Gentamicin-induced acute renal failure in the rat. Effect of dehydration, DOCA-saline and furosemide.
Acute renal failure was induced in rats by subcutaneous injection of 200 mg/kg body weight gentamicin on 3 consecutive days. Following the last gentamicin injection, the animals began to produce increased amounts of dilute urine and usually remained polyuric throughout the experimental period which lasted up to 2 weeks. Plasma concentrations of creatinine rose to values between 2 and 10 mg%, of urea to values between 100 and 1,000 mg% 5-7 days after the last gentamicin injection and returned to levels slightly above control after 14 days. Average proximal tubular pressure was slightly elevated to 13.7 +/- 0.5 mm Hg on the 2nd day after the last gentamicin dose, decreased to 6.1 +/- 0.4 mm Hg after 1 week, and returned to 11.8 +/- 0.2 mm Hg after 2 weeks (control proximal tubular pressure 11.6 +/- 0.2 mm Hg). These average values hide the fact that early in this model of gentamicin-induced acute renal failure many tubules had proximal tubular pressures increased to values between 18 and 25 mm Hg, suggesting tubular obstruction. Decreased proximal tubular pressures and the histological finding of wide-spread necrosis of proximal convolutions is suggestive of tubular leakage. Dehydration, similarly to other models of acute renal failure, markedly potentiated gentamicin-induced acute renal failure. Salt diuresis induced either by DOCA-saline or by furosemide failed to afford functional protection and increased the degree of morphological damage. No relation was found between the concentration of gentamicin in renal tissue and the degree of functional or morphological impairment.
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000617:Aminoglycosides; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003681:Dehydration; D003900:Desoxycorticosterone / Q000494:pharmacology*; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D005839:Gentamicins; D007668:Kidney / Q000473:pathology; D009994:Osmolar Concentration; D011188:Potassium / Q000097:blood; D051381:Rats; D014868:Water Deprivation / Q000502:physiology
D000617:Aminoglycosides; D005839:Gentamicins; D003900:Desoxycorticosterone; D005665:Furosemide; D003404:Creatinine; D011188:Potassium