NEPHROTOXIC POTENTIAL OF ANTIINFECTIVE DRUGS AS ASSESSED BY TISSUE-SPECIFIC PROTEINURIA OF RENAL ANTIGENS

In order to assess the nephrotoxic potential of antibiotics, various a minoglycosides and cephalosporins were tested for their potency to alt er the excretion of tubular marker proteins (and brush border antigens ) or to change the normal pattern of serumproteinuria as analyzed by S DS polyacrylamidgel gradient electrophoresis. After aminoglycosides, e specially after gentamicin injection, a cumulative highly significant increase in the urinary output of marker proteins emerged (healthy vol unteer model). In contrast, cephalosporins exhibited practically no ne phrotoxic effect on proximal tubule cells. Excretion of tubular marker proteins was enhanced under combined administration df cephalosporins and aminoglycosides mainly due to the aminoglycoside component. There was no nephrotoxic synergy of both drugs. Image analysis of rat kidne y sections after injection of aminoglycosides revealed that increased shedding of tubular membrane components under the toxic challenge is f ollowed by rapid inductive repair processes (overshoot protein synthes is) of tubular cells. After a limited acute toxic damage tubular cells may recover within one week.