was described as warfarin-related nephropathy (WRN) (2). Brodsky et al. (3) was the first to describe this entity through kidney biopsy in a subset of patients with warfarin overdose, hematuria, and AKI, and each biopsy specimen demonstrated evidence of acute tubular injury, glomerular hemorrhage, and renal tubular obstruction by RBC casts. Actually, oxidative stress damage to tubules by an RBC cast, even though the RBC cast did not obstruct the tubule, could lead to WRN. Other important mechanisms, including atheroembolism, interstitial nephritis, apoptosis of glomerular endothelial cells, and direct effects of warfarin on the glomerulus, may also contribute to the development of WRN.
A recent case report (4) also described an anticoagulant-related AKI in a patient who was receiving the thrombin inhibitor dabigatran. Furthermore, Ryan et al. (5) investigate the effects of dabigatran on kidney function in an animal model of CKD, demonstrating that dabigatran resulted in a dose-dependent increase in serum creatinine and hematuria in both control and 5/6 nephrectomy rats. Morphologically, the findings in 5/6 nephrectomy rats treated with dabigatran were similar to those found in animals with WRN, involving RBC tubular casts and acute tubular injury. Unexpectedly, in comparison with WRN, in which kidney injury was seen only in 5/6 nephrectomy rats, the effects of dabigatran were highlighted in control rats as well. These findings suggest that the risk to the kidney by dabigatran may be greater than that by warfarin in patients with normal renal function, which should be taken into account in clinical practice, indicating that regular monitoring of kidney function may be necessary in patients receiving oral anticoagulation therapy including warfarin or dabigatran.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Böhm M.,
- Ezekowitz M.D.,
- Connolly S.J.,
- et al.
- ↵Kadiyala D, Brewster UC, Moeckel GW. Dabigatran induced acute kidney injury. Paper presented at: The American Society of Nephrology Annual Meeting; November 1–4, 2012; FR-PO1122, San Diego, California.
- Ryan M.,
- Ware K.,
- Qamri Z.,
- et al.