title: High citrate diet delays progression of renal insufficiency in the ClC-5 knockout mouse model of Dent's disease.
abstract: BACKGROUND
  Dent's disease, an X-linked renal tubular disorder, is characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and progressive renal failure. Dent's disease results from mutations of the voltage-gated chloride channel CLC-5.
  
  
  METHODS
  We studied the effect of zero and high citrate diet on renal function of ClC-5 knockout mice and wild-type mice. The mice were placed in metabolic cages from which the urine was collected. Mice were sacrificed to obtain serum and tissues for analysis.
  
  
  RESULTS
  ClC-5 knockout mice fed zero or high citrate diet had significantly increased urinary calcium excretion compared with wild-type mice fed the same diets. Nine-month-old ClC-5 knockout mice on a zero citrate diet had significantly decreased glomerular filtration rate (GFR), whereas 9-month-old ClC-5 knockout mice on a high citrate diet had normal renal function. ClC-5 knockout mice fed a zero citrate diet had significantly increased tubular atrophy, interstitial fibrosis, cystic changes, and nephrocalcinosis compared to ClC-5 knockout mice fed a high citrate diet. Transforming growth factor-beta1 (TGF-beta1) was significantly increased in 9-month-old ClC-5 knockout mice on zero citrate diet compared to 9-month-old wild-type mice on the same diet.
  
  
  CONCLUSIONS
  High citrate diet preserved renal function and delayed progression of renal disease in ClC-5 knockout mice even in the apparent absence of stone formation. We conclude from this that long-term control of hypercalciuria is an important factor in preventing renal failure in these mice.
authors: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors: Valeriu
authors: V
authors: Cebotaru
authors: Sadhana
authors: S
authors: Kaul
authors: Olivier
authors: O
authors: Devuyst
authors: Hui
authors: H
authors: Cai
authors: Lorraine
authors: L
authors: Racusen
authors: William B
authors: WB
authors: Guggino
authors: Sandra E
authors: SE
authors: Guggino
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D002114:Calcinosis / Q000178:diet therapy / Q000473:pathology / Q000503:physiopathology; D002118:Calcium / Q000652:urine; D018118:Chloride Channels / Q000235:genetics*; D002951:Citrates / Q000494:pharmacology* / Q000652:urine; D003404:Creatinine / Q000097:blood; D004032:Diet; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate; D006863:Hydrogen-Ion Concentration; D007669:Kidney Calculi / Q000178:diet therapy / Q000473:pathology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000178:diet therapy* / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D011188:Potassium / Q000652:urine; D012964:Sodium / Q000652:urine; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
chemical_list: C097503:CLC-5 chloride channel; D018118:Chloride Channels; D002951:Citrates; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D012964:Sodium; D003404:Creatinine; D011188:Potassium; D002118:Calcium