Renal cortex ion composition and Na-K-ATPase activity in gentamicin nephrotoxicity.
Abnormalities of potassium and magnesium homeostasis have been reported following the use of gentamicin, and potassium depletion enhances gentamicin nephrotoxicity. The present study investigates these relationships in the dog by assessing changes in renal cortex ion composition and renal cortex Na-K-ATPase activity occurring during gentamicin nephrotoxicity. Gentamicin (15 mg/kg i.m. twice daily) was administered for 4 to 7 days to potassium-depleted or potassium-supplemented animals. The results show that gentamicin nephrotoxicity was characterized by a significant reduction in renal cortex content of potassium (17%), magnesium (19%), and phosphorus (12%) in all groups of animals given gentamicin. However, only potassium-depleted animals exposed to 7 days of gentamicin experienced a significant rise in plasma creatinine (from 1.3 +/- 0.1 to 4.3 +/- 1.0 mg/dl). Accompanying this increase in plasma creatinine was a significant rise in the renal cortex content of sodium (from 25 +/- 0.5 to 27.9 +/- 1.7 meq/100 g fat-free dry solid wt) and calcium (from 1.2 +/- 0.1 to 2.6 +/- 0.3 mM/100 g fat-free dry solid wt). Na-K-ATPase activity in the renal cortex fell only in potassium-depleted animals after 4 days (from 11.5 +/- 0.9 to 7.8 +/- 0.1 microM Pi.mg protein-1.h-1) and 7 days (5.9 +/- 0.8 microM Pi.mg protein-1.h-1) of gentamicin treatment. Thus, gentamicin nephrotoxicity is characterized by sequential changes in renal cortex ionic composition, sodium pump activity, and renal function.
D000818:Animals; D003404:Creatinine / Q000097:blood; D004285:Dogs; D004573:Electrolytes / Q000032:analysis* / Q000097:blood; D005839:Gentamicins / Q000097:blood / Q000633:toxicity*; D007477:Ions; D007672:Kidney Cortex / Q000032:analysis / Q000201:enzymology*; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D008903:Minerals / Q000032:analysis*; D011188:Potassium / Q000032:analysis; D012083:Renin / Q000097:blood; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D004573:Electrolytes; D005839:Gentamicins; D007477:Ions; D008903:Minerals; D003404:Creatinine; D012083:Renin; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium