Calcimimetic inhibits late-stage cyst growth in ADPKD

Vincent H. Gattone, Xuening (Neal) Chen, Rachel M. Sinders, Mark F. Seifert, Danxia Duan, David Martin, Charles Henley, Sharon Moe

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

In polycystic kidney disease (PKD), genetic mutations in polycystin 1 and 2 lead to defective intracellular trafficking of calcium, thereby decreasing intracellular calcium and altering cAMP signaling to favor proliferation. We hypothesized that calcimimetics, allosteric modulators of the calcium-sensing receptor, would reduce cyst growth by increasing intracellular calcium. We randomly assigned 20-wk-old male rats with a form of autosomal dominant PKD (heterozygote Cy/+) to one of four groups for 14 to 18 wk of treatment: (group 1) no treatment; (group 2) calcimimetic R-568 formulated in the diet; (group 3) R-568 plus calcium-supplemented drinking water (R-568 plus Ca); or (group 4) Ca-supplemented drinking water with a normal diet (Ca). Severity of PKD did not progress in any of the three treatment groups between 34 and 38 wk. Compared with no treatment, cyst growth was unaffected at 34 wk by all treatments, but cyst volume and fibrosis were lower at 38 wk, with both R-568-treated groups demonstrating a greater reduction than calcium alone. Between 34 and 38 wk, the total kidney weight increased by 78% in the control group (P < 0.001) and by 19% in the Ca group (P < 0.01), but did not increase in the R-568 or R-568 plus Ca groups, suggesting inhibition of disease progression despite equivalent suppression of parathyroid hormone. In summary, treatment of hyperparathyroidism halts late-stage progression of rodent cystic kidney disease. The benefit of R-568 alone suggests calcium-sensing receptor modulation may have additional inhibitory effects on late-stage cyst growth resulting from a direct modulation of intracellular calcium.

Original languageEnglish
Pages (from-to)1527-1532
Number of pages6
JournalJournal of the American Society of Nephrology
Volume20
Issue number7
DOIs
StatePublished - Jul 2009

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N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine
Autosomal Dominant Polycystic Kidney
Cysts
Calcium
Growth
Calcium-Sensing Receptors
Polycystic Kidney Diseases
Drinking Water
Diet
Cystic Kidney Diseases
Hyperparathyroidism
Heterozygote
Parathyroid Hormone
Disease Progression
Rodentia
Fibrosis
Kidney
Weights and Measures

ASJC Scopus subject areas

  • Nephrology

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Calcimimetic inhibits late-stage cyst growth in ADPKD. / Gattone, Vincent H.; Chen, Xuening (Neal); Sinders, Rachel M.; Seifert, Mark F.; Duan, Danxia; Martin, David; Henley, Charles; Moe, Sharon.

In: Journal of the American Society of Nephrology, Vol. 20, No. 7, 07.2009, p. 1527-1532.

Research output: Contribution to journalArticle

Gattone, VH, Chen, XN, Sinders, RM, Seifert, MF, Duan, D, Martin, D, Henley, C & Moe, S 2009, 'Calcimimetic inhibits late-stage cyst growth in ADPKD', Journal of the American Society of Nephrology, vol. 20, no. 7, pp. 1527-1532. https://doi.org/10.1681/ASN.2008090927
Gattone, Vincent H. ; Chen, Xuening (Neal) ; Sinders, Rachel M. ; Seifert, Mark F. ; Duan, Danxia ; Martin, David ; Henley, Charles ; Moe, Sharon. / Calcimimetic inhibits late-stage cyst growth in ADPKD. In: Journal of the American Society of Nephrology. 2009 ; Vol. 20, No. 7. pp. 1527-1532.
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AU - Duan, Danxia

AU - Martin, David

AU - Henley, Charles

AU - Moe, Sharon

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