Gentamicin nephrotoxicity. II. Definition of conditions necessary to induce acquired insensitivity

W. Clayton Elliott, Donald Houghton, David N. Gilbert, Joan Baines-Hunter, William M. Bennett

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Abstract

Acquired insensitivity to the nephrotoxic effects of gentamicin develops in Fischer 344 rats after 10 to 14 days' treatment after development of histologic acute tubular necrosis in a setting of extensive histologic regeneration. To determine the relative importance of aminoglycoside exposure, necrosis, and regeneration in the induction of insensitivity, we examined the effect on gentamicin toxicity of prior non-aminoglycoside-mediated tubular necrosis, antecedent nonnecrotizing aminoglycoside exposure, and unilateral Nx-induced renal tubular hyperplasia. Pretreatment with potassium dichromate, which causes tubular necrosis in the same part of the renal cortex as gentamicin, reduced gentamicin-mediated elevation of Scr but had little effect on gentamicin-related tubular dysfunction or structural damage. Pretreatment with netilmicin, which does not cause tubular necrosis, increased the sensitivity of the kidney to gentamicin; toxicity occurred earlier and was more severe. Antecedent unilateral Nx had no demonstrable effect on susceptibility to gentamicin-associated dysfunction, but histologic renal tubular epithelial regeneration and recovery from dysfunction occurred earlier. These results suggest that necrosis and/or regeneration is the major prerequisite for development of gentamicin insensitivity and that the onset of insensitivity is temporally related to the appearance of necrosis and regeneration. However, non-aminoglycoside-mediated necrosis and regeneration fail to fully re-create insensitivity, suggesting that exposure to gentamicin is also necessary.

Original languageEnglish (US)
Pages (from-to)513-525
Number of pages13
JournalThe Journal of Laboratory and Clinical Medicine
Volume100
Issue number4
StatePublished - 1982

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Gentamicins
Necrosis
Regeneration
Kidney
Aminoglycosides
Toxicity
Potassium Dichromate
Netilmicin
Inbred F344 Rats
Hyperplasia
Rats
Recovery

ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

Cite this

Gentamicin nephrotoxicity. II. Definition of conditions necessary to induce acquired insensitivity. / Elliott, W. Clayton; Houghton, Donald; Gilbert, David N.; Baines-Hunter, Joan; Bennett, William M.

In: The Journal of Laboratory and Clinical Medicine, Vol. 100, No. 4, 1982, p. 513-525.

Research output: Contribution to journalArticle

Elliott, W. Clayton ; Houghton, Donald ; Gilbert, David N. ; Baines-Hunter, Joan ; Bennett, William M. / Gentamicin nephrotoxicity. II. Definition of conditions necessary to induce acquired insensitivity. In: The Journal of Laboratory and Clinical Medicine. 1982 ; Vol. 100, No. 4. pp. 513-525.
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