Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease

Article metrics

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a leading cause of end-stage renal disease. The vasopressin V2 receptor (VPV2R) antagonist OPC31260 has been effective in two animal models of PKD with pathologies that are probably related. Here we show, in a mouse model of ADPKD (Pkd2−/tm1Som), a similar cellular phenotype and response to OPC31260 treatment, with reduction of renal cyclic AMP (cAMP) levels, prevention of renal enlargement, marked inhibition of cystogenesis and protection of renal function.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Renal cAMP concentrations, aquaporin-2 and VPV2R expression, and immunohistochemistry for tubular markers.
Figure 2: Effects of OPC32160 on development of PKD in Pkd2−/tm1Som mice.

References

  1. 1

    Koulen, P. et al. Nat. Cell Biol. 4, 191–197 (2002).

  2. 2

    Nauli, S.M. et al. Nat. Genet. 33, 129–137 (2003).

  3. 3

    Qian, Q. et al. Hum. Mol. Genet. 12, 1875–1880 (2003).

  4. 4

    Chabardes, D., Imbert-Teboul, M. & Elalouf, J.M. Cell. Signal. 11, 651–663 (1999).

  5. 5

    Wallace, D.P., Rome, L.A., Sullivan, L.P. & Grantham, J.J. Am. J. Physiol. Renal Physiol. 280, F1019–F1029 (2001).

  6. 6

    Ye, M. & Grantham, J. N. Engl. J. Med. 329, 310–313 (1993).

  7. 7

    Yamaguchi, T. et al. Kidney Int. 57, 1460–1471 (2000).

  8. 8

    Gattone, V.H., Wang, X., Harris, P.C. & Torres, V.E. Nat. Med. 9, 1323–1326 (2003).

  9. 9

    Wu, G. et al. Cell 93, 177–188 (1998).

  10. 10

    Verani, R.R. & Silva, F.G. Mod. Pathol. 1, 457–463 (1988).

  11. 11

    Gabow, P. et al. Kidney Int. 35, 675–680 (1989).

  12. 12

    Sweeney, W.E., Jr. et al. Am. J. Physiol. Cell Physiol. 281, C1695–C1705 (2001).

  13. 13

    Yamaguchi, T., Wallace, D.P., Grantham, J.J. & Calvet, J.P. J. Am. Soc. Nephrol. 13, 105A (2002).

  14. 14

    Thibonnier, M., Coles, P., Thibonnier, A. & Shoham, M. Annu. Rev. Pharmacol. Toxicol. 41, 175–202 (2001).

Download references

Acknowledgements

This work was supported by National Institutes of Health grant DK44863 (V.E.T.) and by a grant from the Polycystic Kidney Disease Foundation (V.H.G.). OPC31260 was a gift from Otsuka Pharmaceutical. Technical assistance was provided by Ming Li.

Author information

Correspondence to Vicente E Torres.

Ethics declarations

Competing interests

V.H.G. is listed as the inventor on the US patent, held by the University of Kansas Medical Center, entitled, “Treatment of polycystic kidney disease using vasopressin V2 receptor antagonists.”

Supplementary information

Supplementary Table 1 (PDF 22 kb)

Rights and permissions

Reprints and Permissions

About this article

Further reading