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

BMC Nephrology

Erling B Pedersen¹  Robert A Fenton²  Jesper N Bech¹  Anna-Ewa O Kulik¹  Frank H Mose¹  Janni M Jensen¹ 

[1] Regional Hospital Jutland West and Aarhus University, Aarhus, Denmark;Department of Biomedicine, Aarhus University, Aarhus, Denmark

关键词: Water;    Sodium;    ENaC;    AQP2;    NKCC2;    Chronic kidney disease;   

Others  :  1082663
DOI  :  10.1186/1471-2369-15-101

 received in 2014-02-27, accepted in 2014-06-11,  发布年份 2014

【 摘 要 】

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 (C_H2O), urinary output (UO), fractional excretion of sodium (FE_Na), 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 FE_Na, 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 C_H2O 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 C_H2O. 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.

【 授权许可】

   
2014 Jensen et al.; licensee BioMed Central Ltd.

【 图 表 】

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