Risk of overanticoagulation during acute kidney injury in patients treated with vitamin K antagonists

Abstract

Background: Vitamin K antagonists (VKAs) are still in use for oral anticoagulation, but not all indications allow their replacement by direct oral anticoagulants. Although formal dose reduction is not required in patients with impaired kidney function, case reports indicate that acute kidney injury (AKI) might be associated with derailment of VKA therapy.

Methods: The study retrospectively collected patients from a tertiary nephrology care centre who experienced AKI while being treated with VKA. In these individuals, the international normalized ratio (INR) as a measure of anticoagulant effect during renal failure was compared with a reference time point with stable kidney function.

Results: A total of 100 patients with AKI and ongoing VKA therapy met the inclusion criteria. The majority (76%) of patients had AKI with CKD. Volume depletion (n = 43), septic renal failure (n = 22), decompensated heart failure (n = 18) and toxic renal damage (n = 11) were the most important causes of AKI. The average INR values at the time of AKI were higher than at the reference time point [median 3.17 (range 1.10-13.0) versus 2.24 (1.07-5.17); P < 0.0001]. Fifty-four patients had INR values above the recommended therapeutic range for their indication at the time point of AKI. Bleeding complications occurred in 24 patients during AKI and the VKA dose had to be reduced in 55. Women, patients with low body mass index and patients with diabetes were predisposed to overanticoagulation during AKI.

Conclusions: The effect of AKI on anticoagulation by VKA has not been systematically described. This risk should be considered in patients at high risk for AKI.

Keywords: acute kidney injury; anticoagulant therapy; bleeding; chronic kidney disease; drug interactions.

FIGURE 1

Patient selection for the study.

FIGURE 2

Distribution of INR values at the time point of AKI and at the reference time point.

FIGURE 3

Percentage of patients with INR values below, within or above the respective recommended target range for their indication. The number of patients with INR values above therapeutic range was higher at the time of AKI (54%) than at the reference time point [14%; odds ratio 7.21 (95% confidence interval 3.62–14.35)].

FIGURE 4

Influence of gender on the percentage of patients with INR values below, within or above target range. Overanticoagulation during AKI was more frequent in female than in male patients [odds ratio 4.12 (95% confidence interval 1.76–9.67)].