Nephrotoxic potential of antiinfective drugs as assessed by tissue-specific proteinuria of renal antigens.
In order to assess the nephrotoxic potential of antibiotics, various aminoglycosides and cephalosporins were tested for their potency to alter the excretion of tubular marker proteins (and brush border antigens) or to change the normal pattern of serumproteinuria as analyzed by SDS polyacrylamidgel gradient electrophoresis. After aminoglycosides, especially after gentamicin injection, a cumulative highly significant increase in the urinary output of marker proteins emerged (healthy volunteer model). In contrast, cephalosporins exhibited practically no nephrotoxic effect on proximal tubule cells. Excretion of tubular marker proteins was enhanced under combined administration of cephalosporins and aminoglycosides mainly due to the aminoglycoside component. There was no nephrotoxic synergy of both drugs. Image analysis of rat kidney sections after injection of aminoglycosides revealed that increased shedding of tubular membrane components under the toxic challenge is followed by rapid inductive repair processes (overshoot protein synthesis) of tubular cells. After a limited acute toxic damage tubular cells may recover within one week.
Scherberich
J E
JE
II. Medical Department, Nephrology, Krankenhaus München-Harlaching of the Ludwig Maximilians University, Germany.
Mondorf
W A
WA
D000293:Adolescent; D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000633:toxicity; D000936:Antigen-Antibody Complex; D015415:Biomarkers / Q000652:urine; D018826:CD13 Antigens / Q000652:urine; D002511:Cephalosporins / Q000008:administration & dosage / Q000009:adverse effects* / Q000633:toxicity; D004347:Drug Interactions; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000633:toxicity; D006801:Humans; D005779:Immunodiffusion; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000097:blood / Q000139:chemically induced* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D000936:Antigen-Antibody Complex; D015415:Biomarkers; D002511:Cephalosporins; D005839:Gentamicins; D018826:CD13 Antigens