Chronic tubufointerstitial nephritis and renal insufficiency associated with long-term "subtherapeutic" gentamicin

Donald Houghton, Janet English, William M. Benett

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

To determine whether long-term "subtherapeutic" concentrations of aminoglycoside produce chronic tubulointerstiial nephropathy, Fisher rats were given gentamicin, 20 mg/kg/day, for up to 6 months via Indwelling osmotic Infusion pumps. Studies included renal histology, autoradiographic quantitation of renal cell tritiated thymidine uptake, renal function and renal cortical gentamicin assay. Acute proximal tubular Injury, without tubular necrosis, followed by recovery, occurred during the first month. Subsequently only mild, nonprogressive tubulointerstitial changes and a twofold Increase In tubular cell turnover were observed. Inulin clearance fell more than 80% during the 6 months of treatment compared with 10% in age-matched controls. Serum creatinine and creatinine clearance overestimated glomerular filtration rate during treatment and did not distinguish treated animals from controls. During the month after 6 months of gentamicin, tubular microcystic changes and active tubulointerstitial nephritis developed, with a continued fall in Inulin clearance. In summary, gintamicin, in "subtherapeutic" doses, produces mild chronic tubulointersititial nephritis with dive renal failure. Cessation of treatment Is associated with microcystic and Inflammatory changes, suggesting that the renal response to tubular Injury can be dissociated from the amount of toxin In the renal cortex. Keeping serum aminoglycoside levels below accepted therapeutic range for 6 months did not preclude nephrotoarlchy.

Original languageEnglish (US)
Pages (from-to)694-703
Number of pages10
JournalThe Journal of Laboratory and Clinical Medicine
Volume112
Issue number6
StatePublished - 1988

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Nephritis
Gentamicins
Renal Insufficiency
Inulin
Aminoglycosides
Kidney
Creatinine
Histology
Thymidine
Rats
Assays
Animals
Pumps
Infusion Pumps
Recovery
Interstitial Nephritis
Withholding Treatment
Wounds and Injuries
Serum
Glomerular Filtration Rate

ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

Cite this

Chronic tubufointerstitial nephritis and renal insufficiency associated with long-term "subtherapeutic" gentamicin. / Houghton, Donald; English, Janet; Benett, William M.

In: The Journal of Laboratory and Clinical Medicine, Vol. 112, No. 6, 1988, p. 694-703.

Research output: Contribution to journalArticle

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