Modification of experimental gentamicin nephrotoxicity by selective parathyroidectomy.

Abstract

Dietary calcium loading reduces gentamicin nephrotoxicity in rats. Since parathyroid hormone increases renal brush border membrane anionic phospholipids, the putative gentamicin receptors, the effects of selective parathyroidectomy on gentamicin nephrotoxicity were examined. Male Fisher 344 rats underwent parathyroidectomy or sham surgery. All animals were fed a diet containing 0.5% calcium for 2 wk prior to gentamicin, 20 mg/kg twice daily for 6 and 10 days. Other parathyroidectomized rats were fed a 4% calcium diet for 2 wk and treated similarly with gentamicin On day 6, serum creatinine (mg/100 ml) was 2.0 +/- 0.9 in the sham-operated animals, 1.7 +/- 1.6 in the parathyroidectomized animals on the 0.5% diet, and 0.8 +/- 0.1 in the parathyroidectomized animals on the 4% diet. By 10 days, the sham-operated animals had creatinine values of 6.3 +/- 1.6 (mg/100 ml) compared with 1.7 +/- .9 in the parathyroidectomized animals on the same diet and 0.8 +/- 0.2 in the 4% diet animals. More severe tubular necrosis was present in the sham-operated compared with the parathyroidectomized animals. High calcium diet in the parathyroidectomized animals produced structural and functional protection from gentamicin nephrotoxicity. Human parathyroid hormone (1-34) 20 IU twice daily given subcutaneously to a separate group of parathyroidectomized rats, eliminated the protective effect of parathyroidectomy on renal structure and function. Parathyroidectomy modifies experimental gentamicin nephrotoxicity. The additional protective effect of dietary calcium loading may be independent of parathyroid ablation.