Amphotericin B- and folic acid-induced nephropathies in developing rats

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 sc injections of either 20 mg/kg of amphotericin B or 250 mg/kg folic acid, two known nephrotoxins in adult animals, on 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. We 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. Folic acid treatment resulted in greatly increased kidney weights with marked pathology, uremia with decreased creatinine clearance, increased fractional excretion of water, and a decreased hydropenia response. Unlike the renal toxicity observed following amphotericin treatment, renal toxicity from folic acid appears to be a nonspecific response to cell injury within the renal tubules. The data indicate that, in general, neonates do not possess a relative insensitivity to nephrotoxins and that renal physiological measurements which can be performed in neonatal rats are useful in evaluating and interpreting alterations in renal function.