The Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.
Clin Exp Nephrol. 2022 Aug;26(8):788-796. doi: 10.1007/s10157-022-02220-1. Epub 2022 May 3.
In the collecting ducts of the kidney, arginine vasopressin (AVP), cyclic adenosine monophosphate (cAMP), and aquaporin 2 (AQP2) play a pivotal role in maintaining fluid volume and serum osmolality in humans. However, their association among those with chronic kidney disease (CKD) remains uncertain.
We prospectively included the out-patients with CKD and measured osmolality-related biomarkers including plasma AVP, urine cAMP, urine AQP2, and urine osmolality levels. Association among these parameters at each CKD stage was investigated.
A total of 121 patients were included (median age 71 years old [61-78], 89 men, estimated glomerular filtration ratio 28.6 [16.4-45.3] mL/min/1.73 m). Serum osmolality increased as CKD progression, accompanying incremental plasma AVP levels, whereas urine cAMP, urine AQP2, and urine osmolality decreased as CKD progression. At advanced CKD stage, urine cAMP remained low irrespective of the AVP stimulation, whereas urine cAMP levels varied according to the levels of plasma AVP at less advanced CKD stage. The associations between urine cAMP and urine AQP2 and between urine AQP2 and urine osmolality remained preserved irrespective of the CKD stages.
Vasopressin type-2 receptor seems to be particularly impaired in patients with advanced CKD, whereas the signal cascade of the downstream of vasopressin type-2 receptor is relatively preserved. Urine cAMP might be a promising marker to estimate the residual function of the collecting duct.
在肾脏的集合管中，精氨酸加压素（AVP）、环磷酸腺苷（cAMP）和水通道蛋白 2（AQP2）在维持人体液体量和血清渗透压方面发挥着关键作用。然而，它们在慢性肾脏病（CKD）患者中的相关性尚不确定。
我们前瞻性地纳入了 CKD 门诊患者，并测量了渗透压相关生物标志物，包括血浆 AVP、尿 cAMP、尿 AQP2 和尿渗透压水平。研究了这些参数在每个 CKD 阶段之间的相关性。
共纳入 121 例患者（中位年龄 71 岁[61-78]，89 名男性，估算肾小球滤过率 28.6[16.4-45.3]mL/min/1.73m2）。随着 CKD 的进展，血清渗透压增加，伴随血浆 AVP 水平的升高，而尿 cAMP、尿 AQP2 和尿渗透压随着 CKD 的进展而降低。在晚期 CKD 阶段，尽管存在 AVP 刺激，尿 cAMP 仍保持低水平，而尿 cAMP 水平在较不晚期 CKD 阶段则根据血浆 AVP 水平的变化而变化。尿 cAMP 与尿 AQP2 之间以及尿 AQP2 与尿渗透压之间的相关性在 CKD 各阶段均保持不变。
血管加压素 2 型受体在晚期 CKD 患者中似乎受到特别损害，而血管加压素 2 型受体下游的信号级联反应则相对保留。尿 cAMP 可能是一种有前途的评估集合管残余功能的标志物。
