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Pediatric Nephrology

, Volume 33, Issue 3, pp 395–408 | Cite as

Expanding the role of vasopressin antagonism in polycystic kidney diseases: From adults to children?

  • Peter Janssens
  • Caroline Weydert
  • Stephanie De Rechter
  • Karl Martin Wissing
  • Max Christoph Liebau
  • Djalila Mekahli
Educational Review

Abstract

Polycystic kidney disease (PKD) encompasses a group of genetic disorders that are common causes of renal failure. The two classic forms of PKD are autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic kidney disease (ADPKD). Despite their clinical differences, ARPKD and ADPKD share many similarities. Altered intracellular Ca2+ and increased cyclic adenosine monophosphate (cAMP) concentrations have repetitively been described as central anomalies that may alter signaling pathways leading to cyst formation. The vasopressin V2 receptor (V2R) antagonist tolvaptan lowers cAMP in cystic tissues and slows renal cystic progression and kidney function decline when given over 3 years in adult ADPKD patients. Tolvaptan is currently approved for the treatment of rapidly progressive disease in adult ADPKD patients. On the occasion of the recent initiation of a clinical trial with tolvaptan in pediatric ADPKD patients, we aim to describe the most important aspects in the literature regarding the AVP-cAMP axis and the clinical use of tolvaptan in PKD.

Keywords

Polycystic kidney disease ADPKD ARPKD Vasopressin Tolvaptan cAMP 

Abbreviations

[cAMP]i

Intracellular cAMP concentration

[Ca2+]i

Intracellular calcium concentration

AC

Adenylyl cyclase

ADPKD

Autosomal-dominant polycystic kidney disease

ARPKD

Autosomal-recessive polycystic kidney disease

AQP2

Aquaporin 2

AVP

Vasopressin

Ca2+

Calcium

cAMP

Cyclic adenosine monophosphate

CD

Collecting duct

CFTR

Cystic fibrosis transmembrane conductance regulator

eGFR

Estimated glomerular filtration rate

ERK

Extracellular signal-regulated kinase

ESRD

End-stage renal disease (ESRD)

FC

Fibrocystin

FDA

Food and drug administration

GSK3β

Glycogen synthase kinase-3

MAPK

Mitogen-activated protein kinase

mTOR

Mammalian target of rapamycin

PC1

Polycystin-1

PC2

Polycystin-2

PCP

Planar-cell polarity

PDE

Phosphodiesterase

PKA

Protein kinase A

PKD

Polycystic kidney disease

SOCS3

Suppressor of cytokine signaling 3

STAT3

Signal transducer and activator of transcription 3

STIM1

Stromal interaction molecule 1

TKV

Total kidney volume

Uosm

Urine osmolality

V2R

Vasopressin V2 receptor

Notes

Acknowledgements

MCL receives funding support from the Köln Fortune Program of the Medical Faculty and from the Center for Molecular Medicine of the University of Cologne, as well as from the Marga and Walter Boll Foundation and the German Federal Ministry for Education and Research (Grant No. 01GM1515E, NEOCYST consortium). SDR is supported by the Fund for Scientific Research, Flanders 11M5214N. DM is supported by the Clinical Research Fund of UZ Leuven, the Fund for Scientific Research G0B1313N, and a research grant from the European Society for Pediatric Nephrology.

Compliance with ethical standards

Conflict of interest statement

None to declare.

Supplementary material

467_2017_3672_MOESM1_ESM.docx (37 kb)
ESM 1 (DOCX 36 kb)

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Copyright information

© IPNA 2017

Authors and Affiliations

  1. 1.Laboratory of PediatricsUniversity Hospitals LeuvenLeuvenBelgium
  2. 2.Department of NephrologyUniversity Hospitals BrusselBrusselBelgium
  3. 3.Department of Pediatric NephrologyUniversity Hospitals LeuvenLeuvenBelgium
  4. 4.Pediatric Nephrology, Department of Pediatrics and Center for Molecular MedicineUniversity Hospital of CologneCologneGermany
  5. 5.Department II of Internal MedicineUniversity Hospital of CologneCologneGermany
  6. 6.Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD) and Systems Biology of Ageing Cologne (Sybacol)University of CologneCologneGermany

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