INCREASING DIETARY CALCIUM MODERATES EXPERIMENTAL GENTAMICIN-NEPHROTOXICITY

  • 1 January 1984
    • journal article
    • research article
    • Vol. 103  (1) , 104-114
Abstract
Because Ca2+ may modify gentamicin [an antibiotic] binding to its proximal tubular brush border membrane receptor, the effects of dietary Ca2+ loading and subsequent hypercalciuria on experimental gentamicin nephrotoxicity were studied. Male Fischer 344 rats were fed 1 of 2 diets that were identical except for CaCO3 content: normal (0.5%) and high (4%). The high-Ca2+ diet made rats hypercalciuric, but there were no diferences between the 2 groups in inulin clearance, Na+ or osmolar excretion, or serum Ca2+ prior to gentamicin administration. Animals on both diets were treated with gentamicin, 20 mg/kg b.i.d. [twice/day], for periods of 3-21 days. Both groups developed acute renal failure, but animals on the high-Ca2+ diet had less severe acute toxic injury, as evidenced by studies of inulin clearance, renal histology, and in vitro cortical uptake of NMN [methylnicotinamide] and PAH [p-aminohippurate]. Ca2+-loaded animals tended to have lower peak renal cortical gentamicin levels during the period of acute toxicity. The mechanism by which increased dietary Ca2+ protects against gentamicin nephrotoxicity remains speculative. Ca2+ and gentamicin may compete for the same brush border receptor, or alternatively, parathyroid suppresion may result in diminution in tubular cell membrane drug binding sites. High-Ca2+ diets may exert a nonspecific salutory effect on proximal tubular cell integrity.

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