Warfarin therapy that results in an International Normalization Ratio above the therapeutic range is associated with accelerated progression of chronic kidney disease

Abstract

Background/aims: We had previously reported that acute kidney injury (AKI) in warfarin-treated chronic kidney disease (CKD) patients may occur shortly after an acute increase in the International Normalization Ratio (INR) >3.0 with formation of occlusive red blood casts. Recovery from this warfarin-associated AKI is poor. Here we investigated whether excessive warfarin therapy could accelerate the progression of CKD.

Methods: We analyzed serum creatinine (SC) and INR in 103 consecutive CKD patients on warfarin therapy in our Nephrology program from 2005 to the present.

Results: Forty-nine patients experienced at least 1 episode of INR >3.0. Of these, 18 patients (37%, Group 1) developed an unexplained increase in SC > or =0.3 mg/dl coincident with INR >3.0 (mean SC increase 0.61 +/- 0.44 mg/dl); 31 patients (63%, Group 2) showed stable SC (mean SC change 0.04 +/- 0.19 mg/dl). Subsequent CKD progression was accelerated in Group 1, but not in Group 2. The 2 groups were not different with respect to demographics, comorbidities, blood pressure, or therapies. However, African Americans were overrepresented in Group 1 (p = 0.035).

Conclusions: Overanticoagulation is associated with faster progression of CKD in a high percentage of patients. Our results indicate the need for prospective trials. Nevertheless, we suggest that our findings are sufficiently compelling at this point to justify extra caution in warfarin-treated CKD patients to avoid overanticoagulation.

Fig. 1

Changes in the SC levels associated with an INR increase >3.0 IU in patients with and without accompanied AKI. Changes in the SC levels (ΔSC) associated with INR increase in patients with accompanied AKI (•, n = 18) and without AKI (▪, n = 31). The mean SC and SD are shown. * p < 0.05, compared to the patients without AKI. Conversion factor for SC in mg/dl to mol/l, ×88.4.

Fig. 2

Changes in SC levels associated with multiple increases in INR >3.0 IU. Changes in SC and INR plotted for 1 patient with multiple episodes of INR >3.0 IU. Elevations in the SC levels were synchronous with abnormally high INR. There were no other associated conditions that could explain the increase in SC. Conversion factor for SC in mg/dl to mol/l, ×88.4.