Chronic amphotericin B nephrotoxicity in the rat, protective effect of prophylactic salt loading

Amphotericin B (AMPHO) is the most effective and widely used antifungal agent for the treatment of systemic fungal disease in man. Its use is frequently limited by the development of nephrotoxicity, including renal vasoconstriction with depressed glomerular filtration rate (GFR) and renal plasma flow (RPF), inability to concentrate the urine, and renal potassium wasting. We investigated the effects of oral NaCl loading during chronic administration of AMPHO, on renal function in the rat. Rats were provided 150 mmol/L NaCl (AMPHO plus NaCl) or tap water (AMPHO plus H2O) as drinking water, 3 days prior to, and during chronic AMPHO (5 mg/kg/d intraperitoneal [IP] for 21 days). At the end of the experimental period, renal functional parameters were determined, including serum creatinine, urinary volume and electrolyte excretion rates, ability to maximally concentrate the urine after water deprivation, and renal hemodynamics. NaCl supplementation prevented the rise in serum creatinine (AMPHO plus NaCl, initial v final, 0.39 +/- 0.03 v 0.40 +/- 0.03 mg/dL [34.6 +/- 2.7 v 35.4 +/- 2.7 mumol/L], P = NS) seen in AMPHO plus H2O (0.34 +/- 0.01 v 0.51 +/- 0.04 mg/dL [30.0 +/- 0.9 v 45.2 +/- 3.5 mumol/L], P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)