Division of Nephrology, Department of Medicine, Ottawa Hospital Research Institute, Kidney Research Centre, University of Ottawa, Ottawa, Ontario, Canada.
PLoS One. 2012;7(5):e37649. doi: 10.1371/journal.pone.0037649. Epub 2012 May 22.
Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be a renoprotective enzyme, since it converts angiotensin (Ang) II to Ang-(1-7). ACE2 has been detected in urine from patients with chronic kidney disease. We measured urinary ACE2 activity and protein levels in renal transplant patients (age 54 yrs, 65% male, 38% diabetes, n = 100) and healthy controls (age 45 yrs, 26% male, n = 50), and determined factors associated with elevated urinary ACE2 in the patients. Urine from transplant subjects was also assayed for ACE mRNA and protein. No subjects were taking inhibitors of the renin-angiotensin system. Urinary ACE2 levels were significantly higher in transplant patients compared to controls (p = 0.003 for ACE2 activity, and p≤0.001 for ACE2 protein by ELISA or western analysis). Transplant patients with diabetes mellitus had significantly increased urinary ACE2 activity and protein levels compared to non-diabetics (p<0.001), while ACE2 mRNA levels did not differ. Urinary ACE activity and protein were significantly increased in diabetic transplant subjects, while ACE mRNA levels did not differ from non-diabetic subjects. After adjusting for confounding variables, diabetes was significantly associated with urinary ACE2 activity (p = 0.003) and protein levels (p<0.001), while female gender was associated with urinary mRNA levels for both ACE2 and ACE. These data indicate that urinary ACE2 is increased in renal transplant recipients with diabetes, possibly due to increased shedding from tubular cells. Urinary ACE2 could be a marker of renal renin-angiotensin system activation in these patients.
血管紧张素转换酶 2（ACE2）在肾脏中表达，可能是一种肾保护酶，因为它将血管紧张素（Ang）II 转化为 Ang-(1-7)。ACE2 已在慢性肾脏病患者的尿液中检测到。我们测量了 100 例肾移植患者（年龄 54 岁，65%为男性，38%患有糖尿病）和 50 例健康对照者（年龄 45 岁，26%为男性）的尿中 ACE2 活性和蛋白水平，并确定了与患者尿中 ACE2 升高相关的因素。还检测了来自移植患者尿液中的 ACE mRNA 和蛋白。没有患者服用肾素-血管紧张素系统抑制剂。与对照组相比，移植患者的尿 ACE2 水平显著升高（ACE2 活性为 p=0.003，ELISA 或 Western 分析时 ACE2 蛋白为 p≤0.001）。与非糖尿病患者相比，患有糖尿病的移植患者的尿 ACE2 活性和蛋白水平显著升高（p<0.001），而 ACE2 mRNA 水平没有差异。与非糖尿病患者相比，糖尿病移植患者的尿 ACE 活性和蛋白水平显著升高，而 ACE mRNA 水平没有差异。调整混杂因素后，糖尿病与尿 ACE2 活性（p=0.003）和蛋白水平（p<0.001）显著相关，而女性与 ACE2 和 ACE 的尿 mRNA 水平均相关。这些数据表明，糖尿病肾移植受者的尿 ACE2 增加，可能是由于肾小管细胞脱落增加所致。尿 ACE2 可能是这些患者肾脏肾素-血管紧张素系统激活的标志物。
