Sodium status influences chronic amphotericin B nephrotoxicity in rats.
The nephrotoxic potential of amphotericin B (5 mg/kg per day intraperitoneally for 3 weeks) has been investigated in salt-depleted, normal-salt, and salt-loaded rats. In salt-depleted rats, amphotericin B decreased creatinine clearance linearly with time, with an 85% reduction by week 3. In contrast, in normal-salt rats creatinine clearance was decreased but to a lesser extent at week 2 and 3, and in salt-loaded rats creatinine clearance did not change for 2 weeks and was decreased by 43% at week 3. All rats in the sodium-depleted group had histopathological evidence of patchy tubular cytoplasmic degeneration in tubules that was not observed in any normal-salt or salt-loaded rat. Concentrations of amphotericin B in plasma were not significantly different among the three groups at any time during the study. However, at the end of 3 weeks, amphotericin B levels in the kidneys and liver were significantly higher in salt-depleted and normal-salt rats than those in salt-loaded rats, with plasma/kidney ratios of 21, 14, and 8 in salt-depleted, normal-salt, and salt-loaded rats, respectively. In conclusion, reductions in creatinine clearance and renal amphotericin B accumulation after chronic amphotericin B administration were enhanced by salt depletion and attenuated by sodium loading in rats.
Ohnishi
A
A
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Ohnishi
T
T
Stevenhead
W
W
Robinson
R D
RD
Glick
A
A
O'Day
D M
DM
Sabra
R
R
Jackson
E K
EK
Branch
R A
RA
D000666:Amphotericin B / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D003404:Creatinine / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D011188:Potassium / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000502:physiology* / Q000652:urine; D013997:Time Factors
D000666:Amphotericin B; D012964:Sodium; D003404:Creatinine; D011188:Potassium