TY - JOUR
T1 - Protective Effect of KCl Loading in Gentamicin Nephrotoxicity
AU - Thompson, J. R.
AU - Simonsen, R.
AU - Spindler, M. A.
AU - Southern, P. M.
AU - Cronin, R. E.
PY - 1990
Y1 - 1990
N2 - 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.
AB - 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.
KW - Gentamicin
KW - potassium loading
KW - sodium loading
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U2 - 10.1016/S0272-6386(12)80530-0
DO - 10.1016/S0272-6386(12)80530-0
M3 - Article
C2 - 2164323
AN - SCOPUS:0025338443
SN - 0272-6386
VL - 15
SP - 583
EP - 591
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 6
ER -