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NDT Advance Access published online on June 23, 2009

Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp303
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© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org



Osmomediated natriuresis in humans: the role of vasopressin and tubular calcium sensing

Ewout J. Hoorn, M. Carola Zillikens, Huibert A. P. Pols, Alexander H. Jan Danser, Frans Boomsma and Robert Zietse

Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

Correspondence and offprint requests to: Ewout J. Hoorn; E-mail: ejhoorn{at}gmail.com



  Abstract

Background. The aim was to investigate the unknown mechanism of osmomediated natriuresis. This is the phenomenon by which hypertonic saline (HS) produces a larger natriuresis than isotonic saline (IS), despite the same sodium content.

Methods. Seven healthy volunteers first received HS and then IS (both 3.85 mmol sodium/kg). To investigate the role of calcium metabolism, four patients received HS, two with an activating mutation (ADH) and two with an inactivating mutation (FHH) of the calcium-sensing receptor (CaSR).

Results. In healthy volunteers, HS produced mild hypernatraemia, a 4-fold rise in vasopressin (to 2.2 ± 0.85 pg/mL) and a 3-fold rise in natriuresis compared with a 1.5-fold rise with IS (P = 0.002). This confirmed osmomediated natriuresis. HS caused calciuresis to increase 1.4-fold and then reduced it 1.4-fold, whereas IS failed to increase calciuresis and caused it to fall 3.7-fold (P = 0.05). Natriuresis and calciuresis in ADH patients were similar to healthy volunteers receiving HS, whereas a blunted response was seen in FHH patients. Patient vasopressin levels did not exceed 1.3 pg/mL and changes from baseline were variable. In one FHH patient, a 3-fold rise in vasopressin did not prevent the blunted natriuresis and calciuresis. In one ADH patient, natriuresis and calciuresis were similar to healthy volunteers despite a 1.7-fold fall in vasopressin.

Conclusions. Our data suggest that not only vasopressin (possibly via its V1a receptor), but also the CaSR (which is sensitive to high sodium concentrations) may play a role in osmomediated natriuresis. These results shed new light on osmomediated natriuresis and suggest roles for the CaSR beyond calcium regulation.

Keywords: calcium-sensing receptor; hypernatraemia; parathyroid hormone; thick ascending limb

Received for publication: 7. 2.09
Accepted in revised form: 28. 5.09


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