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Pediatric Nephrology

, Volume 11, Issue 6, pp 768–772 | Cite as

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

  • Bruce M. Tune
Original article

Abstract

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 peroxidation. The most nephrotoxic beta-lactams available for study are cephaloridine, cephaloglycin, and imipenem; panipenem, which is comparably nephrotoxic, is currently available only in Japan. Cephaloridine has several unique properties, probably all caused by its pyridinium side-group: (1) its secretory transport into the tubular cell is followed by minimal cell to luminal fluid movement, resulting in extreme intracellular sequestration; (2) it is the only beta-lactam shown to cause significant oxidative injury; (3) it has a limited ability to attack the mitochondrial carriers for pyruvate and the short-chain fatty anions. Cephaloglycin and imipenem undergo less intracellular trapping than cephaloridine, but have sufficient tubular cell uptake, reactivity, and generalized toxicity to mitochondrial substrate carriers to be severely nephrotoxic. Cephaloridine and cephaloglycin are no longer used clinically. Imipenem and panipenem are marketed in combination with nephroprotective renal transport inhibitors. Strategies for avoiding renal toxicity with new cephalosporins and penems are discussed.

Key words: Beta-lactam antibiotics Nephrotoxicity Prevention 

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Copyright information

© IPNA - International Pediatric Nephrology Association New York, USA 1997

Authors and Affiliations

  • Bruce M. Tune
    • 1
  1. 1.Laboratory of Renal Pharmacology, Division of Nephrology, Department of Pediatrics – G-306, Stanford University School of Medicine, Stanford, California 94305-5119, USAUSA

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