Development of Animal Model of Nephrolithiasis

Kim, Hyeon Hoe; Jo, Moonki; Kwak, Cheol; Jeon, Seong Soo; Kim, Si Whang

Abstract

To develop an animal model of nephrolithiasis similar to the pattern of human renal stone disease, we adopted a protocol of administration of stone substrates along with induction of renal tubular injuries. Male Wister rats fed with 3% ammonium oxalate containing chows with or without additional 40 mg/kg/day of gentamicin for 8 days were compared with those fed with normal chows. On dissecting microscopic examination, rats receiving oxalate and gentamicin showed more crystals and plaques than rats receiving oxalate only, both in 15 days and 22 days after feeding, and most of the crystals were located at renal papilla. Average score of crystal abundance was 0.4, 1.15, respectively in rats receiving oxalate only and oxalate plus gentamicin after 15 days of feeding, and 0.9 and 1.55, respectively after 22 days. Little crystals were found in rats fed with normal chow with or without gentamicin. Urinary excretion of tubular epithelial brush border enzyme, gamma-glutamyl transpeptidase(GGT), was increased by gentamicin administration whereas creatinine clearance rate was not changed. Urinary excretion of oxalate was unchanged, but calcium and uric acid was markedly decreased in rats fed with oxalate and formed crystals, and citrate and magnesium excretion was also decreased. These results indicate that administration of oxalate along with inducing renal tubular damages by subcutaneous injection of gentamicin seems to form crystals and plaques in the kidney more rapidly and abundantly than feeding with oxalate alone.