Kidney function affects warfarin action in patients with CKD

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Research now under way may one day allow clinicians to customize warfarin doses based on each patient's genetic profile (N Engl J Med. 2009;360:753-764).

In the meantime, a secondary analysis suggests kidney function also plays a role in warfarin response. Patients with kidney impairment seem to require lower doses of warfarin and may need closer monitoring to avoid serious bleeding complications (J Am Soc Nephrol. 2009;20:912-921).

Researchers looked at data generated by 565 participants in the ongoing Pharmacogenetic Optimization of Anticoagulation Therapy study. Patients were divided into three categories of chronic kidney disease (CKD) based on their estimated glomerular filtration rate (eGFR): (1) no or mild impairment (eGFR >60 mL/min/1.73 m2); (2) moderate CKD (eGFR 30-59); or (3) severe CKD (eGFR <30). Most of the patients (59.5%) had no or mild CKD; 31.2% were moderately impaired; and 9.4% had progressed to severe CKD.

As kidney function declined, patients required lower warfarin doses. Patients with severe CKD had less control of anticoagulation and were at higher risk of hemorrhage. “These observations suggest that warfarin may need to be initiated at a lower dosage and monitored more closely in patients with moderate or severe CKD compared with the general population,” the study concludes.

Patients in renal failure face a risk for major hemorrhage more than double that of patients with lesser degrees of renal dysfunction. However, the study included no thromboembolic events.

“Kidney function may be important in determining [warfarin] dose for patients with moderate and severe CKD,” investigators say. “For people in severe CKD or renal failure, whether the risk outweighs the benefit of warfarin therapy cannot be answered by our study, since we did not evaluate thromboembolic events. Therefore, we hesitate to recommend the use of kidney function in making treatment decisions for this subgroup.”
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