Renin-independent aldosteronism and chronic kidney disease in diabetes: Observational and Mendelian randomization analyses

作者全名："Hu, Jinbo; Chen, Xiangjun; Luo, Yi; Yang, Jun; Zeng, Qinglian; Luo, Wenjin; Shu, Xiaoyu; Cheng, Qingfeng; Gong, Lilin; Wang, Zhihong; Li, Qifu; Yang, Shumin"

作者地址："[Hu, Jinbo; Chen, Xiangjun; Luo, Yi; Zeng, Qinglian; Luo, Wenjin; Cheng, Qingfeng; Gong, Lilin; Wang, Zhihong; Li, Qifu; Yang, Shumin] Chongqing Med Univ, Dept Endocrinol, Affiliated Hosp 1, Chongqing, Peoples R China; [Luo, Yi] Chongqing Med Univ, Bishan Hosp Chongqing, Bishan Hosp, Chongqing, Peoples R China; [Yang, Jun] Hudson Inst Med Res, Ctr Endocrinol & Metab, Clayton, Vic, Australia; [Yang, Jun] Monash Univ, Dept Med, Clayton, Vic, Australia; [Shu, Xiaoyu] Capital Med Univ, Beijing Chao yang Hosp, Dept Endocrinol, Beijing, Peoples R China; [Wang, Zhihong; Li, Qifu; Yang, Shumin] Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi St, Chongqing 400016, Peoples R China"

通信作者："Wang, ZH; Li, QF; Yang, SM (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi St, Chongqing 400016, Peoples R China."

来源：METABOLISM-CLINICAL AND EXPERIMENTAL

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001058341000001

JCR分区：Q1

影响因子：10.8

年份：2023

卷号：145

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Renin-independent Aldosteronism; Diabetes; Chronic kidney disease; Mendelian randomization; Causal relationship

摘要："Background: Renin-independent aldosteronism (RIA) describes the spectrum of autonomous aldosterone secretion from mild to overt. We aimed to explore whether RIA is causally associated with chronic kidney disease (CKD) in patients with diabetes.Methods: We cross-sectionally included 1027, 402 and 39,709 patients with any type of diabetes from cohorts of EIMDS, CONPASS and UK Biobank, respectively. In EIMDS, we defined RIA and renin-dependent aldosteronism based on plasma aldosterone and renin concentrations. We performed captopril challenge test to confirm renindependent or independent aldosteronism in CONPASS. In UK Biobank, we generated genetic instruments for RIA based on the genome-wide association studies (GWAS). We extracted the corresponding single nucleotide polymorphisms (SNPs) information from the GWAS data of CKD in diabetes. We harmonized the SNP-RIA and SNP-CKD data to conduct the two-sample Mendelian randomization analyses.Findings: In EIMDS and CONPASS, when compared to subjects with normal aldosterone concentration or renindependent aldosteronism, participants with RIA had a lower estimated glomerular filtration rate, a higher prevalence of CKD, and a higher multivariate-adjusted odds ratio (OR) of CKD (OR 2.62 [95%CI 1.09-6.32] in EIMDS, and 4.31 [1.39-13.35] in CONPASS). The two-sample Mendelian randomization analysis indicated that RIA was significantly associated with a higher risk of CKD (inverse variance weighted OR 1.10 [95 % CI 1.05-1.14]), with no evidence of significant heterogeneity or substantial directional pleiotropy. Interpretation: Among patients with diabetes, renin-independent aldosteronism is causally associated with a higher risk of CKD. Targeted treatment of autonomous aldosterone secretion may benefit renal function in diabetes."

基金机构："National key research amp; development plan of China; major project of prevention and treatment for common diseases; National Natural Science Foundation of China, Major Joint Project; National Natural Science Foundation of China [2021YFC2501600, 2021YFC2501603]; Joint Medical Research Project of Chongqing Science and Technology Commission amp; Chongqing Health and Family Planning Commission (Major Project) [U21A20355]; Chongqing Science and Health Joint Medical Research Project [82270878, 81870567, 81970720, 82170825]; Innovative Funded Project of Chongqing Innovation and Retention Program [2022ZDXM003]; Chongqing Yong and Middle-aged Senior Medical Talents Studio [2020FYYX141]; Chongqing Outstanding Youth Funds [cx2019032]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [ZQNYXGDRCGZS2021001]; Program for Major Scientific and Technological Talents, Chongqing Medical University [cstc2019jcyjjq0006]; First batch of key Disciplines On Public Health in Chongqing"

基金资助正文："This work was supported by National key research & amp; development plan of China, major project of prevention and treatment for common diseases (2021YFC2501600, sub-project: 2021YFC2501603) . the National Natural Science Foundation of China, Major Joint Project (U21A20355) . The National Natural Science Foundation of China (82270878, 81870567, 81970720, 82170825) . Joint Medical Research Project of Chongqing Science and Technology Commission & amp; Chongqing Health and Family Planning Commission (Major Project, 2022ZDXM003) . The Chongqing Science and Health Joint Medical Research Project (2020FYYX141) . The Innovative Funded Project of Chongqing Innovation and Retention Program (cx2019032) . The Chongqing Yong and Middle-aged Senior Medical Talents Studio (ZQNYXGDRCGZS2021001) . Chongqing Outstanding Youth Funds (cstc2019jcyjjq0006) . Program for Youth Innovation in Future Medicine, Chongqing Medical University (Jinbo Hu and Rufei Gao) . Program for Major Scientific and Technological Talents, Chongqing Medical University (Jinbo Hu and Shumin Yang) . The First batch of key Disciplines On Public Health in Chongqing."