In utero aminoglycosides-induced nephrotoxicity in rat neonates

Pregnant Wistar females were treated with gentamicin (G), netilmicin (N) or amikacin (A) during two periods of pregnancy covering organogenesis and the beginning of nephrogenesis. Deliveries occurred normally. We studied functional effects--influence of sex, litter size, diuresis, creatinine clearance, G-kidney concentration, and kidney morphological alterations--in rat neonates on day 1 of life. After G and N, the creatinine clearance of the neonates was decreased according to the dosage given to the mother. Whatever the aminoglycoside, kidneys presented proximal tubular alterations (close to those observed in adults) at protonic microscopy and, with electron microscopy, some modifications of distal tubules and of mature and immature glomeruli. It is concluded that the developing kidney can be altered after treating pregnant mothers with aminoglycosides. This model of in utero-induced nephrotoxicity is dose-dependent. Mature and/or immature structures could be affected. The toxicity of the investigated antibiotics could be asserted as G greater than or equal to N greater than A.