Protective Effect of KCl Loading in Gentamicin Nephrotoxicity

J. R. Thompson, R. Simonsen, M. A. Spindler, P. M. Southern, R. E. Cronin

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Aminoglycoside nephrotoxicity in experimental animals can be reduced by calcium loading, inducing diabetes, and giving thyroid hormone, while a potassium deficient diet enhances aminoglycoside nephrotoxicity. This study investigated whether potassium loading protects against gentamicin nephrotoxicity in the rat. In part I, group GK ate a diet containing 3.5% potassium and drank 0.2 mol/L KCI. Pair-fed rats eating a standard diet, group G, ate a 1 % potassium diet and drank water. After 10 days, each group received gentamicin subcutaneously, 60 mg/kg twice daily for 8 days. The control groups, K and C, received the high or normal potassium diet, respectively. To control for a protective effect from a high solute load, the effect of equimolar NaCl loading was studied in group GNa and Na. At the end of the 8 days of gentamicin, inulin clearance was significantly higher in GK compared with G (0.6 ± 0.1 v 0.3 ± 0.1 mL/min per 100 g body weight [BW], P < 0.05), but group GNa (0.4 ± 0.1 mL/min per 100 g BW) was not different from group G. Morphological studies demonstrated that potassium-loaded rats (group GK) had significantly less proximal tubular necrosis compared with rats on a standard potassium diet, group G. Sodium loading did not protect against cellular necrosis. Part II studied renal function, cortical Na,K-adenosine triphosphatase (ATPase) and gentamicin accumulation after 2 days of gentamicin to determine the early functional and biochemical effects of potassium loading before overt renal functional impairment. Gentamicin accumulation in the renal cortex was significantly reduced by potassium loading (1.6 ± 0.1 v 2.1 ± 0.1 μg/mg protein, P < 0.025), but was not reduced by sodium loading (1.8 ± 0.1 μ/mg protein). Thus, potassium loading diminished functional and histological evidence of gentamicin nephrotoxicity. The data suggest that reduced accumulation of gentamicin by the renal cortex of potassium-loaded animals is associated with and may be the mechanism of protection.

Original languageEnglish (US)
Pages (from-to)583-591
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume15
Issue number6
DOIs
StatePublished - Jan 1 1990

Keywords

  • Gentamicin
  • potassium loading
  • sodium loading

ASJC Scopus subject areas

  • Nephrology

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