摘要
第一部分慢性肾脏病患者尿血管紧张素原检测的意义及其相关因素背景
肾内血管紧张素原主要分布于近端肾小管。近端肾小管内的血管紧张素原形成后被分泌入肾小管管腔,并在肾素、血管紧张素转换酶的作用下进一步形成血管紧张素Ⅱ,是肾内血管紧张素Ⅱ的主要来源。血管紧张素原分子量大,循环血管紧张素原不能通过肾小球滤过屏障,所以尿血管紧张素原主要来源于近端肾小管,而与循环血管紧张素原无关。已有大量动物试验提示尿血管紧张素原水平与肾内血管紧张素原、血管紧张素Ⅱ含量呈正相关,尿血管紧张素原可能是肾内肾素—血管紧张素系统(renin-angiotensin system, RAS)活性的指标。所以,本研究以慢性肾脏病入手,旨在分析慢性肾脏病患者尿血管紧张素原的相关因素。方法
2009.4～2009.5在复旦大学附属中山医院肾内科病房住院治疗的临床资料完整的74例慢性肾脏病患者,取得患者知情同意,并排除最近2个月内曾服用血管紧张素转换酶抑制剂和/或血管紧张素Ⅱ受体阻断剂的患者。记录患者的性别、年龄、身高、体重、住院期间血压、尿常规、肾功能、电解质、24小时尿蛋白、尿钠。并于清晨、卧位采集肘静脉血8ml分离血浆和血清,同时收集新鲜晨尿10ml分离上清液,利用放射免疫法和ELISA方法测定血、尿肾素—血管紧张素系统各组分的浓度。评价尿血管紧张素原与临床指标的相关性。结果
74例慢性肾脏病患者尿血管紧张素原为209.28±133.99 ng/(mg Cr)[49.48-724.81 ng/(mg Cr)],估算肾小球滤过率(estimated glomerular filtration rate, eGFR)为51.34±30.26 ml/min/1.73m2(3.99-163.94 ml/min/1.73m2),尿血管紧张素Ⅱ为134.69±95.09 pg/(mg Cr)[45.73-580.06 pg/(mg Cr)],尿Ⅳ型胶原为672.91±989.10 ng/(mg Cr)[37.53-6269.48 ng/(mg Cr)],尿钠为157.73±76.75 mmol/24h (8.00-425.00 mmol/24h)。经Pearson单因素相关分析,尿血管紧张素原与eGFR呈负相关(r=-0.56,P<0.01)；尿血管紧张素原与尿血管紧张素Ⅱ呈正相关(r=0.56,p<0.01)；尿血管紧张素原与尿Ⅳ型胶原呈正相关(r=0.41,p<0.01)；尿血管紧张素原与尿钠呈负相关(r=-0.25,P<0.05)。进一步对eGFR、尿血管紧张素Ⅱ、尿Ⅳ型胶原、尿钠进行多元回归分析,发现尿血管紧张素原与eGFR呈负相关(P<0.01),尿血管紧张素原与尿血管紧张素Ⅱ、尿Ⅳ型胶原呈正相关(P<0.01)。尿醛固酮、24小时尿蛋白、血浆肾素活性、血清血管紧张素原、血浆血管紧张素Ⅱ、血清醛固酮、血清钠、血清钾、收缩压、舒张压、年龄、体重指数和性别与尿血管紧张素原无显著相关性。eGFR>60 ml/min/1.73m2组的尿血管紧张素原为143.19±60.10 ng/(mg Cr), eGFR<60 ml/min/1.73m2组的尿血管紧张素原为254.33±151.38 ng/(mg Cr), eGFR<60 ml/min/1.73m2组的尿血管紧张素原水平显著高于eGFR>60 ml/min/1.73m2组(P<0.01)。结论
慢性肾脏病患者尿血管紧张素原与eGFR及尿Ⅳ胶原相关,尿血管紧张素原可能是反映慢性肾脏病中肾脏损伤尤其是慢性损伤程度的指标。
第二部分尿血管紧张素原与肾脏局部肾素—血管紧张素系统活性的关系背景
各种证据提示肾内肾素—血管紧张素系统的过度兴奋是慢性肾脏病发生发展的关键因素。尿血管紧张素Ⅱ不仅来自于肾脏局部形成的血管紧张素Ⅱ,还有部分来自循环血管紧张素Ⅱ,尿血管紧张素Ⅱ并不是反映肾内血管紧张素Ⅱ活性的稳定指标。动物研究结果说明尿血管紧张素原可能与肾内血管紧张素Ⅱ活性相关,是肾内肾素—血管紧张素系统活性的评价指标。但是目前关于尿血管紧张素原与肾内血管紧张素Ⅱ活性关系的数据主要来自啮齿类动物的研究,尚缺乏人类研究。如果得到人类研究结果证实,尿血管紧张素原可能成为血压、蛋白尿、肾小球滤过率以外,评价慢性肾脏病患者肾内RAS活化或阻断程度的重要工具。本研究旨在分析慢性肾脏病患者尿血管紧张素原与肾内血管紧张素Ⅱ活性的关系。
方法
2009.4～2009.5在复旦大学附属中山医院肾内科病房行肾脏活组织检查的临床和病理资料完整的73例慢性肾脏病患者,取得患者知情同意,并排除最近2个月内曾服用血管紧张素转换酶抑制剂和／或血管紧张素Ⅱ受体阻断剂的患者。收集新鲜晨尿10ml分离上清液,利用ELISA方法测定尿血管紧张素原。同时利用免疫组织化学的方法评价患者肾内肾素—血管紧张素系统各组分的表达,评价尿血管紧张素原与肾内肾素—血管紧张素系统各组分表达的相关性。
结果
73例慢性肾脏病患者尿血管紧张素原为210.24±134.65 ng/(mg Cr)[49.48-724.81 ng/(mg Cr)],肾内血管紧张素原免疫组化染色面积为39.15±19.35%(5.00-88.00%),肾内血管紧张素Ⅱ免疫组化染色面积为31.85±19.75%(3.00-81.00%),肾内血管紧张素Ⅱ1型受体免疫组化染色面积为44.50±16.14%(8.00-88.00%)。经Pearson单因素相关分析,尿血管紧张素原与肾内血管紧张素原免疫组化染色面积呈正相关(r=0.45,P<0.01)；尿血管紧张素原与肾内血管紧张素Ⅱ免疫组化染色面积呈正相关(r=0.52,P<0.01)；尿血管紧张素原与肾内血管紧张素Ⅱ1型受体免疫组化染色面积呈正相关(r=0.28,P<0.05)。尿血管紧张素原与肾内肾素、血管紧张素Ⅱ2型受体免疫组化染色面积无显著相关性。
结论
尿血管紧张素原能较好地反映慢性肾脏病患者肾脏局部的血管紧张素Ⅱ活性,可做为肾内RAS活性的无创评价指标。
第三部分血管紧张素Ⅱ受体阻断剂对肾脏局部肾素—血管紧张素系统表达的影响
背景
大量证据表明肾脏存在血管紧张素Ⅱ1型受体高表达,所以肾脏是肾素—血管紧张素系统的主要靶器官。但目前仍缺乏关于血管紧张素Ⅱ受体阻断剂(angiotensinⅡreceptor blocker, ARB)对人体肾内肾素—血管紧张素系统整体活性影响的直接数据,也缺乏数据证明ARB治疗后尿血管紧张素原是否仍能有效反映肾内肾素—血管紧张素系统活性。本研究旨在分析ARB治疗后尿血管紧张素原是否仍能有效反映肾内RAS的活性,并进一步观察ARB治疗对慢性肾脏病患者肾内RAS表达的影响。
方法
2009.4～2009.5在复旦大学附属中山医院肾内科行肾脏活组织检查并曾经服用过2周以上ARB(剂量、种类不限)的17例慢性肾脏病患者(ARB治疗组),取得患者知情同意,并排除最近2个月内曾服用血管紧张素转换酶抑制剂的患者。第一部分中的研究对象根据eGFR、24小时尿蛋白、尿钠、血压等情况与之进行1：1配对(空白对照组),共配成17对。记录患者性别、年龄、身高、体重、住院期间血压、尿常规、肾功能、电解质、24小时尿蛋白、尿钠。于清晨、卧位采集肘静脉血8ml分离血浆和血清,同时收集新鲜晨尿10ml分离上清液,利用放射免疫法和ELISA方法测定血、尿肾素—血管紧张素系统各组分的浓度。并利用免疫组织化学的方法评价患者肾内肾素—血管紧张素系统各组分的表达。评价ARB治疗组尿血管紧张素原与肾内肾素—血管紧张素系统各组分表达的相关性以及两组间血、尿和肾组织肾素—血管紧张素系统活性的差异。
结果
ARB治疗组患者尿血管紧张素原为219.17±211.54 ng/(mg Cr)[17.27-700.47 ng/(mg Cr)],肾内血管紧张素原免疫组化染色面积为34.76±15.64% (10.00-65.00%),肾内血管紧张素Ⅱ免疫组化染色面积为33.76±18.82% (10.00-70.00%),肾内血管紧张素Ⅱ1型受体免疫组化染色面积为43.65±26.17%(15.00-92.00%)。经Pearson单因素相关分析,尿血管紧张素原与肾内血管紧张素原免疫组化染色面积呈正相关(r=0.54, P<0.05);尿血管紧张素原与肾内血管紧张素Ⅱ免疫组化染色面积呈正相关(r=0.50, P<0.05);尿血管紧张素原与肾内血管紧张素Ⅱ1型受体免疫组化染色面积呈正相关(r=0.58,P<0.05)。ARB治疗组患者尿血管紧张素原与肾内肾素、血管紧张素Ⅱ2型受体免疫组化染色面积无显著相关性。ARB治疗组血浆血管紧张素Ⅱ63.09±15.14 pg/ml,空白对照组血浆血管紧张素Ⅱ53.66±8.33 pg/ml, ARB治疗组血浆血管紧张素Ⅱ显著高于空白对照组(P<0.05); ARB治疗组肾内肾素免疫组化染色面积为48.65±19.58%,空白对照组肾内肾素免疫组化染色面积为30.29±24.98%, ARB治疗组肾内肾素免疫组化染色面积显著高于空白对照组(P<0.05)。ARB治疗组肾内血管紧张素原、血管紧张素Ⅱ和血管紧张素Ⅱ1型受体免疫组化染色面积略低于空白对照组,但无统计学意义。两组在收缩压、舒张压、eGFR、24小时尿蛋白、尿钠、血浆肾素活性、血清血管紧张素原、血清醛固酮、尿血管紧张素原、尿血管紧张素Ⅱ、尿醛固酮和肾内血管紧张素Ⅱ2型受体免疫组化染色面积等方面无显著性差异。
结论
血管紧张素Ⅱ受体阻断剂治疗后,慢性肾脏病患者尿血管紧张素原仍能较好地反映肾脏局部的血管紧张素Ⅱ活性。血管紧张素Ⅱ受体阻断剂治疗对循环和肾脏局部肾素—血管紧张素系统活性的影响不同,可使得循环血管紧张素Ⅱ升高,并可能抑制肾脏局部血管紧张素Ⅱ的表达。
第四部分原发性IgA肾病患者肾脏局部肾素—血管紧张素系统表达及其与临床病理损伤的关系
背景
目前关于人类肾脏,尤其是人类肾脏疾病中肾素—血管紧张素系统各组分的表达及其相互调节的数据很少,大部分关于肾素—血管紧张素系统组分表达和调节的数据来源于动物。有必要对人类肾脏和肾脏疾病中的这些数据进行全面评价,因为循环肾素—血管紧张素系统组分的改变并不能直接反映肾脏局部肾素—血管紧张素系统的表达和调节,而且肾内RAS活性的效应并不能通过单一某种组分的测定得到精确评价,所以必须对RAS各组分的肾内表达进行同时评价。本研究旨在全面分析原发性IgA肾病患者肾脏局部肾素—血管紧张素系统各组分的表达及其相互调节,同时分析肾内血管紧张素Ⅱ表达与临床病理损伤指标间的关系。
方法
2009.1～2009.6在复旦大学附属中山医院肾内科病房行肾脏活组织检查,术后病理证实为原发性IgA肾病的36例患者,取得患者知情同意,并排除曾服用糖皮质激素、免疫抑制剂、血管紧张素转换酶抑制剂和/或血管紧张素Ⅱ受体阻断剂的患者。记录研究对象性别、年龄、身高、体重、住院期间血压、尿常规、肾功能、电解质、24小时尿蛋白、尿钠。。肾小球、肾小管及血管的各项病理参数的半定量积分采用Katafuchi评分标准,并利用免疫组织化学的方法评价患者肾内肾素—血管紧张素系统各组分的表达。分析原发性IgA肾病患者肾脏局部肾素—血管紧张素系统各组分表达之间的相关性以及肾内血管紧张素Ⅱ表达与血压、GFR、24小时尿蛋白和肾脏病理评分之间的相关性。
结果
36例IgA肾病患者肾内肾素、血管紧张素原和血管紧张素Ⅱ免疫组化染色面积分别为26.86±13.66%(7-55%),38.34±9.71%(12-57%)和32.73±14.74%(6-70%)。经Pearson单因素相关分析,肾内肾素与血管紧张素Ⅱ表达呈正相关(r=0.43, P<0.01),肾内血管紧张素原与血管紧张素Ⅱ表达呈正相关(r= 0.34, P<0.05)。eGFR平均值为55.92±22.87 ml/min/1.73m2(6.62-92.49 ml/min/1.73 m2),肾内血管紧张素Ⅱ免疫组化染色面积与eGFR呈负相关(r=-0.61,P<0.01)；慢性化积分为3.06±2.60(0-10),肾内血管紧张素Ⅱ免疫组化染色面积与慢性化积分呈正相关(p=0.39,P<0.05)。
结论
IgA肾病患者肾内血管紧张素Ⅱ表达与肾内肾素、血管紧张素原表达相关,并且肾内血管紧张素Ⅱ活性与肾脏纤维化过程相关。
PartⅠThe significance and clinical factors related to the level of urinary angiotensinogen in chronic kidney disease patients
Background
Several authors have demonstrated that intrarenal angiotensinogen is mainly local-ized to proximal tubule. The angiotensinogen produced in proximal tubule cells seems to be secreted directly into the tubular lumen and converted to angiotensinⅡ(AngⅡ) by renin and angiotensin converting enzyme (ACE). Tubular angiotensinogen has been proposed to be the major intrarenal source for AngⅡ. Because of its molecular size, it seems unlikely that much of the plasma angiotensinogen filters across the glomerular membrane, further supporting the concept that urinary angiotensinogen is mainly secreted by proximal tubule cells, having nothing to with general angiotensinogen. Many animal experiments have demonstrated that there is positive correlation between urinary angiotensinogen and intrarenal angiotensinogen and AngⅡcontent. These data also suggest the potential of urinary angiotensinogen as a marker of intrarenal RAS activity. This study was designed to analyze the clinical factors related to the level of urinary angiotensinogen in chronic kidney disease (CKD) patients.
Methods
Seventy-four CKD patients who were hospitalized in Shanghai Zhongshan Hospital between April 2009 and May 2009, had not received angiotensin converting enzyme inhibitor(ACEI) or angiotensinⅡreceptor blocker(ARB) during last two months, and gave informed consent were included in the study. We recorded gender, age, height, body weight, blood pressure, urine routine, renal function, serum electrolytes, urinary protein of 24 hours and urinary sodium. Blood samples were collected at bed rest early in the morning and fresh urine samples were collected after waking up. We measured plasma renin activity, plasma and urinary angiotensinogen, AngⅡand aldosterone by RIA or ELISA in order to determine the clinical factors related to the level of urinary angiotensinogen.
Results
Average urinary angiotensinogen in 74 chronic kidney disease patients was 209.28±33.99 ng/(mg Cr)[49.48-724.81 ng/(mg Cr)]. Average estimated glomerular filtration rate(eGFR) was 51.34±30.26 ml/min/1.73m2(3.99-163.94 ml/min/1.73m2) and there was negative correlation between urinary angiotensinogen and eGFR(r= -0.56, P<0.01). Average urinary AngⅡwas 134.69±95.09 pg/(mg Cr)[45.73-580.06 pg/(mg Cr)] and there was positive correlation between urinary angiotensinogen and urinary AngⅡ(r= 0.56, P<0.01). Average urinary typeⅣcollagen was 672.91±989.10 ng/(mg Cr)[37.53-6269.48 ng/(mg Cr)] and there was positive correlation between urinary angiotensinogen and urinary type IV collagen(r=0.41, P<0.01). Average urinary soduim was 157.73±76.75 mmol/24h(8.00-425.00 mmol/24h) and there was negative correlation between urinary angiotensinogen and urinary sodium(r=-0.25, P<0.05). Multiple regression analysis indicated that low eGFR(P<0.01), high urinary AngⅡ(P<0.01) and high urinary typeⅣcollagen (P<0.01 correlated significantly with high urinary angiotensinogen. Urinary angiotensinogen did not correlate significantly with plasma renin activity, serum angiotensinogen, plasma AngⅡ, serum and urinary aldosterone, urinary protein of 24 hours, serum sodium, serum potassium, blood pressure, BMI, or gender. Average urinary angiotensinogen in patients whose eGFR were lower than 60 ml/min/1.73m2 was higher than that in patients whose eGFR were higher than 60 ml/min/1.73m2 [254.33±151.38 ng/(mg Cr) vs.143.19±60.10 ng/(mg Cr), P<0.01].
Conclusion
There is negative correlation between urinary angiotensinogen and eGFR and there is positive correlation between urinary angiotensinogen and urinary type IV collagen in chronic kidney disease patients.Urinary angiotensinogen maybe a marker of kidney injury, especially chronic kidney injury in chronic kidney disease.
PartⅡThe relationship between urinary angiotensinogen and intrarenal renin-angiotensin system activity
Background
The crucial role of over-activation of intrarenal renin-angiotensin system (RAS) in the development and progression of chronic kidney disease is widely recognized. Urinary AngⅡincludes focal AngⅡformed intrarenally and part of general AngⅡfiltering across the glomerular membrane. Urinary AngⅡis not a stable marker of intrarenal AngⅡactivity. Many animal experiments have demonstrated that there is positive correlation between urinary angiotensinogen and intrarenal AngⅡactivity and these data also suggest the potential of urinary angiotensinogen as a marker of intrarenal RAS activity. However, most data about urinary angiotensinogen and intrarenal AngⅡactivity derive from animal studies. Studies in humans are lacking, but if results from the preliminary studies are confirmed, urinary angiotensinogen might constitute an invaluable tool for measuring the degree of RAS activation or blockade in individuals with chronic kidney disease, beyond blood pressure, proteinuria and eGFR. This study was designed to analyze the relationship between urinary angiotensinogen and intrarenal AngⅡactivity.
Methods
Senenty-there CKD patients who were hospitalized in Shanghai Zhongshan Hospital between April 2009 and May 2009, had not received ACEI or ARB during last two months, and gave informed consent were included in the study. Fresh urine samples were collected after waking up and we measured urinary angiotensinogen by ELISA. Experssion of all the components of intrarenal RAS was assessed by immunohistochemistry staining (IHCS) in order to determine the relationship between urinary angiotensinogen and expression of all the components of intrarenal renin-angiotensin system.
Results
Average urinary angiotensinogen in 73 chronic kidney disease patients was 210.24±134.65 ng/(mg Cr)[49.48-724.81 ng/(mg Cr)]. Positive IHCS area of intrarenal angiotensinogen was 39.15±19.35%(5.00-88.00%) and there was positive correlation between urinary angiotensinogen and positive IHCS area of intrarenal angiotensinogen (P<0.01). Positive IHCS area of intrarenal AngⅡwas 31.85±19.75% (3.00-81.00%) and there was positive correlation between urinary angiotensinogen and positive IHCS area of intrarenal AngⅡ(P<0.01). Positive IHCS area of intrarenal angiotensinⅡtype 1 receptor (AT1R) was 44.50±16.14%(8.00-88.00%) and there was positive correlation between urinary angiotensinogen and positive IHCS area of intrarenal AT1R (P<0.05). Urinary angiotensinogen did not correlate significantly with positive IHCS area of intrarenal renin and angiotensinⅡtype 2 receptor(AT2R).
Conclusion
Urinary angiotensinogen can reflect intrarenal agiotensinⅡactivity in chronic kidney disease patients and constitutes an invasive marker of intrarenal RAS activity.
PartⅢThe effect of angiotensinⅡreceptor blocker on expression of intrarenal renin-angiotensin system
Background
The kidney is a major target for the RAS, as evidenced by the robust renal expression of the AT1R. Data about the effect of ARB on intrarenal RAS activity is still lacking and there is no evidence to support that urinary angiotensinogen is still a marker of intrarenal RAS activity after the treatment of ARB. This study was designed to analyze whether urinary angiotensinogen is still a marker of intrarenal RAS activity after the treatment of ARB and observe the effect of ARB on expression of intrarenal renin-angiotensin system.
Methods
Senenteen CKD patients who were hospitalized in Shanghai Zhongshan Hospital between April 2009 and May 2009, had received ARB for at least two weeks, had not received ACEI during last 2 months, and gave informed consent were included in the study (ARB group). They were matched pair with patients in partⅠaccording to eGFR, urinary protein of 24 hours, urinary sodium and blood pressure (control group). We recorded gender, age, height, body weight, blood pressure, urine routine, renal function, serum electrolytes, urinary protein of 24 hours and urinary sodium. Blood samples were collected at bed rest early in the morning and fresh urine samples were collected after waking up. We measured plasma renin activity, plasma and urinary angiotensinogen, AngⅡand aldosterone by RIA or ELISA and assess experssion of all the components of intrarenal RAS by immunohistochemistry staining in order to determine the relationship between urinary angiotensinogen and expression of all the componenets of intrarenal renin-angiotensin system in ARB group and the difference of general and focal renin-angiotensin system activity between two groups.
Results
Average urinary angiotensinogen in ARB group was 219.17±211.54 ng/(mg Cr) [17.27-700.47 ng/(mg Cr)]. Positive IHCS area of intrarenal angiotensinogen was 34.76±15.64%(10.00-65.00%) and there was positive correlation between urinary angiotensinogen and positive IHCS area of intrarenal angiotensinogen (P<0.05). Positive IHCS area of intrarenal AngⅡwas 33.76±18.82%(10.00-70.00%) and there was positive correlation between urinary angiotensinogen and positive IHCS area of intrarenal AngⅡ(P<0.05). Positive IHCS area of AT1R was 43.65±26.17% (15.00-92.00%) and there was positive correlation between urinary angiotensinogen and positive IHCS area of intrarenal ATIR (P<0.05). Urinary angiotensinogen did not correlate significantly with positive IHCS area of intrarenal renin and AT2R. Average plasma AngⅡin ARB group was significantly higher than that in control group (63.09±15.14 pg/ml vs.53.66±8.33 pg/ml, P<0.05). Positive IHCS area of intrarenal renin in ARB group was significantly higher than that in control group (48.65±19.58% vs.30.29±24.98%, P<0.05). Positive IHCS area of intrarenal angio-tensinogen, AngⅡand ATIR in ARB group was lower than those in control group, but the difference had no statistical meaning. There was no difference between two groups on eGFR, urinary protein of 24 hours, blood pressure, urinary sodium, plasma renin activity, serum and urinary angiotensinogen, urinary Angll, serum and urinary al-dosterone, or positive IHCS area of intrarenal AT2R.
Conclusion
Urinary angiotensinogen still can reflect intrarenal angiotensinⅡactivity in chronic kidney disease patients treated by ARB. ARB has different influence on the activity of general and intrarenal RAS. ARB can elevate general angiotensinⅡand probably can inhibit the expression of intrarenal angiotensinⅡ.
PartⅣExpression of intrarenal renin-angiotensin system and its relationship with clinical-pathological injury in primary IgA nephropathy patients
Background
Little information is available about the RAS expression and regulation in the human kidney and particularly in kidney diseases and data on the RAS expression and regulation were mostly obtained in animals.These data in humans and in diseased kidneys would be worthwhile being evaluated because changes in general RAS do not closely reflect local expression and regulation of intrarenal RAS. On the contrary, the simultaneous assessment of the expression and regulation of all components of intrarenal RAS is necessary for evaluation of the net effect of the intrarenal RAS activity. Indeed, the effect of RAS activity on the kidney can not be accurately assessed by the measurement of one component alone. This study was designed to analyze expression and regulation of all the components of intrarenal RAS and the relationship between intrarenal AngⅡexpression and clinical-pathological injury index in primary IgA nephropathy patients.
Methods
Thirty-six biopsy-proved IgA nephropathy patients who were hospitalized in Shanghai Zhongshan Hospital between January 2009 and June 2009, had not received ACEI, ARB, glucocorticoids or immunosuppressive agents, and gave informed consent were included in the study. We recorded gender, age, height, body weight, blood pressure, urine routine, renal function, serum electrolytes, urinary protein of 24 hours and urinary sodium. We assessed pathological injury by semiquantitative Katafuchi score and assessed intrarenal experssion of all the components of the intrerenal RAS by immunohistochemistry staining. We assessed expression and regulation of all the components of intrarenal RAS and the relationship between intrarenal Ang II activity and clinical-pathological injury index in primary IgA nephropathy patients.
Results
Positive IHCS area of intrarenal renin, angiotensinogen and AngⅡwere 26.86±13.66%(7-55%),38.34±9.71%(12-57%) and 32.73±14.74%(6-70%), respectively. There were positive correlation between positive IHCS area of intrarenal renin and positive IHCS area of intrarenal Ang II (P<0.01), positive IHCS area of intrarenal angiotensiongen and positive IHCS area of intrarenal Ang II (P<0.05). Average eGFR in 36 IgA nephropathy patients was 55.92±22.87 ml/min/1.73m2(6.62-92.49 ml/min/1.73m) and there was negative correlation between positive IHCS area of intrarenal AngⅡand eGFR(P<0.01). Average pathological chronicity index in 36 IgA nephropathy patients was 3.06±2.60 (0-10) and there was positive correlation between positive IHCS area of intrarenal AngⅡand pathological chronicity index (P<0.05).
Conclusion
Expression of intrarenal AngⅡcorrelates positively with expression of intrarenal renin and angiotensinogen in IgA nephropathy. Intrarenal AngⅡactivity plays an important role in kidney fibrosis in IgA nephropathy.
引文
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