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
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
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DOI：
10.1186/1471-2369-15-101
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发表时间：
2014-06-26
期刊：
影响因子：
2.3
通讯作者：
Pedersen, Erling B.
中科院分区：
文献类型：
--
作者：
Jensen, Janni M.;Mose, Frank H.;Pedersen, Erling B.
背景：慢性肾脏病（CKD）患者肾脏对水和钠的处理异常。本研究的目的是检验水通道蛋白-2水通道（AQP 2），钠-钾-2-氯转运蛋白（NKCC 2）和/或上皮钠通道（ENaC）的异常活动有助于这种现象的假设。方法：23例CKD患者和24例健康对照组在基线和3%生理盐水输注后进行了比较。进行了以下测量：尿AQP 2（u-AQP 2）、NKCC 2（u-NKCC 2）、ENaC浓度（u-ENaC γ）、通过Cr-51-EDTA清除率估计的肾小球滤过率（GFR）、游离水清除率（C-H2O）、尿量（UO）、钠排泄分数（FENa）、AVP、肾素（PRC）、血管紧张素II（ANG II）的血浆浓度，结果：基线时，CKD患者GFR为34 ml/min，对照组为89 ml/ml。CKD组u-AQP 2、u-NKCC 2和u-ENaC γ水平均无显著性差异，但FENa、p-Aldo和p-AVP水平均高于对照组。高渗盐水治疗后，CKD患者的CH 2 O和UO减少。与对照组相比，在CKD患者中观察到U-AQP 2的更大增加。此外，CKD患者中u-NKCC 2增加，而对照组中u-NKCC 2减少。体液量没有显着different.Conclusions：在响应高渗盐水，u-NKCC 2增加，这表明增加钠重吸收通过NKCC 2在CKD患者。CKD患者中U-AQP 2增加更多，尽管CH 2 O减少减弱。因此，虽然高水平的p-AVP和p-Aldo，肾脏只能部分补偿和抵消由于有缺陷的肾小管反应引起的急性体积膨胀。
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-ENaC gamma), glomerular filtration rate (GFR) estimated by Cr-51-EDTA clearance, free water clearance (C-H2O), 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-ENaC gamma, 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.