Aminoglycoside-mediated calciuresis.
Gentamicin and calcium compete for binding to various tissues including renal tubular brush border. Moreover, gentamicin has calcium channel blocking properties in cardiac and vascular tissue. Calcium channel blockade in vitro by nifedipine or verapamil decreases calcium uptake by renal tubular epithelial cells. To determine the acute in vivo effects of gentamicin on renal calcium handling, we administered gentamicin 10 mg/kg as an i.v. bolus to F344 rats. Within 30 min of administration fractional excretion of calcium increased from a mean of 11 +/- 2% (S.E.M.) to 128 +/- 37%. There was no change in glomerular filtration rate, or urinary sodium, potassium or phosphate excretion. Maximum calciuria occurred immediately after administration, was dose-related and was correlated to preadministration urinary calcium. Urine calcium concentration was also correlated to urinary gentamicin concentration. Urinary calcium returned to base-line values within 90 min of bolus gentamicin administration, but remained elevated if a gentamicin infusion was continued. Parathyroidectomy and dietary calcium content did not affect gentamicin calciuria. Tobramycin, a less nephrotoxic aminoglycoside in the F344 rat, had calciuric effects similar to gentamicin. Verapamil, a calcium channel blocker which is largely excluded from the urine, and potassium dichromate, a nonaminoglycoside proximal tubular nephrotoxin, had no effect on urinary calcium. The mechanism of aminoglycoside calciuria is unclear, but may be related to competition between aminoglycosides and calcium for brush border binding, intraluminal calcium channel blockade by aminoglycosides or aminoglycoside inhibition of basolateral calcium ATPase or Na-K ATPase.
Elliott
W C
WC
Department of Medicine, State University of New York, Syracuse.
Patchin
D S
DS
D000818:Animals; D002118:Calcium / Q000652:urine*; D002136:Calcium, Dietary / Q000378:metabolism; D005839:Gentamicins / Q000494:pharmacology*; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016105:Parathyroidectomy; D051381:Rats; D011916:Rats, Inbred F344; D014031:Tobramycin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002136:Calcium, Dietary; D005839:Gentamicins; D014700:Verapamil; D002118:Calcium; D014031:Tobramycin