High citrate diet delays progression of renal insufficiency in the ClC-5 knockout mouse model of Dent's disease

Valeriu Cebotaru, Sadhana Kaul, Olivier Devuyst, Hui Cai, Lorraine Racusen, William B. Guggino, Sandra E. Guggino

Research output: Contribution to journalArticle

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-β1 (TGF-β1) 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. Conclusion. 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.

Original languageEnglish (US)
Pages (from-to)642-652
Number of pages11
JournalKidney international
Volume68
Issue number2
DOIs
StatePublished - Aug 1 2005

Keywords

  • Chloride channel
  • Citrate
  • Dent's disease
  • Hypercalciuria
  • Nephrocalcinosis
  • Renal insufficiency

ASJC Scopus subject areas

  • Nephrology

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