Header

UZH-Logo

Maintenance Infos

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


Devuyst, Olivier; Torres, Vicente E (2013). Osmoregulation, vasopressin, and cAMP signaling in autosomal dominant polycystic kidney disease. Current Opinion in Nephrology and Hypertension, 22(4):459-470.

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.

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.

Statistics

Citations

18 citations in Web of Science®
17 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

70 downloads since deposited on 22 Jul 2013
16 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2013
Deposited On:22 Jul 2013 06:31
Last Modified:05 Apr 2016 16:52
Publisher:Lippincott, Williams & Wilkins
ISSN:1062-4821
Additional Information:This is a non-final version of an article published in final form in Devuyst, Olivier; Torres, Vicente E (2013). Osmoregulation, vasopressin, and cAMP signaling in autosomal dominant polycystic kidney disease. Current Opinion in Nephrology and Hypertension, 22(4):459-470.
Publisher DOI:https://doi.org/10.1097/MNH.0b013e3283621510
PubMed ID:23736843

Download

Preview Icon on Download
Preview
Content: Accepted Version
Filetype: PDF
Size: 452kB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations