Increased INR>3.0 In Patients on Warfarin Therapy Is Associated with Acute Changes In the Serum Creatinine and Increased Mortality Rate

Abstract

819 Recently we reported that an excessive anticoagulation with warfarin (INR>3.0) can result in acute kidney injury (AKI). Morphologic findings included glomerular hemorrhage and renal tubular obstruction by red blood cell (RBC) casts. The clinical outcome in these patients was unfavorable; more than half of them did not recover from acute kidney injury even after normalization of INR. Later we analyzed serum creatinine (SC) and INR in patients with chronic kidney disease (CKD) on warfarin therapy. We found that 46% of patients had increase in SC levels >0.3 mg/dl associated with INR>3.0. SC remained elevated above baseline after the first episode of abnormal INR. The slope of the following SC increase was higher after this abnormal INR episode. We called this condition warfarin related nephropathy (WRN). The current study is based on medical records of 4059 consecutive patients who were on warfarin therapy at the Ohio State Medical Center for a 5-year period. Of these, 838 (21%) experienced an increase in SC>0.3 mg/dl within 1 week after INR>3.0 (WRN group). The remaining 3221 patients (79%) were designated no-WRN. The WRN group had a 5-year mortality rate of 42%, as compared to 27% for the no-WRN group (p<.001). The highest risk of death in the WRN cohort occurred within the 1st month after INR>3.0 (hazard ratio =2.15). For both WRN and no-WRN groups, the 5-year mortality rate was consistently higher in those with CKD compared to those with no-CKD (50.8% vs. 37.0% for the WRN cohort; 39.7% vs. 24.5% for the no-WRN cohort; p<.0001). Compared to no-WRN patients, WRN patients tended to be older (63.7±14.7 years vs. 61.7±15.6 years, p=.025), diabetic (47% vs 37%, p<.0001), hypertensive (82% vs 72%, p<.001) and had a history of heart failure (62% vs 42%, p<.001). Preliminary models indicate that WRN still is a significant predictor of death even after adjusting for these factors. We conclude that WRN is associated with increased mortality rate in the elderly, the diabetic, and those with CKD and cardiovascular diseases. The possible pathophysiologic mechanisms may be glomerular hematuria and formation of occlusive RBC casts. Physicians, involved in the clinical care of patients on systemic anticoagulation therapy, should be aware of this serious renal complication of warfarin overdose and carefully monitor the kidney function and coagulation parameters in these patients Disclosures: No relevant conflicts of interest to declare.

An Inconspicuous Offender: Apixaban-Induced Anticoagulant-Related Nephropathy

“…The development of casts from red blood cells creates obstruction, further damaging the nephrons, and continued lysis of red blood cells leads to the accumulation of heme-containing molecules and catalytic iron, which creates detrimental hydroxyl radicals [10]. Common risk factors associated with ARN development include overdosing on anticoagulation, concomitant use of interacting medications, CKD, advanced age, diabetes, hypertension, and heart failure [12][13][14]. The incidence of ARN with CKD has been speculated to be as high as 33% in patients receiving warfarin therapy, but the incidence with DOAC therapy is also unknown [15].…”