Renal transport of antibiotics and nephrotoxicity: a review.
The renal excretion of a drug can essentially be divided schematically into three functional processes: glomerular filtration, tubular reabsorption and tubular secretion. When assessing nephrotoxicity, the tubular secretion system, which allows transport of the drug from the blood to the urine via the tubular cells, is particularly important. Historically, two distinct tubular secretion mechanisms have been described for drugs: one via organic cations and the other via organic anions. More recently, a third tubular secretion mechanism has been identified, mediated by P-glycoprotein. In the present review, a number of examples will be given relating to antibiotic-induced kidney damage determined via the tubular reabsorption mechanism (aminoglycosides, amphotericin B) and via the tubular secretion mechanism (cephalosporins, vancomycin), respectively. Drug transport within the tubular cells is the first fundamental stage in the onset of the nephrotoxic process. Knowledge of these concepts is important for the prevention of iatrogenic kidney damage, particularly in patients with underlying disease receiving concomitant treatment with several potentially nephrotoxic molecules.
Fanos
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Clinica Pediatrica, Università degli Studi di Verona, Roma, Italy. vafanos@tin.it
Cataldi
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D000042:Absorption; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000493:pharmacokinetics*; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D007684:Kidney Tubules / Q000187:drug effects / Q000502:physiology*
D000900:Anti-Bacterial Agents