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Article(id=1208144411486171698, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208144409313526368, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2022.03.0258, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1632672000000, receivedDateStr=2021-09-27, revisedDate=null, revisedDateStr=null, acceptedDate=1637164800000, acceptedDateStr=2021-11-18, onlineDate=1765973673933, onlineDateStr=2025-12-17, pubDate=1648396800000, pubDateStr=2022-03-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1765973673933, onlineIssueDateStr=2025-12-17, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1765973673933, creator=13701087609, updateTime=1765973673933, updator=13701087609, issue=Issue{id=1208144409313526368, tenantId=1146029695717560320, journalId=1189873630562394117, year='2022', volume='47', issue='3', pageStart='213', pageEnd='319', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1765973673415, creator=13701087609, updateTime=1765974822867, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1208149230531756320, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208144409313526368, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1208149230531756321, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208144409313526368, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=258, endPage=263, ext={EN=ArticleExt(id=1208144411872047669, articleId=1208144411486171698, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Analysis of clinical features of 9 patients with renin secreting tumor and literature review, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To analyze the clinical features of 9 patients with renin secreting tumor and review the related literature in order to improve the understanding, diagnosis and treatment of the disease. Methods The clinical data, diagnosis, treatment, pathological and immunohistochemical profiles of 9 patients with renin secreting tumor admitted in the First Medical Center of Chinese PLA General Hospital from January 2010 to February 2020 were retrospectively analyzed. The literature was searched by retrieving the related database from 2001 to 2020, combined with 142 similar cases collected by searching the database to analyze the clinical features of patients with renin secreting tumor. Results All the 9 patients with an average age of 22.6 years presented with hypertension, and 7 of the 9 with hypokalemia. The plasma renin levels in all the patients were significantly higher than normal range, and the plasma aldosterone levels were above the median normal reference interval. Postoperative pathological examination of all cases confirmed juxtaglomerular cell tumor. Immunohistochemical staining showed that all the tumor cell renin, vimentin and CD34 were positive, some neoplastic cells were positive for smooth muscle actin (SMA) and synaptophysin (Syn), and negative for S-100 protein (S-100) and chromogranin A (CgA). The blood pressure and serum potassium level returned to normal range in all patients after surgery. A total of 142 patients with renin secreting tumor have been reported in China from 2001 to 2020.Hypertension was the initial symptom of all the patients. Hypokalemia occurred in 87 of 142 patients. Plasma renin and aldosterone levels were above the normal range in 93 patients. No recurrence or metastasis occurred in all patients after surgery during follow-up. Conclusions Renin secreting tumor mostly is characterized as benign renal tumor with hypertension, hypokalemia, hyperreninemia and hyperaldosteronism. Surgery is preferred in treatment of this tumor for a good prognosis.

, correspAuthors=Kang Chen, authorNote=null, correspAuthorsNote=
*E-mail:
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目的 分析9例肾素分泌瘤患者的临床特征并进行相关文献复习，以提高对该病的认识及诊疗水平。方法 收集解放军总医院第一医学中心2010年1月－2020年2月收治的9例肾素分泌瘤患者的临床资料、诊治情况、病理和免疫组化染色结果进行回顾性分析。检索2001－2020年的相关数据库，结合文献报道的142例患者分析肾素分泌瘤的临床特点。结果 9例患者平均年龄22.6岁，均表现为高血压，7例为低钾血症。所有患者血浆肾素水平均明显高于正常，醛固酮水平高于正常参考区间中位数。术后病理证实均为肾球旁细胞瘤。免疫组化染色结果显示肿瘤细胞肾素、波形蛋白和CD34均呈阳性，部分肿瘤细胞平滑肌肌动蛋白(SMA)和突触素(Syn)呈阳性，S-100蛋白(S-100)和嗜铬素A(CgA)均呈阴性。术后所有患者血压和血钾水平恢复正常。2001－2020年共报道我国肾素分泌瘤患者142例，首发症状均为高血压，87例为低钾血症，93例血肾素与醛固酮水平增高，随访所有患者均未出现复发及转移情况。结论 肾素分泌瘤多为肾良性肿瘤，临床表现为高血压、低血钾、高肾素、高醛固酮血症的特点，该病可手术治疗，一般预后良好。

, correspAuthors=陈康, authorNote=null, correspAuthorsNote=
陈康，E-mail：
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刘兰荣，医学硕士，主治医师，主要从事内分泌基础与临床方面的研究

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刘兰荣，医学硕士，主治医师，主要从事内分泌基础与临床方面的研究

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J Hypertens, 2015, 33(8): 1709-1715., articleTitle=A case report of reninoma: radiological and pathological features of the tumor and characterization of tumor-derived juxtaglomerular cells in culture, refAbstract=null), Reference(id=1208144421133071336, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, doi=null, pmid=null, pmcid=null, year=2013, volume=44, issue=1, pageStart=47, pageEnd=54, url=null, language=null, rfNumber=[20], rfOrder=22, authorNames=Kuroda N, Maris S, Monzon FA, journalName=Hum Pathol, refType=null, unstructuredReference=Kuroda N, Maris S, Monzon FA, et al. Juxtaglomerular cell tumor: a morphological, immunohistochemical and genetic study of six cases[J]. Hum Pathol, 2013, 44(1): 47-54., articleTitle=Juxtaglomerular cell tumor: a morphological, immunohistochemical and genetic study of six cases, refAbstract=null), Reference(id=1208144421237928942, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, doi=null, pmid=null, pmcid=null, year=2008, volume=39, issue=3, pageStart=459, pageEnd=462, url=null, language=null, rfNumber=[21], rfOrder=23, authorNames=Capovilla M, Couturier J, Molinié V, journalName=Hum Pathol, refType=null, unstructuredReference=Capovilla M, Couturier J, Molinié V, et al. Loss of chromosomes 9 and 11 may be recurrent chromosome imbalances in juxtaglomerular cell tumors[J]. Hum Pathol, 2008, 39(3): 459-462., articleTitle=Loss of chromosomes 9 and 11 may be recurrent chromosome imbalances in juxtaglomerular cell tumors, refAbstract=null)], funds=[Fund(id=1208144418641654654, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, awardId=D141107005314004, language=EN, fundingSource=Science and Technology Project of Beijing(D141107005314004), fundOrder=null, country=null), Fund(id=1208144418759095171, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, awardId=D141107005314004, language=CN, fundingSource=北京市科技计划课题(D141107005314004), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1208144413356831305, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, xref=1, ext=[AuthorCompanyExt(id=1208144413365219914, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, companyId=1208144413356831305, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China), AuthorCompanyExt(id=1208144413377802828, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, companyId=1208144413356831305, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1解放军总医院第一医学中心内分泌科，北京 100853)]), AuthorCompany(id=1208144413520409166, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, xref=2, ext=[AuthorCompanyExt(id=1208144413532992079, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, companyId=1208144413520409166, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2Department of Endocrinology, the People's Hospital of Chengwu County, Heze, Shandong 274200, China), AuthorCompanyExt(id=1208144413549769297, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, companyId=1208144413520409166, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2成武县人民医院内分泌科，山东菏泽 274200)]), AuthorCompany(id=1208144413646238293, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, xref=3, ext=[AuthorCompanyExt(id=1208144413654626902, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, companyId=1208144413646238293, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3Department of Endocrinology, the People's Hospital of Xingtai, Xingtai, Hebei 054000, China), AuthorCompanyExt(id=1208144413692375639, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, companyId=1208144413646238293, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3邢台市人民医院内分泌科，河北邢台 054000)])], figs=[ArticleFig(id=1208144417614050117, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, language=EN, label=Fig.1, caption=Kidney MRI of the patients with renin secreting tumor, figureFileSmall=m3Bc34Wye7xQRDu8p4RxAA==, figureFileBig=S4zTe4KjHLcEdu4k4H/m9Q==, tableContent=null), ArticleFig(id=1208144417765045065, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, language=CN, label=图1, caption=肾素分泌瘤患者肾脏MRI表现

A. MRI平扫显示左肾中下极10 mm×10 mm×7 mm大小、孤立、圆形、边界清楚的肿块，T1加权像呈等强度信号(箭头所示)；B. T2加权像呈低强度信号(箭头所示)；C. MRI动态增强显示皮质期无明显强化(箭头所示)；D. 髓质期轻度强化(箭头所示)

, figureFileSmall=m3Bc34Wye7xQRDu8p4RxAA==, figureFileBig=S4zTe4KjHLcEdu4k4H/m9Q==, tableContent=null), ArticleFig(id=1208144417978954581, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, language=EN, label=Fig.2, caption=Pathology and immunohistochemical staining of the patients with renin secreting tumor, figureFileSmall=4W5eG4MMWz7LNF2/qlzQug==, figureFileBig=4LYC+8CUqCtKdie/vhyzBg==, tableContent=null), ArticleFig(id=1208144418041869145, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, language=CN, label=图2, caption=肾素分泌瘤患者肾标本病理和免疫组化染色结果

A. 手术切除标本：肿物包膜完整，与周围肾组织分界清楚，切面灰白色、实性、质中；B. 镜下肿瘤细胞呈圆形或多边形，边缘清晰，大小均匀，呈巢状排列，胞质呈嗜酸性(HE，×100)；C. 肿瘤细胞胞质肾素呈阳性(SP，×40)；D. 电镜下显示肿瘤细胞内有菱形晶体原颗粒(×10 000)；E. 肿瘤细胞胞质CD34呈阳性(SP，×100)；F. 肿瘤细胞胞质波形蛋白呈阳性(SP，×200)

, figureFileSmall=4W5eG4MMWz7LNF2/qlzQug==, figureFileBig=4LYC+8CUqCtKdie/vhyzBg==, tableContent=null), ArticleFig(id=1208144418134143838, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, language=EN, label=Tab.1, caption=

Baseline clinical data of 9 patients with renin secreting tumor

, figureFileSmall=null, figureFileBig=null, tableContent=
项目患者编号
12345678*9*
性别女男女男女男男男男
年龄(岁)223017282723181424
高血压病程(月)1210.58414812224
最高血压(mmHg)210/150210/125190/140240/140201/147180/120220/110190/140200/110
降压药物ABCCDBCDACABCDACDD
治疗后血压(mmHg)150/100170/100120/70240/160130/90140/100120/80140/100180/130
最低血钾(mmol/L)2.932.723.932.352.502.514.002.501.90
尿钾(mmol/24 h)126.9539.22–33.3548.95––46.8889.28
尿醛固酮#(μg/24 h)25.725.312.186.339.69.4–25.1–
尿钠(mmol/24 h)51.4548.6658.2266.5662.7346.7346.2873.759.22
肿瘤直径(cm)3.02.02.14.52.23.33.01.04.5
随访时间(月)11680887189645964
术后血压(mmHg)120/73120/80130/80160/120115/80120/70130/80120/70130/80
术后血钾(mmol/L)3.503.533.803.813.624.094.083.703.73
), ArticleFig(id=1208144418251584360, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, language=CN, label=表1, caption=

9例肾素分泌瘤患者的基本临床资料

, figureFileSmall=null, figureFileBig=null, tableContent=
项目患者编号
12345678*9*
性别女男女男女男男男男
年龄(岁)223017282723181424
高血压病程(月)1210.58414812224
最高血压(mmHg)210/150210/125190/140240/140201/147180/120220/110190/140200/110
降压药物ABCCDBCDACABCDACDD
治疗后血压(mmHg)150/100170/100120/70240/160130/90140/100120/80140/100180/130
最低血钾(mmol/L)2.932.723.932.352.502.514.002.501.90
尿钾(mmol/24 h)126.9539.22–33.3548.95––46.8889.28
尿醛固酮#(μg/24 h)25.725.312.186.339.69.4–25.1–
尿钠(mmol/24 h)51.4548.6658.2266.5662.7346.7346.2873.759.22
肿瘤直径(cm)3.02.02.14.52.23.33.01.04.5
随访时间(月)11680887189645964
术后血压(mmHg)120/73120/80130/80160/120115/80120/70130/80120/70130/80
术后血钾(mmol/L)3.503.533.803.813.624.094.083.703.73
), ArticleFig(id=1208144418356441966, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, language=EN, label=Tab.2, caption=

Renin and aldosterone examinations in both supine and upright positions of 9 patients with renin secreting tumor

, figureFileSmall=null, figureFileBig=null, tableContent=
指标患者编号
1a2a3a4a5a6a7a8b9b
肾素
 卧位PRA[μg/(L·h)]>12.07.89.815.99.13.46.6––
 立位PRA[μg/(L·h)]>12.012.012.816.4>12.05.26.3––
 卧位DRC(μU/ml)–––––––>500.0>500.0
 立位DRC(μU/ml)–––––––>500.0–
PAC(pmol/L)
 卧位447.4713.0483.0925.2534.1427.2386.2590.0440.4
 立位709.6740.7637.3973.1880.7519.8515.41764.5–
术后PRA(N-S)[μg/(L·h)]0.60.14.90.82.22.31.2––
术后DRC(N-S)(μU/ml)–––––––0.3–
术后PAC(N-S)(pmol/L)540.7608.9528.9538.9459.5528.5425.6534.2–
), ArticleFig(id=1208144418478076788, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208144411486171698, language=CN, label=表2, caption=

9例肾素分泌瘤患者的肾素-醛固酮卧、立位试验检查结果

, figureFileSmall=null, figureFileBig=null, tableContent=
指标患者编号
1a2a3a4a5a6a7a8b9b
肾素
 卧位PRA[μg/(L·h)]>12.07.89.815.99.13.46.6––
 立位PRA[μg/(L·h)]>12.012.012.816.4>12.05.26.3––
 卧位DRC(μU/ml)–––––––>500.0>500.0
 立位DRC(μU/ml)–––––––>500.0–
PAC(pmol/L)
 卧位447.4713.0483.0925.2534.1427.2386.2590.0440.4
 立位709.6740.7637.3973.1880.7519.8515.41764.5–
术后PRA(N-S)[μg/(L·h)]0.60.14.90.82.22.31.2––
术后DRC(N-S)(μU/ml)–––––––0.3–
术后PAC(N-S)(pmol/L)540.7608.9528.9538.9459.5528.5425.6534.2–
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肾素分泌瘤9例临床特征分析并文献复习
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刘兰荣 1, 2 , 陈康 1, * , 郑领涛 1, 3 , 巴建明 1 , 谷伟军 1 , 吕朝晖 1 , 母义明 1
解放军医学杂志 | 临床研究 2022,47(3): 258-263
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解放军医学杂志 | 临床研究 2022, 47(3): 258-263
肾素分泌瘤9例临床特征分析并文献复习
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刘兰荣1, 2, 陈康1, * , 郑领涛1, 3, 巴建明1, 谷伟军1, 吕朝晖1, 母义明1
作者信息
  • 1解放军总医院第一医学中心内分泌科，北京 100853
  • 2成武县人民医院内分泌科，山东菏泽 274200
  • 3邢台市人民医院内分泌科，河北邢台 054000

    • 刘兰荣，医学硕士，主治医师，主要从事内分泌基础与临床方面的研究

通讯作者:

陈康，E-mail：
Analysis of clinical features of 9 patients with renin secreting tumor and literature review
Lan-Rong Liu1, 2, Kang Chen1, * , Ling-Tao Zheng1, 3, Jian-Ming Ba1, Wei-Jun Gu1, Zhao-Hui Lv1, Yi-Ming Mu1
Affiliations
  • 1Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
  • 2Department of Endocrinology, the People's Hospital of Chengwu County, Heze, Shandong 274200, China
  • 3Department of Endocrinology, the People's Hospital of Xingtai, Xingtai, Hebei 054000, China
出版时间: 2022-03-28 doi: 10.11855/j.issn.0577-7402.2022.03.0258
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摘要
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目的 分析9例肾素分泌瘤患者的临床特征并进行相关文献复习，以提高对该病的认识及诊疗水平。方法 收集解放军总医院第一医学中心2010年1月－2020年2月收治的9例肾素分泌瘤患者的临床资料、诊治情况、病理和免疫组化染色结果进行回顾性分析。检索2001－2020年的相关数据库，结合文献报道的142例患者分析肾素分泌瘤的临床特点。结果 9例患者平均年龄22.6岁，均表现为高血压，7例为低钾血症。所有患者血浆肾素水平均明显高于正常，醛固酮水平高于正常参考区间中位数。术后病理证实均为肾球旁细胞瘤。免疫组化染色结果显示肿瘤细胞肾素、波形蛋白和CD34均呈阳性，部分肿瘤细胞平滑肌肌动蛋白(SMA)和突触素(Syn)呈阳性，S-100蛋白(S-100)和嗜铬素A(CgA)均呈阴性。术后所有患者血压和血钾水平恢复正常。2001－2020年共报道我国肾素分泌瘤患者142例，首发症状均为高血压，87例为低钾血症，93例血肾素与醛固酮水平增高，随访所有患者均未出现复发及转移情况。结论 肾素分泌瘤多为肾良性肿瘤，临床表现为高血压、低血钾、高肾素、高醛固酮血症的特点，该病可手术治疗，一般预后良好。

肾素分泌瘤  /  肾球旁细胞瘤  /  肾素  /  醛固酮  /  高血压

Objective To analyze the clinical features of 9 patients with renin secreting tumor and review the related literature in order to improve the understanding, diagnosis and treatment of the disease. Methods The clinical data, diagnosis, treatment, pathological and immunohistochemical profiles of 9 patients with renin secreting tumor admitted in the First Medical Center of Chinese PLA General Hospital from January 2010 to February 2020 were retrospectively analyzed. The literature was searched by retrieving the related database from 2001 to 2020, combined with 142 similar cases collected by searching the database to analyze the clinical features of patients with renin secreting tumor. Results All the 9 patients with an average age of 22.6 years presented with hypertension, and 7 of the 9 with hypokalemia. The plasma renin levels in all the patients were significantly higher than normal range, and the plasma aldosterone levels were above the median normal reference interval. Postoperative pathological examination of all cases confirmed juxtaglomerular cell tumor. Immunohistochemical staining showed that all the tumor cell renin, vimentin and CD34 were positive, some neoplastic cells were positive for smooth muscle actin (SMA) and synaptophysin (Syn), and negative for S-100 protein (S-100) and chromogranin A (CgA). The blood pressure and serum potassium level returned to normal range in all patients after surgery. A total of 142 patients with renin secreting tumor have been reported in China from 2001 to 2020.Hypertension was the initial symptom of all the patients. Hypokalemia occurred in 87 of 142 patients. Plasma renin and aldosterone levels were above the normal range in 93 patients. No recurrence or metastasis occurred in all patients after surgery during follow-up. Conclusions Renin secreting tumor mostly is characterized as benign renal tumor with hypertension, hypokalemia, hyperreninemia and hyperaldosteronism. Surgery is preferred in treatment of this tumor for a good prognosis.

renin secretory tumor  /  juxtaglomerular cell tumor  /  renin  /  aldosterone  /  hypertension
刘兰荣, 陈康, 郑领涛, 巴建明, 谷伟军, 吕朝晖, 母义明. 肾素分泌瘤9例临床特征分析并文献复习. 解放军医学杂志, 2022 , 47 (3) : 258 -263 . DOI: 10.11855/j.issn.0577-7402.2022.03.0258
Lan-Rong Liu, Kang Chen, Ling-Tao Zheng, Jian-Ming Ba, Wei-Jun Gu, Zhao-Hui Lv, Yi-Ming Mu. Analysis of clinical features of 9 patients with renin secreting tumor and literature review[J]. Medical Journal of Chinese People’s Liberation Army, 2022 , 47 (3) : 258 -263 . DOI: 10.11855/j.issn.0577-7402.2022.03.0258
正文
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肾素分泌瘤，又称肾球旁细胞瘤或肾素瘤，是一种罕见的以分泌肾素为特征的肾良性肿瘤。肾素分泌瘤释放大量肾素，刺激醛固酮分泌增加，从而引起高血压和低血钾的相关临床症状[1]。该病于1967年由Robertson等[2]首次报道，目前国内文献报道不足200例[1,3-4]，关于其免疫组化染色及肾素醛固酮功能试验在临床诊断中的作用研究较少，现报告解放军总医院第一医学中心诊治的9例肾素分泌瘤患者的临床特征、免疫组化染色及肾素醛固酮功能试验结果及其诊断价值，以提高临床医师对该病的认识和诊治水平。
1 病例资料
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1.1 研究对象
收集2010年1月－2020年2月在解放军总医院第一医学中心诊断为肾素分泌瘤的9例患者的一般临床资料、诊断方法、手术方式、术后病理、免疫组化染色结果及随访资料进行回顾性分析。本研究获解放军总医院伦理委员会批准[院科字(2020-46)号]。
1.2 肾素-醛固酮卧、立位试验
检测流程见文献[5]。所有患者于检查前保持正常钠盐饮食，停用醛固酮受体拮抗剂、保钾利尿剂、排钾利尿剂及甘草提炼物4周，停用血管紧张素转换酶抑制剂、血管紧张素受体拮抗剂、钙离子拮抗剂、β受体阻滞剂及非甾体类抗炎药至少2周，若血压难以控制，可使用α受体阻滞剂及非二氢吡啶类钙离子拮抗剂控制血压。低血钾患者需补钾至正常后再行检查。受试者平卧位休息8 h以上，清晨8:00卧位釆血测肾素、醛固酮水平，保持立位走动4 h，再次釆血测肾素、醛固酮水平(试剂盒购自北京北方生物技术研究所)。
1.3 病理和免疫组化染色
由解放军总医院第一医学中心病理科完成[6]。所有标本均经4%中性甲醛固定，常规脱水，石蜡包埋，4 μm厚切片，常规HE染色后于光镜下观察，每例患者均选取一块具代表性的组织进行免疫组化染色。免疫组化染色采用SP法，高温高压抗原修复，DAB显色，检测肾素、波形蛋白、CD34、肌动蛋白(Actin)、角蛋白(CK)、突触素(Syn)、核蛋白(Ki-67)、S-100、平滑肌肌动蛋白(SMA)、嗜铬素A(CgA)在肿瘤组织中的表达情况。所用抗体均购自北京中杉金桥生物技术有限公司。
1.4 基本特征
1.4.1 一般临床特征
9例中男6例，女3例，年龄14~30岁(平均22.6岁)。肿瘤均为单侧单发，位于右肾5例，左肾4例。9例入院时均表现为重度高血压，一般抗高血压药物治疗效果不佳，4例伴头痛症状，3例伴夜尿增多(最多达7~8次/夜)，2例出现头晕和恶心呕吐，2例出现视力下降症状。3例(例1、6、8)出现严重并发症，例1妊娠期间出现胎死宫内，例6因高血压导致脑出血，例8出现高血压性视盘水肿。9例高血压病程0.5~84.0个月，中位病程12个月，收缩压范围180~240 mmHg，舒张压范围110~150 mmHg(1 mmHg=0.133 kPa)，使用1~4种降压药(血管紧张素转换酶抑制剂或血管紧张素Ⅱ受体阻滞剂，β受体阻滞剂，钙通道阻滞剂，特拉唑嗪或螺内酯等其他药物)后，血压控制范围为收缩压120~240 mmHg，舒张压70~160 mmHg。实验室检查显示，9例患者血常规、肝肾功能、甲状腺功能、儿茶酚胺和皮质醇节律未见明显异常，低血钾7例(77.8%)，最低血钾水平1.90~3.07 mmol/L(参考范围3.50~5.50 mmol/L)，伴24 h尿钾增多，2例血钾水平正常。9例24 h尿醛固酮水平为9.40~86.30(31.93±24.03) μg/24 h(参考范围1.19~28.10 μg/24 h)。临床资料详见表1。
1.4.2 实验室检查结果
对9例患者行卧立位试验[5]，患者8和患者9采用化学发光法测定血浆直接肾素浓度(direct renin concentration，DRC)和血浆醛固酮浓度(plasma aldosterone concentration，PAC)。患者8结果显示卧位DRC>500.0 μU/ml，立位DRC>500.0 μU/ml(参考范围：卧位DRC 2.8~39.9 μU/ml，立位DRC 4.4~46.1 μU/ml)；卧位PAC 590.0 pmol/L，立位PAC 1764.5 pmol/L(参考范围：卧位PAC 83.1~653.7 pmol/L，立位PAC 83.1~977.8 pmol/L，1 ng/dl=27.7 pmol/L)。患者9卧位DRC>500.0 μU/ml，卧位PAC 440.4 pmol/L。患者1~7采用放射免疫法测定血浆肾素活性(plasma renin activity，PRA)及血浆PAC，患者卧位PRA水平为3.4~12.0(8.67±3.07) μg/(L·h)，均明显高于正常范围上限，立位后PRA水平[(11.03±3.92) μg/(L·h)]进一步升高[参考范围：卧位PRA<0.79 μg/(L·h)，立位PRA为0.93~6.56 μg/(L·h)，1 μU/ml=8.2 μg/(L·h)]；卧位PAC水平为386.2~925.2(559.44±193.17) pmol/L，立位PAC水平为515.4~973.1(710.94±172.54) pmol/L(参考范围：卧位PAC 163.4~481.9 pmol/L，立位PAC 180.1~819.9 pmol/L)，均高于正常参考区间中位数(表2)。检查结果显示所有患者血浆肾素水平均明显高于正常，PAC水平高于正常参考区间中位数，提示患者患有继发性醛固酮增多症的可能大。
1.4.3 影像学检查
9例均行肾血管超声检查，排除肾动脉狭窄。9例行肾脏B超检查，其中7例提示肾脏占位病变(5例为中等或偏高回声影，形态较规则，边界较清楚；2例为低回声影，形态欠规则)，另2例肾B超检查未发现占位病变。9例均行肾脏CT平扫+增强扫描检查，8例提示肾脏占位病变(6例表现为实性团块，多呈低或等密度，边界清晰；1例呈低密度团块，边界不清；1例表现为高密度团块，边界清晰，增强扫描可见延迟强化)，1例未发现占位病变。对于肾脏CT检查未发现病变及呈非典型征象的4例患者进行肾脏MRI检查，均发现肾脏占位病变，T1加权像呈等强度信号，T2加权像呈低强度信号，增强扫描显示皮质期未见明显强化(图1)。3例行分侧肾静脉采血检查，结果显示1例患侧肾静脉肾素水平明显高于对侧肾静脉(两侧肾静脉肾素比值>1.5)。
1.5 手术、病理及免疫组化染色
9例血压、血钾稳定后均给予腹腔镜下保留肾单位肾部分切除术，手术顺利，无并发症发生。术后肿物病理报告均为肾球旁细胞瘤(图2)，肿瘤均为单侧、单发，位于肾实质内，呈圆形或类圆形，肿瘤切面呈灰黄色或灰白色，实性，质地软或中等，肿瘤直径范围1.0~4.5 cm，8例包膜完整，1例侵犯肾盂及肾被膜。9例肿瘤免疫组化染色(采用SP法染色)结果均检测到肿瘤细胞肾素、CD34和波形蛋白的免疫反应性，6/6例Syn阳性，5/5例SMA阳性，2/8例CK阳性，2/4例Actin阳性，9/9例S-100和CgA阴性，CD117在3例检测患者中均呈阴性，Ki-67免疫组化染色阳性指数为1.0%~15.0%。
1.6 随访
截止到2020年2月，随访时间为4~116个月。9例血钾水平均恢复正常；8例术后血压恢复正常，另1例患者血压明显改善，服用单一药物(硝苯地平缓释片)血压可控制在正常范围；术后所有患者复查血浆肾素和醛固酮水平均恢复至正常范围(表2)。术后随访均未出现复发及转移情况。患者1术后2年再次妊娠并顺利生下一名男婴，母亲和婴儿均健康。
2 文献检索与复习
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通过检索PubMed、中国知网、万方数据库，采用关键词中文“肾球旁细胞瘤”“肾素瘤”和英文“juxtaglomerular cell tumor”“reninoma”进行检索。自2001－2020年报道关于我国肾球旁细胞瘤的文献共44篇，多为个案及短篇报道，英文短篇报道6篇，总病例数共142例。对纳入文献的临床资料特征、实验室和影像学检查、术后组织病理学检查及随访情况等分析如下。
2.1 临床资料特征
142例中男57例，女85例，大部分患者年龄为18~40岁，5例<18岁(年龄9~16岁)，2例老年患者年龄分别为70岁和72岁。所有患者首发症状均为高血压，收缩压范围140~240 mmHg，舒张压范围70~170 mmHg。靶器官损害评估方面的文献报道较少，6例有眼底动脉硬化表现，4例尿蛋白阳性，1例高血压危象伴可逆性后部脑病综合征，35例出现严重头痛、头晕及恶心呕吐症状，1例出现脑出血，2例出现妊娠重度子痫。
2.2 实验室及影像学检查
(1)87例(61.3%)存在低钾血症；(2)110例检查了血肾素、醛固酮水平，93例肾素与醛固酮水平增高，占检测患者的84.5%；(3)142例中，15例(10.6%)进行了分侧肾静脉取血PRA测定，其中4例阳性；(4)24例行肾MRI检查，结果显示肾脏实性占位，边界清楚，部分呈等T1长T2信号影，强化后见病变不均匀增强；(5)几乎所有患者行CT检查，CT平扫结果显示为单发、类圆形占位，位于肾皮质区，部分边缘不清，CT值与正常肾实质相近，部分病例增强后CT值轻中度强化。
2.3 术后组织病理学检查和随访情况
患者均行肾切除术或保留肾单位的肿瘤切除术。其中仅1例病理组织学检查考虑为具有恶性潜能的肾素分泌瘤，其余均为良性肿瘤。所有患者术后随访未出现复发及转移情况。
3 讨论
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肾素分泌瘤多为肾良性肿瘤，常见于青年人，平均年龄为24.5岁[7]，典型的临床表现为高血压、低血钾、高肾素、高醛固酮血症。本研究中9例肾素分泌瘤患者平均诊断年龄为22.6(10~30)岁，与Faucon等[8]的结果相仿。Dong等[7]根据患者临床表现将肾素分泌瘤分为3种类型：典型(血压高、血钾低，最常见)、非典型(血压高、血钾水平正常)和无功能型(血压、血钾水平均正常，病理确诊)。按该分类本研究中7例为典型肾素分泌瘤，2例为非典型肾素分泌瘤。
肾素分泌瘤作为一种以分泌肾素为特征的良性肿瘤，血肾素水平升高并出现继发性高醛固酮血症，首先需排除继发性肾素分泌增多的疾病，包括导致全身有效血容量减少的疾病(如肝、肾、心脏疾病，失盐性肾病，肾小管性酸中毒等)和引起肾脏局部灌注压降低的疾病(如肾动脉狭窄、恶性高血压、慢性肾脏疾病)等。本研究中患者肝肾功能正常，超声或CT检查未发现肾动脉狭窄、心脏疾病等，因而排除了继发性肾素分泌增多的疾病，考虑为原发性肾素分泌增多，再结合影像学检查，排除分泌肾素的肾外其他肿瘤如Wilms瘤等，最终考虑肾素分泌瘤的可能性大。
此外，肾素分泌瘤作为一种罕见的继发性高血压的病因，应与其他引起继发性高血压的疾病如原发性醛固酮增多症(PA)[9-10]相鉴别。PA占难治性高血压的20%[11-12]，影像学检查和卧立位试验在鉴别诊断中具有重要作用。肾素分泌瘤与PA的主要区别在于肾素水平[4,9]，肾素分泌瘤患者无论卧位还是立位，肾素水平通常升高，而PA患者的肾素水平降低[9]。
影像学检查可协助术前定位。9例患者均行肾脏B超检查，漏诊2例，可能是由于其空间分辨率有限所致。有研究表明，肾素分泌瘤大多可以通过肾脏CT检查确定，对于CT检查误认为囊肿或小肿瘤者，肾脏MRI检查能更好地鉴别[8]。本研究9例患者行肾脏CT检查，其中1例未发现病变，进一步行肾脏MRI检查后发现肿瘤，因此，对于较小的肿瘤肾脏MRI检查优于CT。有研究主张一旦在影像学上发现病变，应使用分侧肾静脉取血证实肾素分泌瘤的诊断[13]，也有研究认为该检查阳性率不高，且操作复杂，不推荐使用[4]。本研究也证实，3例患者肾静脉取样仅1例阳性，提示该检查阳性率不高。
肾素分泌瘤的初步诊断依赖于患者高血压、低血钾的临床特征，肾素和醛固酮水平及影像学检查结果，最终诊断则取决于病理检查。本组患者的组织学和电镜特征与既往报道一致，肾素、CD34和波形蛋白均为肾素分泌瘤的阳性标志物[3-4,9]。此外，6例检测了Syn，均为阳性，提示肾素分泌瘤具有神经内分泌性质，CgA检测为阴性，提示CgA可能不是肾素分泌瘤的生物标志物。
Ki-67作为细胞增殖的标记物，在肾素分泌瘤中的研究较少，本研究中Ki-67阳性指数为3%~15%，而Wang等[3]发现Ki-67指数多<2%，个别可能高达10%，与本研究结果明显不同。通常肾素分泌瘤被认为是一种良性肿瘤，但也有关于肿瘤复发、血管侵犯和转移的报道[14-16]。本研究对患者随访4~116个月未发现转移和复发病例，但对于相对较大(直径>5 cm)及Ki-67指数较高者，建议长期随访。
肾素分泌瘤治疗上首选外科手术切除，腹腔镜下保留肾单位的肾部分切除术是一种可行且有效的治疗方法，可最大限度保留患者的肾功能，并可治愈高血压[4,9]。术前应考虑患者血压和血流动力学的稳定性，肾素-血管紧张素-醛固酮系统阻断剂是控制血压的最佳药物[10]，但应强调起始低剂量用药并密切监测患者血压。本研究患者均行腹腔镜下保留肾单位的肾部分切除术，术前给予肾素-血管紧张素-醛固酮系统阻断剂降压及补钾对症处理，术中9例患者血压未出现明显波动，与既往报道一致[17]。有研究报道，约10%的患者在肾切除术后仍存在高血压[18-19]。本研究中9例患者术后血钾、肾素、醛固酮水平均恢复正常，8例血压恢复正常，1例口服1种降压药物即可使血压控制在正常范围，考虑可能的原因为患者高血压病程较长，动脉血管已发生了硬化。
综上所述，肾素分泌瘤多为肾良性肿瘤，当青年患者出现高血压、低血钾、高肾素和醛固酮水平的临床特征时，应考虑到肾素分泌瘤的可能。患者的临床特征，肾素、醛固酮水平及影像学检查可协助肾素分泌瘤术前诊断，确诊依赖于病理诊断；肿瘤对肾素、CD34、波形蛋白、SMA、Syn的免疫反应性可协助其病理诊断；该病可手术治疗，一般预后良好。但本研究为回顾性研究，患者仅9例，由于客观条件的限制，未对患者的染色体和基因进行分析研究。有报道发现肾素分泌瘤的发生与4、10号染色体上部分促癌基因的过表达或9、11号染色体上部分抑癌基因缺失有关[20-21]。因此，肾素分泌瘤的发病机制仍有待通过大样本的染色体和基因研究进行探讨。
基金
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  • 北京市科技计划课题(D141107005314004)
文献
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参考文献 引证文献
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2022年第47卷第3期
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doi: 10.11855/j.issn.0577-7402.2022.03.0258
  • 接收时间：2021-09-27
  • 首发时间：2025-12-17
  • 出版时间：2022-03-28
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  • 收稿日期：2021-09-27
  • 录用日期：2021-11-18
基金
Science and Technology Project of Beijing(D141107005314004)
北京市科技计划课题(D141107005314004)
作者信息
    1解放军总医院第一医学中心内分泌科，北京 100853
    2成武县人民医院内分泌科，山东菏泽 274200
    3邢台市人民医院内分泌科，河北邢台 054000

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2种不同金属材料的力学参数
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species		 占总种数比例
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total species (%)		 属
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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