title: Increasing dietary calcium moderates experimental gentamicin nephrotoxicity.
abstract: Because calcium has been reported to modify gentamicin binding to its proximal tubular brush border membrane receptor, we studied the effects of dietary calcium loading and subsequent hypercalciuria on experimental gentamicin nephrotoxicity. Male Fischer 344 rats were fed one of two diets that were identical except for calcium carbonate content: normal (0.5%) and high (4%). The high-calcium diet made rats hypercalciuric but there were no differences between the two groups in inulin clearance, sodium or osmolar excretion, or serum calcium prior to gentamicin administration. Animals on both diets were treated with gentamicin, 20 mg/kg b.i.d., for periods of 3 to 21 days. Both groups developed acute renal failure, but animals on the high-calcium diet had less severe acute toxic injury, as evidenced by studies of inulin clearance, renal histology, and in vitro cortical uptake of NMN and PAH. Furthermore, calcium-loaded animals tended to have lower peak renal cortical gentamicin levels during the period of acute toxicity. The mechanism by which increased dietary calcium protects against gentamicin nephrotoxicity remains speculative. Calcium and gentamicin may compete for the same brush border receptor or alternatively parathyroid suppression may result in diminution in tubular cell membrane drug binding sites. The possibility that high-calcium diets exert a nonspecific salutory effect on proximal tubular cell integrity has not been excluded.
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004032:Diet; D005839:Gentamicins / Q000009:adverse effects*; D007444:Inulin; D007668:Kidney / Q000187:drug effects*; D007672:Kidney Cortex / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000187:drug effects; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D005839:Gentamicins; D007444:Inulin; D002118:Calcium