Nephrotoxicity of beta-lactam antibiotics: mechanisms and strategies for prevention

  title={Nephrotoxicity of beta-lactam antibiotics: mechanisms and strategies for prevention},
  author={Bruce M. Tune},
  journal={Pediatric Nephrology},
  • B. Tune
  • Published 1 December 1997
  • Biology, Medicine
  • Pediatric Nephrology
The nephrotoxic beta-lactam antibiotics cause acute proximal tubular necrosis. Significant renal toxicity, which has been rare with the penicillins and uncommon with the cephalosporins, is a greater risk with the penems. Mechanisms of injury include: (1) transport into the tubular cell, mainly through the antiluminal organic anion secretory carrier; (2) acylation of target proteins, causing respiratory toxicity by inactivation of mitochondrial anionic substrate carriers; and (3) lipid… 

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This chapter is to summarize the knowledge about the toxicity of β-lactam antibiotics and issues associated to their inappropriate use, including rational prescrib- ing, substitution combination and phage therapy which seems promising.

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Renal Transport of Antibiotics and Nephrotoxicity: a 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 thetubular secretion mechanism (cephalosporins, vancomycin), respectively.

The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1.

It is suggested that OAT1 is the major organic anion transporter in the kidney that is responsible for the renal secretion of antibiotics, especially that of beta-lactam antibiotics.

Cytotoxicity of antiviral nucleotides adefovir and cidofovir is induced by the expression of human renal organic anion transporter 1.

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Molecular-targeted approaches to reduce renal accumulation of nephrotoxic drugs

  • J. NagaiM. Takano
  • Biology, Medicine
    Expert opinion on drug metabolism & toxicology
  • 2010
This review focuses on recent approaches toward prevention of renal accumulation of nephrotoxic drugs, especially aminoglycoside antibiotics and radiolabeled somatostatin analogs, based on the molecular mechanisms underlying cellular uptake in the kidney.

The Activity of Proximal Tubule Enzymes in the Urine of Cephalexin-Treated Patients

The results showing that during the entire period of cephalexin application no changes in NAG, as a lysosomal enzyme, were observed, could be taken as a proof that this antibiotic did not lead to severe injuries of epithelial proximal tubule cells at the level of cell organelles.

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The aim of the study was to analyze scientific literature to determine the likelihood and significance of β-lactam antibiotic DDI mediated by organic anion transporters, as well as potential for predicting it.

The antiviral nucleotide analogs cidofovir and adefovir are novel substrates for human and rat renal organic anion transporter 1.

Data indicate that hOAT1 may significantly contribute to the accumulation of cidofovir and adefovir in renal proximal tubules and, thus, play an active role in the mechanism of nephrotoxicity associated with these antiviral therapeutics.



Renal tubular transport and nephrotoxicity of beta lactam antibiotics: structure-activity relationships.

  • B. Tune
  • Biology
    Mineral and electrolyte metabolism
  • 1994
The several effects of cephaloridine on the tubular cell indicate a potential for different mechanisms of attack on different molecular targets of this complex and rapidly growing group of antimicrobials.

Cephalosporin nephrotoxicity. Transport, cytotoxicity and mitochondrial toxicity of cephaloglycin.

  • B. TuneD. Fravert
  • Biology, Medicine
    The Journal of pharmacology and experimental therapeutics
  • 1980
Very early in vivo respiratory toxicity of cephaloglycin and the lack of significant similar toxicity ofcephalexin provide new evidence that the effect on mitochondria may have a pathogenic role in cephalosporin nephrotoxicity.

Cephalosporin and carbacephem nephrotoxicity. Roles of tubular cell uptake and acylating potential.

Effects of nephrotoxic beta-lactam antibiotics on the mitochondrial metabolism of monocarboxylic substrates.

  • B. TuneC. Hsu
  • Biology
    The Journal of pharmacology and experimental therapeutics
  • 1995
It is proposed that cephaloridine's zwitterionic charge may restrict its ability to acylate monocarboxylic and other anionic carriers, resulting in less nephrotoxicity than might otherwise result from its uniquely high intracellular concentrations.

The renal mitochondrial toxicity of cephalosporins: specificity of the effect on anionic substrate uptake.

  • B. TuneC. Hsu
  • Biology, Medicine
    The Journal of pharmacology and experimental therapeutics
  • 1990
Test the hypothesis that reduced substrate uptake and decreased respiration are causally related and cephaloridine has no significant effect on either the uptake of or respiration with succinate in hepatic mitochondria.

Neurotoxicity of β-lactam antibiotics: predisposing factors and pathogenesis

There is now strong evidence that the concentration of beta-lactam in the brain, and not that in the cerebrospinal fluid, is the decisive factor for the risk of neurotoxic reactions.

Preventive effect of betamipron on nephrotoxicity and uptake of carbapenems in rabbit renal cortex.

Results suggest that BP reduces the nephrotoxicity of carbapenems through inhibiting the active transport of carbAPenems in the renal cortex.

Neurotoxicity of beta-lactam antibiotics: predisposing factors and pathogenesis.

There is now strong evidence that the concentration of beta-lactam in the brain, and not that in the cerebrospinal fluid, is the decisive factor for the risk of neurotoxic reactions.

Thienamycin nephrotoxicity. Mitochondrial injury and oxidative effects of imipenem in the rabbit kidney.

Relationship between the transport and toxicity of cephalosporins in the kidney.

  • B. Tune
  • Biology, Medicine
    The Journal of infectious diseases
  • 1975
It was concluded that the nephrotoxicity of cephaloridine is related to its renal cortical transport with high intracellular concentrations of drug and that this relationship between transport and toxicity exists for cefazolin as well, although the toxicity is of a different order of magnitude.