Interaction of ischemic and antibiotic-induced injury in the rabbit kidney.

Abstract

The tubular necrosis produced by transient unilateral ischemia, three toxic cephalosporins, and the aminoglycoside neomycin were studied separately and in different combinations in the rabbit kidney. It was found that (1) mildly damaging transient ischemia (25 min) and a minimally toxic dose of the rapidly secreted cephalosporin cephaloglycin (60 mg/kg of body weight) are synergistically damaging; (2) there is no synergy between ischemia and the nonsecreted cephalosporin cephaloridine (90 mg/kg); and (3) ischemia and neomycin (100 mg/kg per day for three days) are not additively damaging, but the aminoglycoside has an additive effect with the combined insults of ischemia and cefazolin (500 mg/kg). Studies of transport showed that ischemia potentiates cephalosporin toxicity probably because it increases postischemic antibiotic concentrations in proximal tubular cells and that this increased uptake is the result of transiently augmented tubular secretion. Although this ischemic protocol reduced inulin clearance by 40%, it increased cephaloglycin secretion by an amount more than sufficient to overcome the decrease in filtration.

• Authors: M C Browning, C Y Hsu, P L Wang, B M Tune
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 147 Issue 2 Pg. 341-51 (Feb 1983) ISSN: 0022-1899 [Print] United States
• PMID: 6827149 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cephalosporins
• Inulin
• Neomycin
• Cephaloglycin

Topics

• Acute Kidney Injury (etiology)
• Animals
• Cephaloglycin (adverse effects, metabolism)
• Cephalosporins (adverse effects)
• Female
• Inulin
• Ischemia (complications, physiopathology)
• Kidney (blood supply)
• Kidney Function Tests
• Kidney Tubular Necrosis, Acute (chemically induced, etiology)
• Neomycin (adverse effects)
• Rabbits