Phospholipidosis aminoglycosides

Laurent G, Kishore BK, Tulkens PM. Aminoglycoside-induced renal phospholipidosis and nephrotoxicity. Biochem Pharmacol 1990 40 2383. 

Another class of catamphiphilic drugs with high toxic potential is the aminoglycosides. Their nephrotoxicity is manifested by lethal injury to the proximal tubular cells by means of the induction of renal cortical lysosomal phospholipidosis. The toxic effect involves three steps the uptake of the antibiotics into the cells, the intralysoso-mal lipid storage, and, finally, cell necrosis. The aminoglycosides are highly water... 

Aleo MD, Navetta KA, Emeigh Hart SG et al. (2002) Mechanism-based urinary biomarkers of aminoglycoside-induced phospholipidosis. Comp Clin Pathol 11 193-194 de Mendoza SG, Kashyap ML, Chen CY, Lutmer RF (1976) High density lipoproteinuria in nephrotic syndrome. Metabolism 25 1143-1149... 

Aleo MD, Navetta KA, Emeigh Hart SG et al. (2002) Mechanism-based urinary biomarkers of aminoglycoside-induced phospholipidosis. Comp Clin Pathol 11 193-194 Aleo MD, Navetta KA, Emeigh Hart SG et al. (2003) Mechanism-based urinary biomarkers of renal phospholipidosis and injury. Toxicol Sci 72 (Suppl) 243 Bandara LR, Kennedy S (2002) Toxicoproteomics - a new pre-clinical tool. Drug Disc Today 7 411—418 Chapman K (2002) The ProteinChip biomarker system from Ci-phergen Biosystems a novel proteomics platform for rapid biomarker discovery and validation. Biochem Soci Trans 30 82-87... 

After administration of the recommended doses of amikacin for 10 days, renal damage probably occurs in less than 10% of cases. Limited data support the view that amikacin is less nephrotoxic than other aminoglycosides, possibly because of lower binding affinity to proximal tubular cells or reduced potential to cause phospholipidosis (SEDA-20,236). In several prospective randomized studies the liability of amikacin to cause nephrotoxicity was no greater than that of gentamicin or tobramycin (6-8). In a prospective study there was significantly lower nephrotoxicity with amikacin 15 mg/kg/day (4% toxicity) compared with netilmicin 7 mg/kg/day (12%) (9). As with other aminoglycosides, renal toxicity is reversible in most cases (10). 

Laurent G, Carlier MB, Rollman B,Van Hoof F,Tulkens P, Mechanism of aminoglycoside-induced lysosomal phospholipidosis in vitro and in vivo studies with gentamicin and amikacin, Biochem Pharmac, 1982,31(23) 3861-70. 

Feldman S, Wang MY Kaloyanides GJ. Aminoglycosides induce a phospholipidosis in the renal cortex of the rat an early manifestation of nephrotoxicity. J Pharmacol Exp Ther 1982 220 514-520. 

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