Strategies targeting cAMP signaling in the treatment of polycystic kidney disease

J Am Soc Nephrol. 2014 Jan;25(1):18-32. doi: 10.1681/ASN.2013040398. Epub 2013 Dec 12.


Polycystic kidney disease (PKD) is a leading cause of ESRD worldwide. In PKD, excessive cell proliferation and fluid secretion, pathogenic interactions of mutated epithelial cells with an abnormal extracellular matrix and alternatively activated interstitial macrophages, and the disruption of mechanisms controlling tubular diameter contribute to cyst formation. Studies with animal models suggest that several diverse pathophysiologic mechanisms, including dysregulation of intracellular calcium levels and cAMP signaling, mediate these cystogenic mechanisms. This article reviews the evidence implicating calcium and cAMP as central players in a network of signaling pathways underlying the pathogenesis of PKD and considers the therapeutic relevance of treatment strategies targeting cAMP signaling.

Publication types

  • Review

MeSH terms

  • Animals
  • Antidiuretic Hormone Receptor Antagonists
  • Calcium / metabolism
  • Cell Membrane / metabolism
  • Cell Membrane / pathology
  • Cell Proliferation
  • Clinical Trials as Topic
  • Cyclic AMP / metabolism*
  • Drinking
  • Humans
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Models, Biological
  • Polycystic Kidney Diseases / etiology
  • Polycystic Kidney Diseases / metabolism*
  • Polycystic Kidney Diseases / therapy*
  • Polycystic Kidney, Autosomal Dominant / etiology
  • Polycystic Kidney, Autosomal Dominant / metabolism
  • Polycystic Kidney, Autosomal Dominant / therapy
  • Signal Transduction
  • Somatostatin / analogs & derivatives
  • Somatostatin / therapeutic use


  • Antidiuretic Hormone Receptor Antagonists
  • Somatostatin
  • Cyclic AMP
  • Calcium