Osmoregulation, vasopressin, and cAMP signaling in autosomal dominant polycystic kidney disease

Olivier Devuyst, Vicente E. Torres

Research output: Contribution to journalReview article

39 Scopus citations

Abstract

Purpose of review: Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited nephropathy. This review will focus on the vasopressin and 3′-5′-cyclic adenosine monophosphate (cAMP) signaling pathways in ADPKD and will discuss how these insights offer new possibilities for the follow-up and treatment of the disease. Recent findings: Defective osmoregulation is an early manifestation of ADPKD and originates from both peripheral (renal effect of vasopressin) and central (release of vasopressin) components. Copeptin, which is released from the vasopressin precursor, may identify ADPKD patients at risk for rapid disease progression. Increased levels of cAMP in tubular cells, reflecting modifications in intracellular calcium homeostasis and abnormal stimulation of the vasopressin V2 receptor (V2R), play a central role in cystogenesis. Blocking the V2R lowers cAMP in cystic tissues, slows renal cystic progression and improves renal function in preclinical models. A phase III clinical trial investigating the effect of the V2R antagonist tolvaptan in ADPKD patients has shown that this treatment blunts kidney growth, reduces associated symptoms and slows kidney function decline when given over 3 years. Summary: These advances open perspectives for the understanding of cystogenesis in ADPKD, the mechanisms of osmoregulation, the role of polycystins in the brain, and the pleiotropic action of vasopressin.

Original languageEnglish (US)
Pages (from-to)459-470
Number of pages12
JournalCurrent opinion in nephrology and hypertension
Volume22
Issue number4
DOIs
StatePublished - Jul 1 2013

Keywords

  • Collecting duct
  • Osmoregulation
  • Polycystins
  • V2 receptor antagonist
  • Vasopressin

ASJC Scopus subject areas

  • Internal Medicine
  • Nephrology

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