cefotaxime and Proteinuria

Nephrotoxicity of cefodizime sodium (THR-221), a new cephem antibiotic, was studied in rats by comparing its toxic effect with those of other cephem antibiotics including cephaloridine (CER), cefazolin (CEZ) and cefmetazol (CMZ). Each drug was administered single and consecutive 14-day dosage with its alone or in combination with either furosemide or gentamicin. The results are summarized as follows: 1. In the single dosage study, the rats treated with THR-221 at dose levels of 1200 mg/kg and more showed slight changes in urinary protein and glucose. In rats treated with CER at a dose of 1200 mg/kg, creatinine level in plasma and weights of kidneys were increased, and degeneration and/or necrosis of the renal proximal tubular epithelia were observed. Furthermore, by the consecutive dosage of CER at a dose of 1000 mg/kg, remarkable renal responses including increase in urinary protein and glucose, and weights of kidneys, were observed. In addition, histopathological examinations showed degeneration and/or regeneration of the renal proximal tubular epithelia. 2. No enhanced effect of nephrotoxicity by combination with furosemide or gentamicin was observed except in case of combination of CER with furosemide. 3. The above results indicate that the nephrotoxic potency among these four antibiotics on the single and consecutive dosage studies is CER much greater than THR-221 greater than or equal to CEZ = CMZ and CER much greater than THR-221 = CEZ = CMZ, in the decreasing order.

Topics: Animals; Cefazolin; Cefmetazole; Cefotaxime; Cephaloridine; Drug Administration Schedule; Drug Therapy, Combination; Epithelium; Furosemide; Gentamicins; Glycosuria; Injections, Intravenous; Kidney; Kidney Tubules; Male; Necrosis; Organ Size; Proteinuria; Rats; Rats, Inbred Strains

Cefotiam (CGP 14221/E; SCE 963), a semisynthetic cephalosporin, was administered as a single dose by i.v. injection to rats l(up to 1.8 g/kg body-weight) and rabbits (up to 1.7 g/kg body-weight). Cephaloridine served as positive control (1.0 and 0.75 g/kg in rats; 0.3 and 0.28 g/kg in rabbits). The animals were sacrificed 24 h after injection and the kidneys preserved for routine histology and enzyme histochemistry (alkaline phosphatase, aminopeptidase, succinate dehydrogenase, esterase). Serum samples (Na+, K+, Cl-, urea, creatinine, LDH, alkaline phosphatase) and 24-h urine (Na+, K+, Cl-, urea, creatinine, protein, LDH, aminopeptidase) were analysed before and 24 h after injection. Minimal, irregularly scattered, degenerative changes in the proximal tubules which were not dose-dependent in degree were observed in rat kidneys following cefotiam injection. A slight dose-dependent degeneration in up to 50% of proximal tubular cells with loss of brush-border membrane enzyme activity was observed in rabbit kidneys. In both animal species the ability to concentrate urine was retained and urea and creatinine serum levels hardly affected. Following cefotiam injection a dose-dependent 4-fold excretion of urinary protein but not of LDH was observed in rabbits only. By contrast, cephaloridine caused extensive degeneration and necrosis in up to 90% of proximal tubular cells in both rats and rabbits, which was accompanied with formation of enzymically active hyaline casts, loss of urine-concentrating capacity of the kidney, elevated serum levels of urea and creatinine and an increased urinary excretion of LDH (60-fold in rats, 20-fold in rabbits) and protein (3-fold in rats, 10-fold in rabbits). Histochemistry and electron microscopy of rabbit kidneys suggested a loss of microvilli from proximal tubule cells by endocytosis and thus degeneration following injection of large doses of cefotiam, whereas cell disruption and necrosis prevailed after cephaloridine. The action of cefotiam on the proximal tubule cells is, therefore, not only quantitatively but possibly also qualitatively different from that of cephaloridine. Semiquantitative evaluation of tubular injuries in alkaline phosphatase-stained kidney sections and measurements of LDH and protein content in 24-h urine samples were advantageous in determining the quantity and the quality of nephrotoxic effects.

Topics: Animals; Cefotaxime; Cefotiam; Cephaloridine; Enzymes; Female; Histocytochemistry; Kidney Diseases; Male; Proteinuria; Rabbits; Rats