title: Mechanism of chronic hypercalciuria with furosemide: increased calcium absorption.
abstract: Furosemide produces chronic hypercalciuria. The source of the additional urinary calcium is not known but must be either bone mineral or calcium absorbed by the intestine. Without bone calcium dissolution or increased absorption the filtered load of calcium would fall and urinary calcium excretion would return to pretreatment levels. To determine whether furosemide alters intestinal calcium absorption, we fed furosemide (75 mg . kg body-1 wt . day-1) to 11 rats eating 15 g/day of a 0.60% calcium diet. Compared with 11 control rats, furosemide increased urine calcium (15.6 +/- 0.8 mg/5 days vs. 4.1 +/- 0.3, P less than 0.001). Fecal calcium excretion fell (194 +/- 7 mg/5 days vs. 223 +/- 12, P less than 0.05), indicating an increase in intestinal calcium absorption sufficient to sustain the hypercalciuria. The increase in absorption occurred without an increase in the level of serum 1,25-dihydroxycholecalciferol (180 +/- 20 pg/ml vs. 220 +/- 16, furosemide vs. control, respectively, P = NS). To determine whether the intestinal effect of furosemide persists after the initial sodium diuresis abates, we analyzed only the last 3 days of balance. Again, rats fed furosemide had increased urine excretion and intestinal absorption of calcium, so that net calcium balance was not different from that of controls. Twelve additional rats were fed a 0.02% calcium diet to which 35 mg . kg body wt-1 . day-1 of furosemide was added. Compared with eleven controls, urine calcium increased and fecal calcium excretion again fell, but balance was not different. Chronic administration of furosemide increases intestinal calcium absorption enough to permit urine calcium excretion to remain elevated without the necessity for bone dissolution.
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000652:urine*; D004231:Diuresis / Q000187:drug effects; D005665:Furosemide / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects; D007408:Intestinal Absorption / Q000187:drug effects*; D008274:Magnesium / Q000652:urine; D008297:Male; D010758:Phosphorus / Q000652:urine; D051381:Rats; D013997:Time Factors
chemical_list: D010758:Phosphorus; D005665:Furosemide; D002117:Calcitriol; D008274:Magnesium; D002118:Calcium