Lower doses needed as renal function declines.

Renal function plays a role in warfarin response, according to a study conducted at the University of Alabama in Birmingham.

The study found that patients with kidney impairment required lower doses of warfarin and may need closer monitoring to maintain anticoagulation, researchers reported in the Journal of the American Society of Nephrology (2009;20:912-921).

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Nita A. Limdi, PharmD, PhD, and colleagues looked at data on 565 participants in the ongoing Pharmacogenetic Optimization of Anticoagulation Therapy (POAT) study. Patients were divided into three categories of chronic kidney disease (CKD) based on their estimated glomerular filtration rate: no or mild impairment (60 mL/min per 1.73 m­2 or higher); moderate CKD (30 to 59); or severe CKD (30 or less). Most patients (59.5%) had no or mild CKD; 31.2% had moderately impaired function; and 9.4% had 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 compared with patients with no or mild CKD. “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 authors concluded.

Patients in renal failure face a risk for major hemorrhage more than double that of patients with lesser degrees of renal dysfunction. The study did not document or evaluate thromboembolic events. “Kidney function may be important in determining dose for patients with moderate and severe CKD,” Dr. Limdi told Renal & Urology News.

“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.”