Nephrotoxicity pp 225-231 | Cite as

Morphological and Functional Impairment of the Developing Rat Kidney Exposed to Gentamicin in Utero

  • Thierri Gilbert
  • Martine Lelievre-Pegorier
  • Bernadette Nabarra
  • Claudie Merlet-Benichou


Aminoglycoside antibiotics used to treat severe bacterial infection during pregnancy can cross the placenta. The effects of in utero exposure to these compounds is receiving increasing attention. It was shown that in the foetal animal, as in the adult, the kidney was the major site of gentamicin accumulation (1). In foetal guinea-pigs whose mothers were given daily 4 mg/kg of gentamicin for the seven days immediately following the period of nephrogenesis, intrarenal gentamicin concentration was found to be about 2 ug/g of tissue. More than two weeks after the treatment to the mother has ceased, the antibiotic released from all maternal and foetal tissues continued to accumulate in the developing kidney, especially as the renal blood flow and glomerular filtration rate increased with age (2). In pups born of gentamicin-treated mothers, impairments of the growth and the function of the proximal tubules were observed, but the damage was transitory (2).


Proximal Tubule Proximal Tubular Cell Glomerular Sclerosis Glomerular Volume Nephron Mass 
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  1. 1.
    M. Lelievre-Pegorier, R. Sakly, A. Meulemans and C. Merlet-Benichou, Kinetics of gentamicin in plasma of non-pregnant, pregnant, and foetal guinea-pigs and itS distribution in foetal tissues, Antimicrob. Agents Chemother. 28:565 (1985).PubMedCrossRefGoogle Scholar
  2. 2.
    M. Lelievre-Pegorier, T. Gilbert, R. Sakly, A. Meulemans, and C. Merlet-Benichou, Effects of foetal exposure to gentamicin on the kidneys of young guinea-pigs, Antimicrob. Agents Chemother. 31: 88 (1987).PubMedCrossRefGoogle Scholar
  3. 3.
    J.P. Mallie, H. Gerard and A. Gerard, Gentamicin administration to pregnant rats. Effect on renal development in utero, Dev. Pharmacol. Ther. 7: 89 (1984).PubMedGoogle Scholar
  4. 4.
    T. Gilbert, M. Lelievre-Pegorier, R. Malienou and C. Merlet-Benichou, Effects of prenatal and postnatal exposure to gentamicin on renal differentiation in the rat, Toxicol. 43:301 (1987).CrossRefGoogle Scholar
  5. 5.
    L. Larsson, Effects of different fixatives on the ultrastructure of the developing proximal tubule in the rat kidney, J. Ultrastruct. Res. 51: 140 (1975).PubMedCrossRefGoogle Scholar
  6. 6.
    H. Movat, Silver impregnation methods for electron microscopy, Am. J. Clin. Pathol. 35:328 (1961).Google Scholar
  7. 7.
    P.S. Chen, T.Y. Toribara and H. Warner, Microdetermination of phosphorus, Anal. Chem. 28:1756 (1964).CrossRefGoogle Scholar
  8. 8.
    J.A. Ramsay and R.H.J. Brown, Simplified apparatus and procedures for freezing-point determination upon small volumes of fluid, J. Sci. Instrum. 32:372 (1955).CrossRefGoogle Scholar
  9. 9.
    R.V. Damadian, E. Shawayri and N.S. Bricker, On the existence of nonurine-forming nephrons in the diseased kidney of the dog, J. Lab. Clin. Med. 65:26 (1965).PubMedGoogle Scholar
  10. 10.
    C. De Rouffignac, S. Deiss and J.P. Bonvalet, Determination du taux individuel de filtration glomerulaire des nephrons accessibles et inaccessibles h la microponction, Pflugers Arch. 315:273 (1970).PubMedCrossRefGoogle Scholar
  11. 11.
    C. Merlet-Benichou, M. Pegorier, M. Muffat-Joly and C. Augeron, Functional and morphologic patterns of renal maturation in the developing guinea-pig, Am. J. Phvsiol. 241:F618 (1981).Google Scholar
  12. 12.
    J.C. Kosek, R. I. Mazze and M.J. Cousins, Nephrotoxicity of gentamicin, Lab. Invest. 30:48 (1974).PubMedGoogle Scholar
  13. 13.
    F.C. Luft, V. Patel, M.N. Yum, B. Patel and S.A. Kleit, Experimental aminoglycoside nephrotoxicity, J. Lab. Clin. Med. 86:213 (1975).PubMedGoogle Scholar
  14. 14.
    D.C. Houghton, M. Hartnett, M. Campbell-Boswell, G. Porter and W. Bennett, A light and electron microscopic analysis of gentamicin nephrotoxicity in rats, Am. J. Pathol. 82:589 (1976).PubMedGoogle Scholar
  15. 15.
    R.H. Cowan, A.F. Jukkola and B.S. Arant, Pathophysiologic evidence of gentamicin nephrotoxicity in neonatal puppies, Pediatr. Res. 14:1204 (1980).PubMedCrossRefGoogle Scholar
  16. 16.
    G. Aubert-Tulkens, F. Van Hoof and P.M. Tulkens, Gentamicin induced lysosomal phospholipidosis in cultured rat fibroblasts, Lab. Invest. 40: 481 (1979).PubMedGoogle Scholar
  17. 17.
    L. Larsson and A.B. Maunsbach, Differentiation of the vacuolar apparatus in cells of the developing proximal tubule in the rat kidney, J. Ultrastruct. Res. 53:254 (1975).PubMedCrossRefGoogle Scholar
  18. 18.
    J. Schaeverbeke and M. Cheignon, Differentiation of glomerular filter and tubular reabsorption apparatus during foetal development of the rat kidney, J. Embryol. Exp. Morph. 58: 157 (1980).PubMedGoogle Scholar
  19. 19.
    P.D. Williams, P. D. Holohan and C.R. Ross, Gentamicin nephrotoxicity. I. Acute biochemical correlates in rats, Am. J. Pathol. 61:234 (1981).Google Scholar
  20. 20.
    T. Gilbert, B. Nabarra and C. Merlet-Benichou, Light and electron microscopic analysis of the kidney in newborn rats exposed to gentamicin in utero, Am. J. Pathol. in press (1987).Google Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Thierri Gilbert
    • 1
  • Martine Lelievre-Pegorier
    • 1
  • Bernadette Nabarra
    • 2
  • Claudie Merlet-Benichou
    • 1
  1. 1.INSERM U13Hopital Claude BernardParis CEDEX 19France
  2. 2.INSERM U25 and CNRS LA122Hopital Necker-Enfants MaladesParisFrance

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