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Vasopressin directly regulates cyst growth in polycystic kidney disease

Xiaofang Wang1, Yanhong Wu, Christopher J Ward

  • 1Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

Journal of the American Society of Nephrology : JASN
|November 23, 2007
PubMed

Insights

Arginine vasopressin (AVP) drives cyst growth in polycystic kidney disease (PKD). Blocking the AVP V2 receptor inhibits cystogenesis, suggesting V2 receptor antagonists are promising for PKD treatment.

Area of Science:

  • Nephrology
  • Genetics
  • Pharmacology

Background:

  • Polycystic kidney diseases (PKD) are genetic disorders leading to kidney failure.
  • Arginine vasopressin (AVP) V2 receptor antagonists show potential in animal models by reducing cyst growth.
  • The precise role of AVP in PKD cystogenesis requires further elucidation.

Purpose of the Study:

  • To confirm the protective effect of AVP V2 receptor antagonists is due to AVP antagonism.
  • To investigate the role of AVP in modulating cystogenesis in PKD models.
  • To provide evidence supporting clinical trials of V2 receptor antagonists for PKD.

Main Methods:

  • Generation of PCK (Pkhd1(-/-)) and Brattleboro (AVP(-/-)) rat crosses to create rats with PKD and varying AVP levels.
  • Measurement of renal cyclic adenosine monophosphate (cAMP) levels at 10 and 20 weeks.
  • Administration of a V2 receptor agonist to assess its impact on cystogenesis and renal cAMP.

Main Results:

  • PCK AVP(-/-) rats exhibited significantly lower renal cAMP and inhibited cystogenesis compared to PCK AVP(+/+) and PCK AVP(+/-) rats.
  • The V2 receptor agonist increased renal cAMP and exacerbated cystogenesis in PCK rats, while not affecting wild-type rats.
  • These findings demonstrate AVP as a key modulator of cystogenesis in PKD.

Conclusions:

  • AVP is a critical factor in the development and progression of polycystic kidney disease.
  • Inhibition of AVP signaling via V2 receptor antagonism effectively suppresses cystogenesis.
  • These results strongly support the clinical investigation of V2 receptor antagonists for treating PKD.

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