Abstract
Renal toxicity and recovery in rats attributed to KW-1070, a new aminoglycoside, were investigated functionally and morphologically in comparison with amikacin and gentamicin.
The rats were divided into low dose groups, given 80mg/kg/day of KW-1070 and amikacin, and 24 mg/kg/day of gentamicin; medium dose groups given 160 mg/kg/day of KW-1070 and amikacin, and 48mg/kg/day of gentamicin; and high dose groups given 320 mg/kg/day of KW-1070 and amikacin, and 96 mg/kg/day of gentamicin.
The results were as follows:
1) Among general conditions, inhibited body weight increase, decreased body weight, increased water intake and decreased food intake were observed. However, these changes were the smallest for KW-1070. No deaths occurred in any of the KW-1070 dose groups, whereas there were deaths in the amikacin and gentamicin high dose groups.
2) In the renal function test, changes attributed to the administration of each drug were observed. Urinary volume, urinary proteins, urinary lysozyme and appearance of occult blood increased, while urinary osmolality decreased. But again, the changes were the smallest for KW-1070. Although decreased total serum protein and increased BUN and serum creatinine were found in the amikacin and gentamicin dose groups, none of these changes were detected in the KW-1070 dose groups.
3) As to drug concentrations in the serum, there were no significant difierences among the three drugs. In concentrations in the kidney, KW-1070 showed lower concentrations than amikacin. After drug administration was stopped, KW-1070 disappeared from the kidney faster than did amikacin and gentamicin.
4) There were dose-related increases in absolute and relative kidney weights in all dose groups, but these changes were smallest in the KW-1070 dose groups.
5) In histopathological examinations, there were dose-related changes, mainly degeneration and necrosis, in the renal tubular epithelium in all dose groups. But the degree of disorder was the mildest in the KW-1070 groups.
As indicated above, the renal toxicity of KW-1070 was clearly milder than that of other aminoglycoside antibiotics.
