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

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.

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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.

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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.

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Correspondence to Vicente E Torres.

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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.”

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Torres, V., Wang, X., Qian, Q. et al. Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease. Nat Med 10, 363–364 (2004). https://doi.org/10.1038/nm1004

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