Jensen Janni M, Mose Frank H, Kulik Anna-Ewa O, Bech Jesper N, Fenton Robert A, Pedersen Erling B
Department of Medical Research, Holstebro Hospital, University Clinic in Nephrology and Hypertension, Laegaardvej 12, 7500 Holstebro, Denmark.
BMC Nephrol. 2014 Jun 26;15:101. doi: 10.1186/1471-2369-15-101.
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.
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.
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.
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.
Clinical trial no: NCT01623661. Date of trial registration: 18.06.2012.
慢性肾脏病（CKD）患者的肾脏对钠和水的处理存在异常。本研究的目的是验证水通道蛋白2（AQP2）、钠-钾-2-氯化物转运体（NKCC2）和/或上皮钠通道（ENaC）的异常活性导致这一现象的假说。
比较23例CKD患者和24例健康对照者在基线时及输注3%盐水后的情况。进行了以下测量：尿液中AQP2（u-AQP2）、NKCC2（u-NKCC2）、ENaC（u-ENaCγ）的浓度，通过51Cr-EDTA清除率估算的肾小球滤过率（GFR）、自由水清除率（CH2O）、尿量（UO）、钠分数排泄率（FENa）、血浆中抗利尿激素（AVP）、肾素（PRC）、血管紧张素II（ANG II）、醛固酮（Aldo）的浓度以及体液量。
基线时，CKD患者的GFR为34 ml/min，对照组为89 ml/ml。u-AQP2、u-NKCC2或u-ENaCγ无显著差异，但CKD患者的FENa、p-Aldo和p-AVP高于对照组。对高渗盐水的反应中，CKD患者的CH2O和UO的降低减弱。与对照组相比，CKD患者的U-AQP2升高更明显。此外，CKD患者的u-NKCC2升高，而对照组的u-NKCC2降低。体液量无显著差异。
对高渗盐水的反应中，u-NKCC2升高，提示CKD患者通过NKCC2的钠重吸收增加。尽管CH2O的降低减弱，但CKD患者的U-AQP2升高更明显。因此，尽管p-AVP和p-Aldo水平较高，但由于肾小管反应缺陷，肾脏只能部分代偿和抵消急性容量扩张。
临床试验编号：NCT01623661。试验注册日期：2012年6月18日。
