Calcimimetics inhibit renal pathology in rodent nephronophthisis

Xuening (Neal) Chen, Sharon Moe, Tracy Eggleston-Gulyas, Xianming Chen, William D. Hoffmeyer, Robert Bacallao, Brittney-Shea Herbert, Vincent H. Gattone

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The development and progression of renal cysts appears to be driven by reduced cellular calcium and increased cyclic adenosine monophosphate (cAMP) from G-protein-coupled receptors. To test whether treatment with a calcimimetic that stimulates the G-protein-coupled calcium-sensing receptor might normalize cystic epithelial cell intracellular calcium and cAMP, thereby inhibiting cyst progression, we used pcy mice. These animals develop cysts principally in the collecting duct, as do humans with nephronophthisis (NPHP). We administered the calcimimetic R-568 mixed in their food at early or late stages in the pathogenesis of cyst formation. The treatment reduced cyst enlargement, and the early treatment inhibited development of renal fibrosis. Although the effect of later treatment was more modest, both stages of the disease responded positively to treatment. Additionally, R-568 decreased total kidney cAMP in the pcy mice and, in vitro, decreased cAMP levels and cell proliferation, while increasing intracellular calcium in immortalized human autosomal recessive polycystic kidney disease renal epithelial cells. The latter two effects were unique to R-568 and not replicated by raising extracellular calcium. Thus, treating pcy mice with R-568 was effective in reducing cyst progression in this rodent model of NPHP. Direct studies will be needed to determine whether these results can be applied to the human disease.

Original languageEnglish
Pages (from-to)612-619
Number of pages8
JournalKidney International
Volume80
Issue number6
DOIs
StatePublished - Sep 2 2011

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N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine
Cysts
Rodentia
Pathology
Kidney
Cyclic AMP
Calcium
Autosomal Recessive Polycystic Kidney
Epithelial Cells
Calcium-Sensing Receptors
G-Protein-Coupled Receptors
GTP-Binding Proteins
Fibrosis
Cell Proliferation
Food

Keywords

  • calcium-sensing receptor
  • polycystic kidney disease
  • renal fibrosis
  • renal pathology

ASJC Scopus subject areas

  • Nephrology

Cite this

Calcimimetics inhibit renal pathology in rodent nephronophthisis. / Chen, Xuening (Neal); Moe, Sharon; Eggleston-Gulyas, Tracy; Chen, Xianming; Hoffmeyer, William D.; Bacallao, Robert; Herbert, Brittney-Shea; Gattone, Vincent H.

In: Kidney International, Vol. 80, No. 6, 02.09.2011, p. 612-619.

Research output: Contribution to journalArticle

Chen, Xuening (Neal) ; Moe, Sharon ; Eggleston-Gulyas, Tracy ; Chen, Xianming ; Hoffmeyer, William D. ; Bacallao, Robert ; Herbert, Brittney-Shea ; Gattone, Vincent H. / Calcimimetics inhibit renal pathology in rodent nephronophthisis. In: Kidney International. 2011 ; Vol. 80, No. 6. pp. 612-619.
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