Mostar University Hospital, Mostar, Bosnia and Herzegovina.
J Clin Lab Anal. 2009;23(6):347-56. doi: 10.1002/jcla.20324.
The complex pathogenesis of chronic renal disease (CRD) depends on endothelin (ET) axis (ETs and ET receptors) and nitric oxide (NO) because of their vasoactive effects and their role in general modulation of vascular homeostasis. Various renal cells synthesize ETs and NO that play a significant role in renal hemodynamics as well as in water and salt excretion via urine. ET-1 is a strong vasoconstrictor. Besides its vasoactive effects, ET-1 modulates mitosis and apoptosis in a cell type-dependent manner, and may play an important role in CRD pathogenesis. The aims of this study were to emphasize the role and interactions of ET-1, Big ET-1, and NO in CRD. Concentrations of these vasoactive molecules were measured in plasma/serum and/or urine of 57 patients with diabetic nephropathy (subgroup 1), arterial hypertension (subgroup 2) or CRD with chronic renal insufficiency (subgroup 3), and in healthy control subjects (n=18). In comparison with control group, urine concentration of Big ET-1 was significantly increased (13.13 pmol/L vs. 11.34 pmol/L; P<0.001) in CRD patients, whereas plasma and urine concentrations of ET-1 did not differ significantly. NO concentrations were also significantly increased in CRD patients (serum, 72.55 micromol/L; P<0.001, and urine 141.74 micromol/L; P<0.05) as compared to control group. Study results indicated that Big ET-1 and NO could be useful diagnostic parameters in CRD for their diagnostic sensitivity and diagnostic specificity (Big ET-1 in urine: 56.1 and 88.9%, and NO in serum: 66.7 and 83.3%, respectively). In addition, Big ET-1 may prove useful in the differential diagnosis of diabetic nephropathy (78.6% diagnostic sensitivity and 88.9% diagnostic specificity).
慢性肾脏病（CRD）的复杂发病机制取决于内皮素（ET）轴（ETs 和 ET 受体）和一氧化氮（NO），因为它们具有血管活性作用，并在血管稳态的一般调节中发挥作用。各种肾细胞合成 ETs 和 NO，它们在肾血流动力学以及通过尿液排泄水和盐方面发挥重要作用。ET-1 是一种强烈的血管收缩剂。除了其血管活性作用外，ET-1 还以细胞类型依赖的方式调节有丝分裂和细胞凋亡，并且可能在 CRD 发病机制中发挥重要作用。本研究旨在强调 ET-1、Big ET-1 和 NO 在 CRD 中的作用和相互作用。在 57 例糖尿病肾病（亚组 1）、动脉高血压（亚组 2）或伴有慢性肾功能不全的 CRD（亚组 3）患者的血浆/血清和/或尿液中以及 18 例健康对照者（n=18）中测量这些血管活性分子的浓度。与对照组相比，CRD 患者尿液中的 Big ET-1 浓度显著升高（13.13 pmol/L 比 11.34 pmol/L；P<0.001），而血浆和尿液中的 ET-1 浓度无显著差异。CRD 患者的 NO 浓度也显著升高（血清 72.55 微摩尔/升；P<0.001，尿液 141.74 微摩尔/升；P<0.05）。研究结果表明，Big ET-1 和 NO 可作为 CRD 的有用诊断参数，因为它们具有诊断敏感性和诊断特异性（尿液中的 Big ET-1：56.1%和 88.9%，血清中的 NO：66.7%和 83.3%）。此外，Big ET-1 可能有助于糖尿病肾病的鉴别诊断（诊断敏感性 78.6%，诊断特异性 88.9%）。
