title: Nephrotoxicity of aminoglycoside antibiotics.
abstract: Aminoglycoside antibiotics cause transient, usually nonoliguric, renal failure in up to 10-30% of patients treated with these drugs, and are the cause of the largest proportion of drug-induced acute nephrotoxicities. The toxic mechanism includes (i) uptake of the drug by proximal tubular cells, where it is first sequestered within lysosomes and (ii) development of a lysosomal phospholipidosis, which is rapidly associated with cell necrosis and various alterations to subcellular structure and function. Tubular necrosis is often accompanied by (and probably triggers) tubular regeneration and peritubular proliferation. The means whereby such tubular alterations eventually cause a decline in glomerular filtration and hypo-osmotic polyuria has not been established. Various in-vitro and acellular models have been designed to assess and screen for the nephrotoxic potential of aminoglycosides; of these, methods based on the analysis of aminoglycoside-phospholipid interactions appear to be the most meaningful. A number of patient- and drug-related risk factors have been identified, and their avoidance could significantly reduce the risk of nephrotoxic reactions. Because the uptake of aminoglycosides by the kidney is saturable, administration of daily doses of these drugs as one or two injections, rather than as multiple injections or by continuous infusion, may also decrease the risk for toxicity.
authors.affiliation: Laboratoire de Chimie physiologique, Université Catholique de Louvain, Bruxelles, Belgium.
authors.forename: P M
authors.initials: PM
authors.lastname: Tulkens
mesh_terms: D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000633:toxicity*; D004195:Disease Models, Animal; D006801:Humans; D007676:Kidney Failure, Chronic / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012307:Risk Factors
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents