Mutation Type and Intracranial Aneurysm Formation in Autosomal Dominant Polycystic Kidney Disease
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-09-01
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| Series: | Stroke: Vascular and Interventional Neurology |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/SVIN.121.000203 |
| _version_ | 1811154676407599104 |
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| author | Hiroshi Kataoka Hiroyuki Akagawa Yusuke Ushio Masayo Sato Shun Manabe Shiho Makabe Keiko Kawachi Taro Akihisa Naomi Iwasa Rie Yoshida Ken Tsuchiya Kosaku Nitta Toshio Mochizuki |
| author_facet | Hiroshi Kataoka Hiroyuki Akagawa Yusuke Ushio Masayo Sato Shun Manabe Shiho Makabe Keiko Kawachi Taro Akihisa Naomi Iwasa Rie Yoshida Ken Tsuchiya Kosaku Nitta Toshio Mochizuki |
| author_sort | Hiroshi Kataoka |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T04:21:08Z |
| format | Article |
| id | doaj.art-d5ed69fea6b14f22aa695deb4044646a |
| institution | Directory Open Access Journal |
| issn | 2694-5746 |
| language | English |
| last_indexed | 2024-04-10T04:21:08Z |
| publishDate | 2022-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stroke: Vascular and Interventional Neurology |
| spelling | doaj.art-d5ed69fea6b14f22aa695deb4044646a2023-03-11T07:58:11ZengWileyStroke: Vascular and Interventional Neurology2694-57462022-09-012510.1161/SVIN.121.000203Mutation Type and Intracranial Aneurysm Formation in Autosomal Dominant Polycystic Kidney DiseaseHiroshi Kataoka0Hiroyuki Akagawa1Yusuke Ushio2Masayo Sato3Shun Manabe4Shiho Makabe5Keiko Kawachi6Taro Akihisa7Naomi Iwasa8Rie Yoshida9Ken Tsuchiya10Kosaku Nitta11Toshio Mochizuki12Department of Nephrology Tokyo Women's Medical University Tokyo JapanTokyo Women's Medical University Institute for Integrated Medical Sciences Tokyo JapanDepartment of Nephrology Tokyo Women's Medical University Tokyo JapanDepartment of Nephrology Tokyo Women's Medical University Tokyo JapanDepartment of Nephrology Tokyo Women's Medical University Tokyo JapanDepartment of Nephrology Tokyo Women's Medical University Tokyo JapanDepartment of Nephrology Tokyo Women's Medical University Tokyo JapanDepartment of Nephrology Tokyo Women's Medical University Tokyo JapanDepartment of Nephrology Tokyo Women's Medical University Tokyo JapanDepartment of Nephrology Tokyo Women's Medical University Tokyo JapanDepartment of Blood Purification Tokyo Women's Medical University Tokyo JapanDepartment of Nephrology Tokyo Women's Medical University Tokyo JapanDepartment of Nephrology Tokyo Women's Medical University Tokyo JapanBackground 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.https://www.ahajournals.org/doi/10.1161/SVIN.121.000203autosomal dominant polycystic kidney diseaseintracranial aneurysmsmutationssplicing mutationsubstitutionuniversal screening |
| spellingShingle | Hiroshi Kataoka Hiroyuki Akagawa Yusuke Ushio Masayo Sato Shun Manabe Shiho Makabe Keiko Kawachi Taro Akihisa Naomi Iwasa Rie Yoshida Ken Tsuchiya Kosaku Nitta Toshio Mochizuki Mutation Type and Intracranial Aneurysm Formation in Autosomal Dominant Polycystic Kidney Disease Stroke: Vascular and Interventional Neurology autosomal dominant polycystic kidney disease intracranial aneurysms mutations splicing mutation substitution universal screening |
| title | Mutation Type and Intracranial Aneurysm Formation in Autosomal Dominant Polycystic Kidney Disease |
| title_full | Mutation Type and Intracranial Aneurysm Formation in Autosomal Dominant Polycystic Kidney Disease |
| title_fullStr | Mutation Type and Intracranial Aneurysm Formation in Autosomal Dominant Polycystic Kidney Disease |
| title_full_unstemmed | Mutation Type and Intracranial Aneurysm Formation in Autosomal Dominant Polycystic Kidney Disease |
| title_short | Mutation Type and Intracranial Aneurysm Formation in Autosomal Dominant Polycystic Kidney Disease |
| title_sort | mutation type and intracranial aneurysm formation in autosomal dominant polycystic kidney disease |
| topic | autosomal dominant polycystic kidney disease intracranial aneurysms mutations splicing mutation substitution universal screening |
| url | https://www.ahajournals.org/doi/10.1161/SVIN.121.000203 |
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