University Clinic in Nephrology and Hypertension, Regional Hospital West Jutland and University of Aarhus, Holsstebro, Denmark.
BMC Nephrol. 2020 Aug 31;21(1):379. doi: 10.1186/s12882-020-02043-w.
Concentration of the urine is primarily regulated via vasopressin dependent aquaporin-2 water channels in the apical membrane of kidney principal cells. It is unclear whether urine concentration ability in ADPKD differs from other patients with similar degree of impaired renal function (non-ADPKD patients). The purpose of this case control study was to measure urine concentration ability in ADPKD patients compared to non-ADPKD patients and healthy controls.
A seventeen hour long water deprivation test was carried out in 17 ADPKD patients (CKD I-IV), 16 non-ADPKD patients (CKD I-IV), and 18 healthy controls. Urine was collected in 4 consecutive periods during water deprivation (12 h, 1 h, 2 h and 2 h, respectively) and analyzed for osmolality (u-Osm), output (UO), fractional excretion of sodium (FE), aquaporin2 (u-AQP2) and ENaC (u-ENaC). Blood samples were drawn trice (after 13-, 15-, and 17 h after water deprivation) for analyses of osmolality (p-Osm), vasopressin (p-AVP), and aldosterone (p-Aldo).
U-Osm was significantly lower and FE significantly higher in both ADPKD patients and non-ADPKD patients compared to healthy controls during the last three periods of water deprivation. During the same periods, UO was higher and secretion rates of u-AQP2 and u-ENaC were lower and at the same level in the two groups of patients compared to controls. P-AVP and p-Osm did not differ significantly between the three groups. P-Aldo was higher in both groups of patients than in controls.
Urine concentration ability was reduced to the same extent in patients with ADPKD and other chronic kidney diseases with the same level of renal function compared to healthy controls. The lower urine excretion of AQP2 and ENaC suggests that the underlying mechanism may be a reduced tubular response to vasopressin and aldosterone.
Current Controlled Trial NCT04363554 , date of registration: 20.08.2017.
尿液的浓缩主要通过肾脏主细胞顶膜上的血管加压素依赖的水通道蛋白-2（AQP2）进行调节。目前尚不清楚多囊肾病（ADPKD）患者的尿液浓缩能力是否与其他肾功能受损程度相似（非 ADPKD 患者）的患者不同。本病例对照研究的目的是测量 ADPKD 患者与非 ADPKD 患者和健康对照组的尿液浓缩能力。
对 17 例 ADPKD 患者（CKD I-IV 期）、16 例非 ADPKD 患者（CKD I-IV 期）和 18 例健康对照者进行 17 小时的限水试验。在限水期间（分别为 12h、1h、2h 和 2h）连续收集 4 段尿液，并分析渗透压（u-Osm）、尿量（UO）、钠排泄分数（FE）、水通道蛋白 2（u-AQP2）和上皮钠通道（u-ENaC）。在限水后 13、15 和 17 小时采血 3 次，分析渗透压（p-Osm）、血管加压素（p-AVP）和醛固酮（p-Aldo）。
与健康对照组相比，在最后三个限水期，ADPKD 患者和非 ADPKD 患者的 u-Osm 显著降低，FE 显著升高。在同一时期，两组患者的 UO 较高，u-AQP2 和 u-ENaC 的分泌率较低且与对照组相同。三组间 p-AVP 和 p-Osm 无显著差异。两组患者的 p-Aldo 均高于对照组。
与健康对照组相比，ADPKD 患者和肾功能相同的其他慢性肾脏病患者的尿液浓缩能力均有不同程度的降低。AQP2 和 ENaC 的尿排泄量较低提示，其潜在机制可能是对血管加压素和醛固酮的肾小管反应降低。
当前对照试验 NCT04363554，注册日期：2017 年 8 月 20 日。
