title: New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view.
abstract: Nephrotoxicity is one of the most important side effects and therapeutical limitations of aminoglycoside antibiotics, especially gentamicin. Despite rigorous patient monitoring, nephrotoxicity appears in 10-25% of therapeutic courses. Traditionally, aminoglycoside nephrotoxicity has been considered to result mainly from tubular damage. Both lethal and sub-lethal alterations in tubular cells handicap reabsorption and, in severe cases, may lead to a significant tubular obstruction. However, a reduced glomerular filtration is necessary to explain the symptoms of the disease. Reduced filtration is not solely the result of tubular obstruction and tubular malfunction, resulting in tubuloglomerular feedback activation; renal vasoconstriction and mesangial contraction are also crucial to fully explain aminoglycoside nephrotoxicity. This review critically presents an integrative view on the interactions of tubular, glomerular, and vascular effects of gentamicin, in the context of the most recent information available. Moreover, it discusses therapeutic perspectives for prevention of aminoglycoside nephrotoxicity derived from the pathophysiological knowledge.
authors.affiliation: Unidad de Fisiopatología Renal y Cardiovascular, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamanca, Spain. jmlnovoa@usal.es
authors.forename: Jose M
authors.initials: JM
authors.lastname: Lopez-Novoa
authors.forename: Yaremi
authors.initials: Y
authors.lastname: Quiros
authors.forename: Laura
authors.initials: L
authors.lastname: Vicente
authors.forename: Ana I
authors.initials: AI
authors.lastname: Morales
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Lopez-Hernandez
mesh_terms: D000617:Aminoglycosides / Q000009:adverse effects* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000494:pharmacology; D005839:Gentamicins / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000187:drug effects; D007684:Kidney Tubules / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D005839:Gentamicins