Natural history of aminoglycoside nephrotoxicity in the dog

R. E. Cronin, R. E. Bulger, P. Southern, W. L. Henrich

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58 Scopus citations

Abstract

The natural history of aminoglycoside nephrotoxicity is not well described. This study investigated in the dog renal functional and electrolyte abnormalities during and for 20 days following a 10-day course of low-dose gentamicin (7 mg/kg/day), high-dose gentamicin (30 mg/kg/day), and netilmicin (30 mg/kg/day). Renal histology was examined at the end of the study. Renal functional abnormalities occurred only in animals receiving high-dose gentamicin. A fall in maximal urinary osmolality (1579 ± 347 mOsm/kg/H2O to 450 ± 118, p < 0.05) was followed by renal glycosuria and a fall in GFR (66.9 ± 11.9 ml/min to 21.3 ± 8.6, p < 0.05). These three functional indices had recovered by day 30 in the survivors. Plasma potassium fell in animals receiving high-dose gentamicin (3.8 ± 0.02 mEq/L to 3.3 ± 0.4, p < 0.05) and reached the lowest values (2.7 and 2.9 mEq/L) just prior to death in two animals dying in uremia. Netilmicin also caused a significant fall in plasma potassium (4.3 ± 0.1 mEq/L to 3.9 ± 0.1, p < 0.05). Hypocalcemia (10.0 ± 1.3 mg/dl to 7.8 ± 1.4, p < 0.05) but not hypomagnesemia developed following high-dose gentamicin. Peak serum aminoglycoside levels after high-dose gentamicin and netilmicin were comparable, but trough levels rose only in high-dose gentamicin animals and paralleled the fall in GFR. Light microscopy of the kidney 3 weeks after high-dose gentamicin demonstrated no proximal tubular necrosis but extensive focal tubulointerstitial nephritis, especially in the juxtamedullary cortex. Similar but less extensive derangements were noted in animals receiving low-dose gentamicin, despite the absence of functional abnormalities. Minor histological abnormalities were noted in animals receiving netilmicin. To summarize: 1) major renal functional and electrolyte abnormalities developed only following high-dose gentamicin and included impaired urinary concentration, glycosuria, reduced GFR, hypokalemia, and hypocalcemia (except for a fall in plasma potassium, similar doses of netilmicin were not nephrotoxic); (2) tubulointerstitial nephritis, particularly in the juxtamedullary cortex, occurred with low-dose gentamicin as well as high-dose gentamicin and may be a factor in delayed or incomplete recovery from gentamicin nephrotoxicity; (3) in this model, netilmicin at comparable doses was substantially less nephrotoxic than gentamicin; (4) renal potassium wasting may be a heretofore unrecognized consequence of aminoglycoside administration.

Original languageEnglish (US)
Pages (from-to)463-474
Number of pages12
JournalThe Journal of Laboratory and Clinical Medicine
Volume95
Issue number3
StatePublished - Mar 1980

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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