![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
JE Foster, ES Harpur and HO Garland
Pharmaceutical Sciences Institute, Aston University, Birmingham, U.K.
Standard renal clearance techniques were used to investigate the acute effects of gentamicin on renal electrolyte handling in anesthetized rats. Data were obtained before substantial changes in tubular integrity would be expected to occur, thus permitting a distinction between the actions of the drug per se and renal changes resulting from underlying tubular damage. Infusion of gentamicin over a 3-hr period resulted in an immediate and sustained calciuresis and magnesiuresis, with no significant change in the renal clearance of sodium or potassium. Within 60 min of the onset of drug infusion at 0.28 mg/kg/min, renal calcium clearance (ml/min) increased from 0.095 +/- 0.013 to 0.210 +/- 0.016 (P less than .001) and renal magnesium clearance (ml/min) increased from 0.538 +/- 0.059 to 0.662 +/- 0.053 (P less than .01). Because it was subsequently shown that infusion of gentamicin did not alter glomerular filtration rate, it is clear that both responses resulted from a reduced tubular reabsorption of the respective ions; they were rapidly reversible when gentamicin infusion ceased. A higher dose of gentamicin (0.56 mg/kg/min for 3 hr) also significantly decreased plasma magnesium concentrations (0.40 +/- 0.01 vs. 0.49 +/- 0.02 mmol/l, treated vs. control; P less than .01). Gentamicin-induced changes in the renal handling of calcium and magnesium, therefore, occur independently of and before the development of nephrotoxicity. They may be at least partially responsible for the alteration in electrolyte homeostasis seen in humans during aminoglycoside treatment (e.g., hypomagnesemia). It is interesting to speculate on the possibility that they may also in some way contribute to the subsequent cellular injury that is known to occur with prolonged use of gentamicin.
This article has been cited by other articles:
|
|
 |
|
  S. Notenboom, A. C. Wouterse, B. Peters, L. H. Kuik, S. Heemskerk, F. G. M. Russel, and R. Masereeuw Increased Apical Insertion of the Multidrug Resistance Protein 2 (MRP2/ABCC2) in Renal Proximal Tubules following Gentamicin Exposure J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 1194 - 1202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Notenboom, D. S. Miller, L. H. Kuik, P. Smits, F. G. M. Russel, and R. Masereeuw Short-Term Exposure of Renal Proximal Tubules to Gentamicin Increases Long-Term Multidrug Resistance Protein 2 (Abcc2) Transport Function and Reduces Nephrotoxicant Sensitivity J. Pharmacol. Exp. Ther., November 1, 2005; 315(2): 912 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Nagai, H. Tanaka, N. Nakanishi, T. Murakami, and M. Takano Role of megalin in renal handling of aminoglycosides Am J Physiol Renal Physiol, August 1, 2001; 281(2): F337 - F344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-J. Dai, G. Ritchie, D. Kerstan, H. S. Kang, D. E. C. Cole, and G. A. Quamme Magnesium Transport in the Renal Distal Convoluted Tubule Physiol Rev, January 1, 2001; 81(1): 51 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. O. von Vigier, A. C. Truttmann, K. Zindler-Schmocker, A. Bettinelli, C. C. Aebischer, B. Wermuth, and M. G. Bianchetti Aminoglycosides and renal magnesium homeostasis in humans Nephrol. Dial. Transplant., June 1, 2000; 15(6): 822 - 826. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. S. AGUS Hypomagnesemia J. Am. Soc. Nephrol., July 1, 1999; 10(7): 1616 - 1622. [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
