The XARENO study provides evidence supporting the use of direct oral anticoagulants (DOACs), specifically rivaroxaban, in atrial fibrillation (AF) patients with advanced chronic kidney disease (CKD) for kidney protection in addition to stroke prevention. The prospective observational study compared adverse kidney outcomes in patients with AF and advanced CKD receiving either rivaroxaban or vitamin K antagonists (VKAs).
Background: AF, CKD, and Anticoagulation
Patients with both AF and CKD face a heightened risk of ischemic stroke, yet also an increased bleeding risk. This has historically led to hesitancy in prescribing oral anticoagulation (OAC) for stroke prophylaxis in this population. While DOACs have become a preferred alternative to VKAs in AF patients, those with advanced CKD (estimated creatinine clearance below 25 to 30 ml/min) were often excluded from pivotal clinical trials.
XARENO Study Details and Outcomes
The XARENO study (NCT02663076) included patients with AF and an eGFR between 15 and 49 ml/min/1.73 m2. The results, analyzed using propensity score overlap weighting Cox regression, demonstrated that adverse kidney outcomes (a composite of eGFR decline to < 15 ml/min/1.73 m2, need for chronic kidney replacement therapy, or development of acute kidney injury) were significantly less frequent in the rivaroxaban group (HR, 0.62; 95% CI, 0.43–0.88). Notably, there was a 61% reduction in the need for chronic kidney replacement therapy (HR, 0.39; 95% CI, 0.17–0.89).
The composite net-clinical benefit outcome (stroke or systemic embolism, major bleeding, myocardial infarction, acute coronary syndrome, or cardiovascular death) was similar in both groups.
Potential Mechanisms of Kidney Protection
VKAs may contribute to vascular calcification and injury, potentially worsening renal function in patients with AF and CKD. This is mediated by the matrix γ-carboxyglutamic acid protein (MGP), a vitamin K–dependent protein that protects against vascular calcification. DOACs like rivaroxaban lack this negative impact on MGP and may even exert protective effects against vascular injury and renal functional decline by decreasing vascular inflammation, remodeling, and calcifications through reduced protease-activated receptor (PAR) signaling.
Implications for Clinical Practice
The XARENO data support a proactive approach to using DOACs in patients with AF and advanced CKD, not only for preventing stroke and systemic embolism but also for protecting the kidneys. These findings mark a turning point in the attitude toward DOAC use in this challenging patient population.
