Effect of aminophylline on amphotericin B nephrotoxicity in the dog

The polyene antibiotic, amphotericin B, causes an acute reduction in renal blood flow and glomerular filtration rate. The purpose of this study was to evaluate the hypothesis that the renal vascular response to amphotericin B can be blocked by aminophylline. Toward this end, the effect of aminophylline on the renal response to amphotericin B in sodium-depleted dogs was examined. In dogs not treated with aminophylline, amphotericin B (0.5 mg/kg infused i.v. over 20 min) significantly reduced renal blood flow and glomerular filtration by 49.9 +/- 12.6 ml/min (mean +/- S.E.M.) and 23.4 +/- 2.4 ml/min, respectively at 140 min after the amphotericin B infusion. In dogs treated with an intrarenal aminophylline infusion (5 mg/min), the renal blood flow and glomerular filtration rate response to amphotericin B did not differ from that of amphotericin B vehicle. We conclude that aminophylline inhibits the renal response to amphotericin B. The possible clinical relevance of these observations are discussed.