Changes in serum urea and creatinine during long-term therapy with amiodarone

Abstract

Amiodarone, an antiarrhythmic agent, is hepatically metabolized and with negligible amounts detectable in urine. High dose i.p. administration to rats reduces renal blood flow and creatinine clearance without apparent damage on electron microscopy. In patients, serum creatinine is seen to increase after starting amiodarone therapy. To document the natural history of renal function during long-term therapy in patients receiving amiodarone, we closely followed a cohort of 65 patients for 30 months. Data were analyzed by ANOVA for repeated measures. Mean serum amiodarone, desethylamiodarone (DEA) and urea are displayed on the left axis of the adjacent figure and creatinine on the right axis. A slow increase in serum creatinine reaching a maximum of 11% above baseline at 6 months (p<0.001) was paralleled by an increase in urea to 18% above baseline at 12 months (p<0.001). Uric acid also declined during this time. No further changes were seen beyond the first year of therapy. Conclusions Amiodarone has a clear effect on serum creatinine. Maximum change in parameters of renal function occurs in conjunction with the time that serum concentrations of DEA stabilize during the first year of therapy. The mechanism of effect is unclear, but may involve altered tubular secretion of creatinine or the balance of afferent and efferent renal blood flow. Clinical Pharmacology & Therapeutics (2004) 75, P5–P5; doi: 10.1016/j.clpt.2003.11.019 Figure 1. Download figure to PowerPoint