Effect of thiazide on established furosemide-induced nephrocalcinosis in the young rat

Abstract 

A previous study on furosemide-induced nephrocalcinosis (NC) showed only partial resolution of the calcifications after discontinuation of the diuretic. We investigated whether treatment with chlorothiazide (CTZ) will expedite the resolution of established furosemide-induced NC. Seventy-eight weanling male Sprague-Dawley rats were divided into eight groups. Three groups were studied for 1 week: A, control; B, furosemide 40 mg/kg per 24 h; C, CTZ 100 mg/kg per 24 h. Five groups were studied for 5 weeks: D, control; E, F, G, furosemide 40 mg/kg per 24 h for 1 week followed by 4 weeks of observation (E), CTZ 50 mg/kg per 24 h (F), and CTZ 100 mg/kg per 24 h (G) and; and CTZ 100 mg/kg per 24 h (H) for 5 weeks. At the end of each study period urine and blood were collected, one kidney was studied histologically and the contralateral ashed for quantitative calcium (Ca) analysis. Animals in group B developed NC with a kidney Ca content of 1,844±203 µg/g dry tissue compared with group A 248±86 (P<0.05) and group C 256±56 (P<0.05). There were no differences among the three groups with regard to creatinine clearance, urine phosphate (P) or Ca excretion, although the latter tended to be lower in group C. Animals in group E showed a reduction in the magnitude of NC, with kidney Ca of 550±398 µg/g dry tissue, which was lower than in group B (P<0.05) but still higher than in groups D (140±27) (P<0.05) or H (162±63) (P<0.05). Kidney Ca content in groups F (497±142) and G (489±271 µg/g dry tissue) was similar to that in group E. There were no differences among the five groups with regard to creatinine clearance or urine P excretion. Urine Ca excretion was significantly lower in groups F and G than groups D and E. We conclude that once established, NC caused by furosemide is not affected by CTZ therapy in spite of the anticalciuric property of the latter.