Mutation Type and Intracranial Aneurysm Formation in Autosomal Dominant Polycystic Kidney Disease

Author:

Kataoka Hiroshi12,Akagawa Hiroyuki3,Ushio Yusuke1,Sato Masayo1,Manabe Shun1,Makabe Shiho1,Kawachi Keiko1,Akihisa Taro1,Iwasa Naomi1,Yoshida Rie1,Tsuchiya Ken4,Nitta Kosaku1,Mochizuki Toshio12ORCID

Affiliation:

1. Department of Nephrology Tokyo Women's Medical University Tokyo Japan

2. Clinical Research Division for Polycystic Kidney Disease Department of Nephrology Tokyo Women's Medical University Tokyo Japan

3. Tokyo Women's Medical University Institute for Integrated Medical Sciences Tokyo Japan

4. Department of Blood Purification Tokyo Women's Medical University Tokyo Japan

Abstract

Background Screening for intracranial aneurysms (IAs) in patients with risk factors of IA is recommended. However, genetic risk factors of IA in patients with autosomal dominant polycystic kidney disease (ADPKD) remain unclear, and genotype–phenotype relationships in IAs in patients with ADPKD have not been clarified. Therefore, we aimed to clarify the associations between germline mutations and IA formation in patients with ADPKD. Methods A total of 135 patients with ADPKD who were evaluated for ADPKD mutations were examined for IA formation in this single‐center observational study. Results The incidence of de novo IA formation was 1.3% per patient‐year. Age at IA diagnosis was younger in patients with frameshift (median, 36 years; P =0.003) and splicing mutations (median, 43 years; P =0.046) than in patients with substitutions (median, 63 years). Multivariable analyses showed that IA was associated with female sex (odds ratio [OR], 3.32 [95% CI, 1.10–10.01]; P =0.03), a family history of IA or subarachnoid hemorrhage (OR, 3.05 [95% CI, 1.07–8.71]; P =0.04), estimated glomerular filtration rate (OR, 0.69 [95% CI, 0.54–0.87]; P =0.002), and splicing mutations (OR, 9.30 [95% CI, 1.71–50.44]; P =0.01). Splicing mutations showed a significant association with IA formation even in subcohorts with minimal risk factors for IA, such as age <50 years (OR, 19.52 [95% CI, 3.22–118.51]; P =0.001), nonhypertension (OR, 49.28 [95% CI, 3.60–673.98]; P =0.004), and nonsmoking behavior (OR, 27.79 [95% CI, 3.49–221.21]; P =0.002). Conversely, substitutions showed significant associations with IA formation in subcohorts such as age ≥50 years (OR, 8.66; 95% CI, 1.43–52.51; P =0.02) and chronic kidney disease stages 4 and 5 (OR, 10.70 [95% CI, 1.05–108.75]; P =0.045). Conclusions Genetic analyses in patients with ADPKD could contribute to IA screening and could be useful for evaluating the prognosis, including complications. IA screening should be recommended for patients with ADPKD who have splicing and frameshift mutations and for older patients or patients with advanced ADPKD who have substitutions.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3