慢性肾脏病患者尿血管紧张素原与肾脏肾素血管紧张素系统活性的相关性

Correlation between urinary angiotensinogen and intrarenal renin-angiotensin system activityin chronic kidney disease patients

目的探讨慢性肾脏病（CKD）患者尿血管紧张素原（AGT）与肾损伤指标及肾脏局部肾素血管紧张素系统（RAS）活性的关系。方法用放射免疫法和酶联免疫吸附法（ELISA）测定血、尿RAS组分的浓度，并用免疫组织化学方法评价肾内肾素、ACT、血管紧张素Ⅱ（AngⅡ）和血管紧张素Ⅱ受体的表达。分析129例CKD患者尿AGT与临床指标的相关性以及73例行肾组织活检的CKD患者尿AGT与肾脏局部RAS组分表达的相关性。结果129例CKD患者尿AGT（159．08±125．18）μg／g Cr，Scr（113．20±105．05）μmol／L，估算肾小球滤过率（eGFR）（58．52±27．15）ml·min-1·（1．73m2）-1，尿蛋白量（2．03±2．65）g／24h，尿Ang Ⅱ（164．71±139．25）ng／g Cr，尿Ⅳ型胶原（447．60±800．66）μg／g Cr，尿钠（162．17±81．61）mmol／24h。经Pearson单因素相关分析，尿AGT与eGFR（r=-0．55，P〈0．01）、尿钠（r=-0．20，P〈0．05）呈负相关；与Ser（r=0．51，P〈0．01）、24h尿蛋白量（r=0．30，P〈0．01）、尿AngⅡ（r=0．20，P〈0．05）及尿Ⅳ型胶原（r=0．47，P〈0．01）呈正相关。多元回归分析发现尿AGT与eGFR呈负相关（P〈0．01），与Scr（P〈0．01）、24h尿蛋白量（P〈0．05）、尿Ang Ⅱ（P〈0．05）、尿Ⅳ型胶原（P〈0．01）呈正相关。73例CKD患者。肾活检组织中，尿AGT与肾脏AGT（r=0．45，P〈0．01）、Ang1I（r=0．52，P〈0．01）和Ang Ⅱ1型受体（r=0．28，P〈0．05）免疫组化阳性面积呈正相关。结论尿AGT可能是反映CKD肾脏损伤尤其是慢性损伤程度的指标，可作为肾脏局部AngⅡ活性的无创评价指标。

Objective To analyze the correlation of urinary angiotensinogen （AGT） with clinical index of kidney injury and intrarenal renin-angiotensin system （RAS） activity in chronic kidney disease （CKD） patients. Methods Urinary or plasma renin activity, AGT, angiotensin Ⅱ （Ang Ⅱ ）, aldosterone were measured by RIA or ELISA in 129 CKD patients. Expression of intrarenal renin, AGT, Ang Ⅱ and angiotensin Ⅱ receptor was examined by immunohistochemistry staining （IHCS） in 73 CKD patients undergoing renal biopsy. Correlation of urinary AGT with other indexes was performed. Results Average urinary AGT in 129 CKD patients was （159.08±125.18） μg/g Cr, Scr was （113.20±105.05） μmol/L, and urinary AGT was positively correlated with Scr （r=0.51, P〈0.01）. Average estimated glomerular filtration rate （eGFR） was （58.52±27.15） ml·min-1 ·（1.73 m^2）-1, which was negatively correlated with urinary AGT （r=-0.55, P〈0.01）. Average urinary protein was （2.03±2.65） g/24 h, which was positively correlated with urinary AGT （r=0.30, P〈0.01）. Average urinary Ang H was （164.71±139.25） ng/g Cr, which was positively correlated with urinary AGT （r=0.20, P〈0.05）. Average urinary type IV collagen was （447.60± 800.66） μg/g Cr, which was positively correlated with urinary AGT （r=0.47, P〈0.01）. Average urinary soduim was （162.17±81.61） mmol/24 h, which was negatively correlated with urinary AGT （r=-0.20, P〈0.05）. Multiple regression analysis indicated that low eGFR （P〈0.01）, high Ser （P〈 0.01）, high urinary protein （P〈0.05）, high urinary Ang H （P〈0.05） and high urinary type IV collagen （P〈0.01） were significantly correlated with high urinary AGT. In renal tissues of CKD patients, there was positive correlation of urinary AGT with positive IHCS area of AGT （r=0.45, P〈 0.01）, Ang Ⅱ （r =0.52, P〈0.01） and angiotensin II type 1 receptor （r=0.28, P〈0.05）. Conclusions Urinary AGT level may indicate the kidney injury severity, especially in chronic kidney injury, and may be used as a non-invasive marker of intrarenal Ang Ⅱ activity in CKD patients.