KCNJ5突变与单侧原发性醛固酮增多症术后临床缓解的相关性研究

常智; 尚吉文; 任瑞民; 任翔; 杨述尚; 郭志松

doi:10.13201/j.issn.1001-1420.2023.07.008

KCNJ5突变与单侧原发性醛固酮增多症术后临床缓解的相关性研究

- 1.
  山西医科大学第三医院(山西白求恩医院山西医学科学院同济山西医院)泌尿外科(太原，030032)
- 2.
  华中科技大学同济医学院附属同济医院泌尿外科
基金项目:
山西省重点研发计划项目(No：201903D321130)

详细信息

通讯作者: 尚吉文，E-mail：sjw139@126.com

中图分类号: R736.6

收稿日期: 2022-09-03

刊出日期: 2023-07-06

Correlation between KCNJ5 mutation and postoperative clinical remission of unilateral primary aldosteronism

- 1.
  Department of Urology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
- 2.
  Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

More Information

Corresponding author: SHANG Jiwen, E-mail: sjw139@126.com

Received Date: 03 September 2022

Publish Date: 06 July 2023

摘要

摘要: 目的研究KCNJ5基因突变与单侧原发性醛固酮增多症(primary aldosteronism, PA)术后临床缓解的相关性。方法回顾性分析2019年8月-2021年8月山西白求恩医院110例单侧PA患者的临床资料, 并进行腺瘤组织中KCNJ5基因的外显子扩增与测序, 以确定KCNJ5基因突变与患者临床特征的相关性。所有患者均行腹腔镜肾上腺肿瘤切除术。结果 110例患者中有65例(59.1%)发现了KCNJ5基因突变。所有患者术后1年内均获得生化完全缓解, 其中60例(54.5%)获得临床完全缓解。与未突变组相比, KCNJ5基因突变组的PA患者发病年龄更小(P=0.030)、高血压持续时间更短(P=0.046)、肿瘤直径更大(P=0.049)、术前血钾更低(P=0.025)、术前醛固酮/肾素比值(aldosterone-renin ratio, ARR)更高(P=0.042)。与未获得临床完全缓解的患者相比, 临床完全缓解的患者发生KCNJ5基因突变的比例更高(P < 0.001)、年龄更小(P=0.001)、高血压持续时间更短(P < 0.001)、术前血浆醛固酮浓度(plasma aldosterone concentration, PAC)的水平更高(P=0.022)、术前ARR更高(P=0.002)。多因素logistic回归分析结果显示, KCNJ5基因突变(OR=4.850, P=0.001)和高血压持续时间(OR=0.692, P=0.018)是术后获得临床完全缓解的独立影响因素。结论 KCNJ5基因突变和高血压持续时间是单侧PA患者术后获得临床完全缓解的独立预测因素。
- 原发性醛固酮增多症 /
- KCNJ5基因突变 /
- 临床缓解 /
- 高血压持续时间 /
- 原发醛固酮增多症手术结局标准
Abstract: Objective To explore the correlation between KCNJ5 mutations and postoperative clinical remission of unilateral primary aldosteronism (PA).Methods The clinical data of 110 patients with unilateral PA at Shanxi Bethune Hospital from August 2019 to August 2021 were retrospectively analyzed. The exons of KCNJ5 gene in adenoma tissues were amplified and sequenced to determine the correlation between KCNJ5 mutation and clinical features of patients before and after unilateral adrenalectomy. Laparoscopic adrenalectomy was performed in all PA patients.Results KCNJ5 mutations were identified in 65 of 110 patients with PA (59.1%). Complete biochemical remission was achieved in all patients within 1 year after adrenalectomy, among which 60(54.5%) achieved complete clinical remission. Compared with the KCNJ5 wild type group, patients harbouring KCNJ5 mutations had younger age (P=0.030), shorter duration of hypertension (P=0.046), larger tumor (P=0.049), lower preoperative serum potassium (P=0.025) and higher preoperative aldosterone-renin ratio (ARR)(P=0.042). Complete clinical remission patients presented the following characteristics: KCNJ5 mutation (P < 0.001), younger age (P=0.001), shorter duration of hypertension (P < 0.001), higher preoperative plasma aldosterone concentration (P=0.022) and higher preoperative ARR (P=0.002). Multivariate logistic regression analysis showed that KCNJ5 mutation (OR=4.850, P=0.001) and duration of hypertension (OR=0.692, P=0.018) were independent factors for complete clinical remission.Conclusion KCNJ5 mutation and duration of hypertension are independent predictors of complete clinical remission after unilateral adrenalectomy in patients with unilateral PA.
- primary aldosteronism /
- KCNJ5 mutation /
- clinical remission /
- duration of hypertension /
- primary aldosteronism surgical outcome consensus criteria

HTML全文

图 1 110例PA患者的基因突变情况

下载: 全尺寸图片幻灯片

表 1 KCNJ5突变组与非突变组的临床特征比较例(%)，M(P₂₅，P₇₅)

项目	非KCNJ5突变组(45例)	KCNJ5突变组(65例)	P值
性别			0.578
男	17(37.8)	28(43.1)
女	28(62.2)	37(56.9)
年龄/岁	52.0(44.5，58.0)	48.0(42.5，55.0)	0.030
高血压家族史			0.469
无	23(51.1)	33(50.8)
有	22(48.9)	32(49.2)
高血压持续时间/年	5.0(3.0，7.0)	4.0(2.0，5.5)	0.046
服用降压药种数/种	2.0(1.0，2.0)	2.0(1.0，2.0)	0.431
BMI/(kg/m²)	23.7(22.7，24.6)	24.0(23.1，24.7)	0.488
肿瘤直径^a)/cm	1.7(1.0，2.3)	2.1(1.5，2.7)	0.049
随访时间/月	9.0(7.0，11.0)	9.0(7.0，10.5)	0.798
术前SBP/mmHg	165.0(155.0，175.0)	160.0(155.0，175.0)	0.910
术前DBP/mmHg	105.0(97.5，110.0)	105.0(100.0，114.5)	0.426
术前血钾/(mmol/L)	3.4(3.2，3.4)	3.2(3.2，3.4)	0.025
术前PAC/(ng/dL)	31.6(26.1，37.2)	31.3(27.5，36.9)	0.745
术前ARR	124.0(67.5，233.0)	170.0(119.5，212.5)	0.042
术前eGFR/(mL/min/1.73m²)	64.8(59.5，79.2)	69.3(61.2，82.5)	0.162
注：BMI为体重指数，SBP为收缩压，DBP为舒张压。^a)肿瘤直径数据已除外7例UAH患者，其非KCNJ5突变组38例，KCNJ5突变组65例。

下载: 导出CSV

表 2 实现与未实现临床完全缓解组的临床及分子特征比较例(%)，M(P₂₅，P₇₅)

项目	非临床完全缓解组(50例)	临床完全缓解组(60例)	P值
KCNJ5突变			< 0.001
无	31(62.0)	14(23.3)
有	19(38.0)	46(76.7)
性别			0.571
男	19(38.0)	26(43.3)
女	31(62.0)	34(56.7)
年龄/岁	54.0(45.0，58.0)	46.5(42.0，53.5)	0.001
高血压家族史			0.222
无	30(60.0)	29(48.3)
有	20(40.0)	31(51.7)
高血压持续时间/年	5.0(3.0，7.0)	3.0(2.0，5.0)	< 0.001
服用降压药种数/种	2.0(1.0，2.0)	2.0(1.0，2.0)	0.584
BMI/(kg/m²)	24.1(23.0，25.4)	24.0(22.9，24.4)	0.222
肿瘤直径^a)/cm	1.8(1.2，2.6)	2.1(1.5，2.5)	0.472
随访时间/月	9.0(7.8，11.0)	8.5(7.0，10.0)	0.449
术前SBP/mmHg	165.0(155.0，176.3)	160.0(155.0，170.8)	0.344
术前DBP/mmHg	105.0(98.8，119.3)	105.0(100.0，110.0)	0.813
术前血钾/(mmol/L)	3.3(3.2，3.4)	3.3(3.2，3.4)	0.233
术前PAC/(ng/dL)	31.1(26.3，34.2)	33.2(27.2，39.7)	0.022
术前ARR	121.0(69.0，207.0)	174.0(125.0，246.0)	0.002
术前eGFR/(mL/min/1.73m²)	65.3(59.2，80.7)	67.8(61.8，81.9)	0.437
注：非临床完全缓解组包括临床部分缓解和临床未缓解。^a)肿瘤直径数据已除外7例UAH患者，其非临床完全缓解组47例，临床完全缓解组56例。

下载: 导出CSV

表 3 PA患者术后获得临床完全缓解的预测因素分析

变量	β	Wald	OR(95%CI)	P值
KCNJ5突变	1.579	10.405	4.850(1.858~12.658)	0.001
年龄	-0.047	1.223	0.954(0.879~1.037)	0.269
高血压持续时间	-0.368	5.550	0.692(0.509~0.940)	0.018
术前PAC	0.068	3.162	1.071(0.993~1.155)	0.075
术前ARR	0.004	2.180	1.004(0.999~1.009)	0.140

下载: 导出CSV

参考文献(20)

[1]	Hiramatsu K, Yamada T, Yukimura Y, et al. A screening test to identify aldosterone-producing adenoma by measuring plasma renin activity. Results in hypertensive patients[J]. Arch Intern Med, 1981, 141(12): 1589-1593. doi: 10.1001/archinte.1981.00340130033011
[2]	Vorselaars W, van Beek DJ, Postma EL, et al. Clinical outcomes after surgery for primary aldosteronism: Evaluation of the PASO-investigators' consensus criteria within a worldwide cohort of patients[J]. Surgery, 2019, 166(1): 61-68. doi: 10.1016/j.surg.2019.01.031
[3]	Choi M, Scholl UI, Yue P, et al. K⁺channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension[J]. Science, 2011, 331(6018): 768-772. doi: 10.1126/science.1198785
[4]	中华医学会内分泌学分会. 原发性醛固酮增多症诊断治疗的专家共识(2020版)[J]. 中华内分泌代谢杂志, 2020, 36(9): 727-736. doi: 10.3760/cma.j.cn311282-20200615-00444
[5]	Wang K, Hu J, Yang J, et al. Development and Validation of Criteria for Sparing Confirmatory Tests in Diagnosing Primary Aldosteronism[J]. J Clin Endocrinol Metab, 2020, 105(7): dgaa282.
[6]	Williams TA, Lenders J, Mulatero P, et al. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort[J]. Lancet Diabetes Endocrinol, 2017, 5(9): 689-699. doi: 10.1016/S2213-8587(17)30135-3
[7]	Sun DQ, Jin Y, Wang TY, et al. MAFLD and risk of CKD[J]. Metabolism, 2021, 115: 154433. doi: 10.1016/j.metabol.2020.154433
[8]	Zhang X, Zhu Z, Xu T, et al. Factors affecting complete hypertension cure after adrenalectomy for aldosterone-producing adenoma: outcomes in a large series[J]. Urol Int, 2013, 90(4): 430-434. doi: 10.1159/000347028
[9]	BiLiGe W, Wang C, Bao J, et al. Predicting factors related with uncured hypertension after retroperitoneal laparoscopic adrenalectomy for unilateral primary aldosteronism[J]. Medicine(Baltimore), 2019, 98(30): e16611.
[10]	Chang YY, Pan CT, Chen ZW, et al. KCNJ5 Somatic Mutations in Aldosterone-Producing Adenoma Are Associated with a Greater Recovery of Arterial Stiffness[J]. Cancers(Basel), 2021, 13(17): 4313.
[11]	Monticone S, D'Ascenzo F, Moretti C, et al. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis[J]. Lancet Diabetes Endocrinol, 2018, 6(1): 41-50. doi: 10.1016/S2213-8587(17)30319-4
[12]	任翔, 尚吉文, 任瑞民, 等. 原发性醛固酮增多症患者术后发生慢性肾功能不全的影响因素分析[J]. 中华泌尿外科杂志, 2020, 41(10): 731-735. https://cdmd.cnki.com.cn/Article/CDMD-10114-1021726081.htm
[13]	李慧, 卞晓洁, 叶定伟. 腹腔镜切除肾上腺醛固酮腺瘤的短期及长期随访研究[J]. 临床泌尿外科杂志, 2022, 37(3): 205-209. https://lcmw.chinajournal.net.cn/WKC/WebPublication/paperDigest.aspx?paperID=71ddc206-43f3-4d30-ada7-1e3b1961b1c4
[14]	Zheng FF, Zhu LM, Nie AF, et al. Clinical characteristics of somatic mutations in Chinese patients with aldosterone-producing adenoma[J]. Hypertension, 2015, 65(3): 622-628. doi: 10.1161/HYPERTENSIONAHA.114.03346
[15]	Wang B, Li X, Zhang X, et al. Prevalence and characterization of somatic mutations in Chinese aldosterone-producing adenoma patients[J]. Medicine(Baltimore), 2015, 94(16): e708.
[16]	Rege J, Turcu AF, Rainey WE. Primary aldosteronism diagnostics: KCNJ5 mutations and hybrid steroid synthesis in aldosterone-producing adenomas[J]. Gland Surg, 2020, 9(1): 3-13. doi: 10.21037/gs.2019.10.22
[17]	Gruber S, Beuschlein F. Hypokalemia and the Prevalence of Primary Aldosteronism[J]. HormMetab Res, 2020, 52(6): 347-356.
[18]	Okamura T, Nakajima Y, Katano-Toki A, et al. Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations[J]. Endocr J, 2017, 64(1): 39-47. doi: 10.1507/endocrj.EJ16-0243
[19]	Chang YY, Tsai CH, Peng SY, et al. KCNJ5 Somatic Mutations in Aldosterone-Producing Adenoma Are Associated With a Worse Baseline Status and Better Recovery of Left Ventricular Remodeling and Diastolic Function[J]. Hypertension, 2021, 77(1): 114-125. doi: 10.1161/HYPERTENSIONAHA.120.15679
[20]	Lu CC, Yen RF, Peng KY, et al. NP-59 Adrenal Scintigraphy as an Imaging Biomarker to Predict KCNJ5 Mutation in Primary Aldosteronism Patients[J]. Front Endocrinol(Lausanne), 2021, 12: 644927. doi: 10.3389/fendo.2021.644927