Development of an animal model of nephrocalcinosis via selective dietary sodium and chloride depletion

BACKGROUND: Nephrocalcinosis (NC) is an important clinical problem seen in critically ill pre-term neonates treated with loop diuretics. No reliable animal models are available to study the pathogenesis of NC in preterm infants. The purpose of this study was to develop a reproducible and clinically relevant animal model of NC for these patients, and to explore the impact of extracellular fluid (ECF) volume contraction induced by sodium and chloride depletion in this process. METHODS: Three-week old weanling Sprague-Dawley rats were fed diets deficient in either chloride or sodium and chloride. A sub-group of rats from each dietary group was injected daily with furosemide (40 mg/kg; i.p.). RESULTS: Rats fed a control diet, with or without furosemide, or a chloride depleted diet alone, did not develop NC. In contrast, 50% of the rats injected with furosemide and fed the chloride depleted diet developed NC. Moreover, 94% of the rats fed the combined sodium/chloride depleted diet developed NC, independently of furosemide use. NC was associated with the development of severe ECF volume contraction, hypochloremic, hypokalemic metabolic alkalosis, increased phosphaturia, and growth retardation. CONCLUSION: Severe ECF volume contraction induced by chronic sodium and chloride depletion appears to play an important role in the pathogenesis of NC.