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AMPHOTERICIN B- AND FOLIC ACID-INDUCED NEPHROPATHIES IN DEVELOPING RATS
Citation:
Kavlock, R., B. Rehnberg, AND E. Rogers. AMPHOTERICIN B- AND FOLIC ACID-INDUCED NEPHROPATHIES IN DEVELOPING RATS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-85/323 (NTIS PB86162427), 1985.
Description:
The kidneys of newborn rats, which are both morphologically and physiologically immature, have been shown to be relatively insensitive to the nephrotoxic effects of several chemicals. To examine the specificity of these age-related differences, pups received either 20 mg/kg of Amphotericin B or 250 mg/kg folic acid, two known nephrotoxins in adult animals, on either postnatal day 1, 8 or 15. Renal function was examined by a basal clearance test and a hydropenia challenge at 1,2 or 5 (6 in the case of Amphotericin B) days after treatment. The authors observed no difference in degree of renal toxicity with age, but repair of renal damage tended to proceed slower at the youngest age. Amphotericin treatment produced uremia, increased fractional excretion of water and sodium, a decreased fractional excretion of urea, and a diminished hydropenia response but no change in creatinine clearance and no renal pathology. The observed pattern of renal toxicity may be attributed to an inability to maintain urea gradients in the distal segment of the nephron.