Anticoagulation in Severe Renal Dysfunction: Measurement Challenges and Clinical Implications

To the Editor:

We read with interest Masunaga et al.’s article on antithrombotic therapy trends in atrial fibrillation (AF) patients.¹ Their finding that anticoagulation remained unchanged in patients with creatinine clearance (CrCl) <30 mL/min despite increased direct oral anticoagulant (DOAC) use is concerning, as this cohort showed no reduction in adverse events.

As nephrologists, several critical considerations warrant attention. CrCl assessment has inherent limitations.² CrCl is influenced by muscle mass, potentially overestimating glomerular filtration rate (GFR) in elderly patients with reduced muscle mass. In obesity, CrCl calculated using the Cockcroft-Gault equation may overestimate GFR when using actual rather than ideal body weight. Such discrepancies impact DOAC dosing.

Although pivotal DOAC trials excluded patients with severe renal impairment, emerging evidence suggests certain DOACs may be both safe and efficacious in advanced kidney disease. Siontis et al. demonstrated that apixaban was associated with lower bleeding risk compared to warfarin in hemodialysis patients with AF.³

We emphasize that cystatin C-based GFR estimation may provide superior accuracy in patients with reduced muscle mass or fluctuating renal function. Implementation of novel approaches to renal function assessment could enable optimization of anticoagulation therapy in this challenging population.

The persistent underutilization of anticoagulation in patients with CrCl <30 mL/min identified by Masunaga et al. raises important questions about clinical inertia and physician risk perception. We believe that standardized approaches to renal function assessment and evidence-based DOAC dose adjustments in severe renal dysfunction are urgently needed to address the lack of improvement in clinical outcomes identified in this important study.

Disclosure

All the authors declared no competing interests.

• Hiroki Ito, MD, PhD
• Takefumi Mori, MD, PhD
• Division of Nephrology and Endocrinology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan

References

• 1.   Masunaga N, Ishii M, Oka K, Okamoto K, Yoshida Y, Minami K, et al. 10-year trends of antithrombotic therapy status and clinical outcomes in patients with atrial fibrillation and renal dysfunction: The Fushimi AF Registry. Circ J 2025; 89: 174–183.
• 2.   Hirata S, Shibata A, Miyamura S, Kadowaki D. Theory and practice of accurately assessing the renal function of individual patients. Jpn J Nephrol Pharmacother 2016; 5: 3–18.
• 3.   Siontis KC, Zhang X, Eckard A, Bhave N, Schaubel DE, He K, et al. Outcomes associated with apixaban use in patients with end-stage kidney disease and atrial fibrillation in the United States. Circulation 2018; 138: 1519–1529.