Salt supplementation, growth, and nephrocalcinosis in the furosemide-treated weanling rat.
OBJECTIVE
Furosemide treatment in the human neonate is associated with sodium depletion, growth retardation, hypercalciuria and nephrocalcinosis. Dietary sodium intake is known to directly influence urinary calcium excretion. The objectives of this study were to create a rat model of furosemide-induced nephrocalcinosis and to test the effects of dietary sodium supplementation on growth, electrolyte balance, calciuria, and renal calcifications.


METHODS
Initially, 18 weanling Sprague-Dawley rats were randomly divided into three groups. Groups A (control) and B were fed a basal diet. Group C was fed a sodium-enriched diet. Groups B and C received furosemide (40 mg/kg) intraperitoneally daily for 28 days. At the end of the study, serum, urine, and kidney samples were obtained for biochemical and histologic analyses. The three groups were then compared for differences in growth, electrolyte homeostasis, calcium excretion and nephrocalcinosis. Subsequently an additional 15 rats were studied to confirm our findings regarding urinary calcium excretion and kidney calcifications.


RESULTS
Treatment with furosemide without sodium supplementation (group B) resulted in decreased weight gain compared with group A (137.5 +/- 12.9 vs 154.0 +/- 10.6 g; p < 0.05), hypokalemia (3.7 +/- 0.1 vs. 4.4 +/- 0.4 mEq/l; p < 0.05), and nephrocalcinosis (187.1 +/- 155 vs. 18.8 +/- 6.9 micrograms Ca/g dry kidney; p < 0.05). Sodium supplementation (group C) normalized weight gain and corrected electrolyte abnormalities without increasing calciuria or nephrocalcinosis.


CONCLUSIONS
We conclude that in this animal model, chronic furosemide treatment results in growth failure and development of nephrocalcinosis. Sodium supplementation protects against the deleterious effects of furosemide on weight gain and electrolyte homeostasis with no adverse effect on nephrocalcinosis.
Gratny
L L
LL
Division of Neonatology, Children's Mercy Hospital, University of Missouri-Kansas City, USA.
Ringer
K
K
Hall
R T
RT
Alon
U S
US
D000818:Animals; D002118:Calcium / Q000652:urine; D004573:Electrolytes / Q000378:metabolism; D005665:Furosemide / Q000633:toxicity*; D006706:Homeostasis; D009397:Nephrocalcinosis / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D014886:Weaning; D015430:Weight Gain
D004573:Electrolytes; D012982:Sodium, Dietary; D005665:Furosemide; D002118:Calcium