Urinary Phospholipids Patterns After Treatment With Aminoglycoside Antibiotics and Cis-Platinum

Oto- and nephro-toxicity are the two main limiting factors in the clinical use of aminoglycoside antibiotics. The earliest renal alteration induced by aminoglycosides is the development of a phospholipidosis in proximal tubular cells related to the inhibition of the activities of lysosomal phospholipases and sphingomyelinase (see Tulkens, 1986 for review). Josepovitz et al. (1986) reported that large doses of aminoglycosides, the use of which is associated with the rapid onset of widespread tubular necrosis and kidney dysfunction, induce a marked urinary excretion of phospholipids in rats. We have observed that this excretion already occurs in animals treated at low, clinically relevant doses (Ibrahim & Tulkens, 1986), suggesting that it was not solely due to tubular necrosis and shedding of phospholipid-overloaded cell casts in the lumen. We have therefore examined the phospholipid excretion in humans treated with normal doses of an aminoglycoside, in the absence of significant alteration of the renal function. In parallels we have examined the phospholipid excretion in rats treated with another nephrotoxin acting on proximal tubular cells but which does not cause phospholipidosis, namely cis-platinum.