Mild ischemia predisposes the S3 segment to gentamicin toxicity

David M. Spiegel, Paul F. Shanley, Bruce A. Molitoris

Research output: Contribution to journalArticle

19 Scopus citations


The purpose of these studies was to determine if a functionally insignificant ischemic insult, occurring prior to gentamicin administration, enhanced gentamicin nephrotoxicity. Bilateral renal pedical clamp studies demonstrated that 15 minutes of ischemia did not increase the plasma creatinine yet markedly enhanced gentamicin nephrotoxicity. Further studies, in uninephrectomized rats, demonstrated that following fifteen minutes of renal ischemia and four hours of reperfusion inulin clearance, FENa+ and cellular morphology were normal. This model, therefore was used in all subsequent studies. While the plasma creatinine concentrations were normal 24 hours following 15 minutes of ischemia and only slightly increased following gentamicin administration (100 ms/kg, i.p.) gentamicin administered four hours following 15 minutes of renal ischemia resulted in significantly increased 24-hour plasma creatinine values. Light microscopic quantitation of tissue injury, performed 24 hours following experimental manipulation, was notable tor S3 segment damage in the ischemia plus gentamicin group. This was not observed in either the ischemia group or the sham operated gentamicin group. Cortical gentamicin levels were elevated in the ischemia plus gentamicin group, despite similar plasma gentamicin half-lives. However the elevation in cortical gentamicin levels was dissociated from the enhanced nephrotoxicity seen following mild ischemic injury. Taken together these data indicate that mild renal ischemia, occurring prior to gentamicin administration, greatly enhanced gentamicin nephrotoxicity with the greatest damage occurring to S3 cells.

Original languageEnglish (US)
Pages (from-to)459-464
Number of pages6
JournalKidney international
Issue number3
StatePublished - Sep 1990
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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