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BMC Nephrology
Published in: BMC Nephrology 1/2014

Open Access 01-12-2014 | Research article

Abnormal urinary excretion of NKCC2 and AQP2 in response to hypertonic saline in chronic kidney disease: an intervention study in patients with chronic kidney disease and healthy controls

Authors: Janni M Jensen, Frank H Mose, Anna-Ewa O Kulik, Jesper N Bech, Robert A Fenton, Erling B Pedersen

Published in: BMC Nephrology | Issue 1/2014

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Abstract

Background

Renal handling of sodium and water is abnormal in chronic kidney disease (CKD). The aim of this study was to test the hypothesis that abnormal activity of the aquaporin-2 water channels (AQP2), the sodium-potassium-2chloride transporter (NKCC2) and/or the epithelial sodium channels (ENaC) contribute to this phenomenon.

Methods

23 patients with CKD and 24 healthy controls at baseline and after 3% saline infusion were compared. The following measurements were performed: urinary concentrations of AQP2 (u-AQP2), NKCC2 (u-NKCC2), ENaC (u-ENaCγ), glomerular filtration rate (GFR) estimated by 51Cr-EDTA clearance, free water clearance (CH2O), urinary output (UO), fractional excretion of sodium (FENa), plasma concentrations of AVP, renin (PRC), Angiotensin II (ANG II), Aldosterone (Aldo) and body fluid volumes.

Results

At baseline, GFR was 34 ml/min in CKD patients and 89 ml/ml in controls. There were no significant differences in u-AQP2, u-NKCC2 or u-ENaCγ, but FENa, p-Aldo and p-AVP were higher in CKD patients than controls. In response to hypertonic saline, patients with CKD had an attenuated decrease in CH2O and UO. A greater increase in U-AQP2 was observed in CKD patients compared to controls. Furthermore, u-NKCC2 increased in CKD patients, whereas u-NKCC2 decreased in controls. Body fluid volumes did not significantly differ.

Conclusions

In response to hypertonic saline, u-NKCC2 increased, suggesting an increased sodium reabsorption via NKCC2 in patients with CKD. U-AQP2 increased more in CKD patients, despite an attenuated decrease in CH2O. Thus, though high levels of p-AVP and p-Aldo, the kidneys can only partly compensate and counteract acute volume expansion due to a defective tubular response.

Trial registration

Clinical trial no: NCT01623661. Date of trial registration: 18.06.2012.
Appendix
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Metadata
Title
Abnormal urinary excretion of NKCC2 and AQP2 in response to hypertonic saline in chronic kidney disease: an intervention study in patients with chronic kidney disease and healthy controls
Authors
Janni M Jensen
Frank H Mose
Anna-Ewa O Kulik
Jesper N Bech
Robert A Fenton
Erling B Pedersen
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2014
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/1471-2369-15-101

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