Acute Renal Effects of Amphotericin B

Abstract

Administration of the polyene antibiotic, Amphotericin B (AmB) for the treatment of mycotic diseases has been associated with abnormalities of renal function (1). Its chronic administration in man causes a reduction in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) , renal tubular acidosis, natriuresis, and kaliuresis (2). In the dog, acute administration of AmB results in a similar decrease in GFR and E R P F apparently due to active renal arteriolar constriction ( 3 ) . Studies on the toad and turtle bladder indicate that AmB increases the permeability of the membrane to water, urea and electrolytes (4, 5 ) .This study was designed to determine the acute effects of AmB on the renal tubule and on the intrarenal distribution of blood flow. These results confirm the previously demonstrated decrease in E R P F and GFR. I n addition, there was an increase in the fractional excretion of sodium and potassium. Although free water clearance ( C H~O ) was decreased, the free water reabsorption curve ( T C , ,~/ C,,,) was unaffected, suggesting that the effect of AmB is predominantly at the distal tubule beyond the loop of Henle. The decrease in C H~O was probably due to a decreased distal tubular reabsorption of sodium and an increase in membrane permeability to water. Materials and Methods. The experimentswere performed on female mongrel dogs (12-20 kg) during hydropenia or water diuresis.I . Water diuresis. Eleven dogs were included in this study. All food was withdrawn 16-18 hr before the experiment. Water was permitted ad libitum. The animals were anes-1This project was supported in part by US.Public Health Service Training Grant HE 5353. thetized with sodium pentobarbital (30 mg/kg iv). An endotracheal tube was inserted and connected to a mechanical respirator. The femoral vessels were cannulated for blood sampling, fluid administration, and blood pressure recording, A Foley catheter was placed in the urinary bladder; and complete emptying of the bladder was assured by air washout. An oral water load amounting to 57' 0 of the body weight was administered via a gastric tube, and supplemented by an equal amount of 2.5% dextrose in water given intravenously. Water diuresis was sustained by infusing 0.45% saline at 0.5 ml/kg/min. Inulin and p-aminohippurate solution were infused into the femoral vein to permit clearance measurements. After an equilibration period of 45-60 min or when water diuresis was achieved, 2-4 control urine samples were collected at 5-1 5-min intervals. Blood samples were collected at appropriate times. AmB ( 2 mg/kg) was then infused intravenously at a rate of 0.5 mg/min for approximately 30 min. Thereafter, urine was sampled every 10-1 5-min for approximately 1 hr.ZZ. Antidiuresis. There were 5 animals in this group. Thirty-six hr prior to study the animals were deprived of food and water.Sixteen to 18 hr before the experiment, 5 units of pitressin tannate in oil were given intramuscularly. After endotracheal intubation, vessel cannulation and initial blood and urine sam...

Renal Sparing by Amphotericin B Colloidal Dispersion: Clinical Experience in 572 Patients

“…Although amphotericin B-related renal abnormalities are generally reversible, a minority of patients may develop irreversible renal dysfunction [12]. The nephrotoxicity of CAB is believed to result from a combination of vascular and direct tubular effects [13][14][15]. Infusion of CAB can produce an acute decrease in renal blood flow and glomerular filtration rate.…”

Nephrotoxic Mechanisms of Drugs and Environmental Toxins

“…In particular, rats given repeated injections of amphotericin B developed polyuria, hypostheruria, distal tubular renal acidosis, and potassium wasting. In a complementary study Jose et al (1971) reported a decrease in free water clearance following amphotericin B which was independent of either altered glomerular filtration rate or distal sodium delivery. The later finding is compatible with amphotericin B inducing increased membrane permeability to water at a distal nephron/ collecting duct site.…”

Recurrent Reversible Acute Renal Failure From Amphotericin

“…Renal complica¬ tions include disturbed urinary dilution and concentra¬ tion,1,2 renal tubular acidosis,3 impaired sodium and potas¬ sium conservation,1,4 and both acute and chronic renal failure. 1,4,5 Although rat6 and canine7 models have demonstrated immediate depression of both whole kidney and single nephron glomerular filtration rate (GFR) after exposure to amphotericin, the onset of impaired renal function in hu¬ mans typically does not develop until several days after the initiation of amphotericin therapy.3,8 Immediate acute renal failure (ARF) following amphotericin administration has not previously been reported in humans. We describe a patient with long-standing cryptogenic cirrhosis of the liver who had recurrent, immediate acute renal failure with each of four attempts to administer amphotericin.…”