Renal Handling of Aminoglycosides

Gentamicin nephrotoxicity is attenuated by treatment with other aminoglycosides or with organic poly cations such as spermine, poly aspartate, and polylysine. Initially, competition for binding and intracellular uptake was the postulated mechanism of interaction between gentamicin and polycations. However, recent studies indicate that intracortical concentrations of gentamicin are not reduced in the pres- 

Aminoglycoside binding to membrane acidic phospholipids Changes in content and metabolism of membrane phospholipids Displacement of calcium bound to phospholipids Formation of myeloid bodies 

Alterations in organic acid and base transport Renal wasting of potassium, magnesium, and calcium Polyuria 

Increased state 4, decreased state 3 respiration Decreased DNP-uncoupled respiration 

Alterations in magnesium-controlled, monovalent cation permeability pathway Inhibition of calcium transport Formation of hydrogen peroxide 

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Nagai J, Takano M. Molecular aspects of renal handling of aminoglycosides and strategies for preventing the nephrotoxicity. Drug Metab Pharmacokinet. 2004 19 159-170. 

Nagai J, Tanaka H, Nakanishi N, MurakamlT,Takano M, Role of megalin in renal handling of aminoglycosides. Am J Physiol, 2001 281 F337-44. 

Murphy SW, Barrett BJ, Parfrey PS (2000) Contrast nephropathy. J Am Soc Nephrol 11 177-182 Nagai J, Takano M (2004) Molecular aspects of renal handling of aminoglycosides and strategies for preventing the nephrotoxicity. Drag Metab Phaimacokinet 19 159-170 Nash K, Hafeez A, Hou S (2002) Hospital-acquired renal insufficiency. Am J Kidney Dis 39 930-936... 

The impact of knowledge of renal handling on drugs and xenobiotics on their clinical use is clearly demonstrated with the aminoglycosides (chapter 12). 

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