title: Development of an animal model of nephrocalcinosis via selective dietary sodium and chloride depletion.
abstract: BACKGROUND
  Nephrocalcinosis (NC) is an important clinical problem seen in critically ill preterm 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 or both. A subgroup 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. By 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- and 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.
  
  
  CONCLUSIONS
  Severe ECF volume contraction induced by chronic sodium and chloride depletion appears to play an important role in the pathogenesis of NC.
authors.affiliation: Division of Pediatric Nephrology, Children's Research Institute, Children's National Medical Center, Washington, DC, USA. stuchman@cnmc.org
authors.forename: Shamir
authors.initials: S
authors.lastname: Tuchman
authors.forename: Laureano D
authors.initials: LD
authors.lastname: Asico
authors.forename: Crisanto
authors.initials: C
authors.lastname: Escano
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Bobb
authors.forename: Patricio E
authors.initials: PE
authors.lastname: Ray
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002118:Calcium / Q000652:urine; D002712:Chlorides / Q000378:metabolism*; D004195:Disease Models, Animal; D005665:Furosemide; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009397:Nephrocalcinosis / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D010758:Phosphorus / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000172:deficiency*; D017673:Sodium Chloride, Dietary / Q000378:metabolism*; D013997:Time Factors; D014882:Water-Electrolyte Balance; D015430:Weight Gain
chemical_list: D002712:Chlorides; D017673:Sodium Chloride, Dietary; D010758:Phosphorus; D005665:Furosemide; D012964:Sodium; D002118:Calcium