Division of Nephrology and Hypertension, Medical School Hannover, Hannover, Germany.
Nephrol Dial Transplant. 2010 Aug;25(8):2571-6. doi: 10.1093/ndt/gfq060. Epub 2010 Feb 22.
Angiopoietin-2 (Ang-2) is an antagonistic ligand of the endothelial-specific Tie2 receptor. Patients on dialysis have markedly elevated Ang-2 levels, and those correlate with their atherosclerotic burden. The aim of the current study was to investigate the relationship between the circulating levels of Ang-2 and renal function throughout all stages of chronic kidney disease (CKD). In addition, we aimed to detect a potential link between the nitric oxide (NO) synthase inhibitor asymmetric dimethylarginine (ADMA) and the Ang-2 levels.
Glomerular filtration rate (GFR) was assessed by the inulin clearance technique ((i)GFR) and compared to serum Ang-2 (immunoluminometric assay) and ADMA levels (liquid chromatography-electrospray tandem mass spectrometry) in 44 untreated non-smokers at the different stages of CKD 1-4. Ang-2 was also measured in 19 patients on dialysis (CKD stage 5). In addition, the Ang-2 and (c)GFR (cystatin C) measurements were taken in 15 healthy individuals before and 72 h after kidney donation.
The median Ang-2 levels steadily increased across the following groups: healthy controls: 0.77 (0.32-1.08) ng/mL; CKD 1: 0.83 (0.67-1.09) ng/mL; CKD 2: 0.93 (0.74-1.15) ng/mL; CKD 3: 1.13 (0.87-1.49) ng/mL; CKD 4: 1.75 (1.23-2.61) ng/mL; and CKD 5: 4.87 (3.22-7.59) ng/mL, respectively (non-parametric ANOVA P < 0.0001). Ang-2 was associated with the degree of CKD as evidenced by an inverse correlation with the (i)GFR (r = -0.509, P < 0.0001) and positive correlations with homocysteine (r = 0.365, P = 0.015) and phosphate (r = 0.53, P < 0.0001). Additionally, Ang-2 correlated with the ADMA levels (r = 0.35, P = 0.01). We detected a close inverse correlation between the mean changes in GFR and circulating Ang-2 at 72 h after kidney donation (r = -0.54, P = 0.03).
Circulating Ang-2, a putative marker and potential mediator of accelerated atherosclerosis, is inversely related to GFR and increases with advanced CKD. The correlation between Ang-2 and ADMA points towards the hypothesis that the ADMA-driven NO deficiency might trigger Ang-2 release and account for the Ang-2 increase in CKD patients.
血管生成素-2（Ang-2）是内皮特异性 Tie2 受体的拮抗配体。透析患者的 Ang-2 水平明显升高，且其水平与动脉粥样硬化负担相关。本研究旨在探讨 Ang-2 水平与慢性肾脏病（CKD）各期肾功能之间的关系。此外，我们旨在检测一氧化氮（NO）合酶抑制剂不对称二甲基精氨酸（ADMA）与 Ang-2 水平之间的潜在联系。
在 44 名未经治疗的非吸烟者中，使用菊粉清除技术（（i）GFR）评估肾小球滤过率（GFR），并比较血清 Ang-2（免疫发光测定法）和 ADMA 水平（液相色谱-电喷雾串联质谱法）。在 19 名透析患者（CKD 5 期）中也测量了 Ang-2。此外，在 15 名健康个体中，在肾捐献前和 72 小时后测量 Ang-2 和（c）GFR（胱抑素 C）。
Ang-2 水平在以下各组中呈稳步升高趋势：健康对照组：0.77（0.32-1.08）ng/mL；CKD 1 期：0.83（0.67-1.09）ng/mL；CKD 2 期：0.93（0.74-1.15）ng/mL；CKD 3 期：1.13（0.87-1.49）ng/mL；CKD 4 期：1.75（1.23-2.61）ng/mL；CKD 5 期：4.87（3.22-7.59）ng/mL（非参数方差分析 P < 0.0001）。Ang-2 与 CKD 的严重程度相关，这一点可通过与（i）GFR 的负相关关系（r = -0.509，P < 0.0001）和与同型半胱氨酸（r = 0.365，P = 0.015）和磷酸盐（r = 0.53，P < 0.0001）的正相关关系得到证明。此外，Ang-2 与 ADMA 水平相关（r = 0.35，P = 0.01）。我们在肾捐献后 72 小时检测到 GFR 和循环 Ang-2 的平均变化之间存在密切的负相关关系（r = -0.54，P = 0.03）。
作为加速动脉粥样硬化的潜在标志物和介质，循环 Ang-2 与 GFR 呈负相关，并随着 CKD 的进展而增加。Ang-2 与 ADMA 之间的相关性表明，ADMA 驱动的 NO 缺乏可能触发 Ang-2 释放，并解释了 CKD 患者中 Ang-2 水平的升高。
