FUROSEMIDE EFFECTS ON NEWBORN RENAL & BONE CALCIUM METABOLISM

Furosemide diuretics are commonly used in neonatal intensive care. Recent anecdotal reports have appeared of preterm infants who develop renal calcification & osteopenia on chronic high dose furosemide therapy. The mechanisms for development of these possible complications in infancy is unclear. We hypothesize that furosemide diuretics result directly in hypercalciuria, nephrocalcinosis, secondary hyperparathy-roidism & decreased bone mineral content. Newborn rats were randomized from day four into control & treated groups for a 28 day study. Grp. 1, placebo; Grp. 2, daily 5 mg/kg of furosemide; Grp 3, 15 mg/kg of furosemide. By analysis of variance, urinary calcium increased from 7.81 to 11.25 to 20.35 mg/dl for the three respective groups (p< .05). Urinary Mg also increased from 13.1 to 14.1 to 19.3 mg/dl. Urinary P did not increase. Renal Ca ash content of treatment grps. were significantly increased (6 of 25 & 6 of 26) beyond control 95% limit. Chi-square p<.05. Bone weight of tibias was decreased from .21 to .17, .16 gs. (p<.01), as was ash weight .13, .11, .10 gs. (p<.05), in association with decreases in body weight of 68, 62, 57 gs. Bone Ca & body weight were correlated (p .01). Serum Ca, Mg, P, & parathyroid hormone concentrations (mid molecule 44-68 radioimmunoassay, rat standard, CV 9%), were not different among grps. Thus, furosemide in newborn rats results in increased urinary Ca, increased renal Ca content, decreased bone mineral, decreased body weight & no changes in serum Ca, Mg, P or parathyroid hormone. We speculate that the effect of furosemide therapy in the newborn on Ca metabolism is directly related to increased Ca loss in the urine.