Protective effect of KCl loading in gentamicin nephrotoxicity.
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 KCl. 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Thompson
J R
JR
Veterans Administration Medical Center, Dallas, TX 75216.
Simonsen
R
R
Spindler
M A
MA
Southern
P M
PM
Cronin
R E
RE
D000818:Animals; D005839:Gentamicins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D007687:Kidney Tubules, Proximal / Q000473:pathology; D009336:Necrosis; D011189:Potassium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis
D005839:Gentamicins; D012965:Sodium Chloride; D011189:Potassium Chloride; D000254:Sodium-Potassium-Exchanging ATPase