KCNJ5 Mutation is a Predictor for Recovery of Endothelial Function After Adrenalectomy in Patients with Aldosterone-producing Adenoma

Overview

Journal Hypertens Res

Specialty Cardiology & Vascular Diseases

Date 2023 Jul 18

PMID 37463983

Authors

Shinji Kishimoto

Kenji Oki

Tatsuya Maruhashi

Masato Kajikawa

Aya Mizobuchi

Takahiro Harada

Takayuki Yamaji

Yu Hashimoto

Kenichi Yoshimura

Yukiko Nakano

Chikara Goto

Farina Mohamad Yusoff

Ayumu Nakashima

Yukihito Higashi

Affiliations

Soon will be listed here.

Abstract

The relationship of KCNJ5 mutation with vascular function and vascular structure in aldosterone-producing adenoma (APA) patients before and after adrenalectomy remains unclear. The purpose of this study was to evaluate the influence of KCNJ5 mutation on vascular function and vascular structure in APA and the effects of adrenalectomy on vascular function and vascular structure in APA patients with and those without KCNJ5 mutation. Flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation (NID), brachial artery intima-media thickness (IMT), and brachial-ankle pulse wave velocity (baPWV) were measured to assess vascular function and vascular structure in 46 APA patients with KCNJ5 mutation and 23 APA patients without KCNJ5 mutation and in 69 matched pairs of patients with essential hypertension (EHT). FMD, NID, brachial IMT and baPVW were evacuated before adrenalectomy and at 12 weeks after adrenalectomy in APA patients with KCNJ5 mutation and APA patients without KCNJ5 mutation. FMD and NID were significantly lower in APA patients than in patients with EHT. There was no significant difference in FMD or NID between patients with and those without KCNJ5 mutation. In APA patients with KCNJ5 mutation, FMD and NID after adrenalectomy were significantly higher than those before adrenalectomy. In APA patients without KCNJ5 mutation, only NID after adrenalectomy was significantly higher than that before adrenalectomy. Endothelial function in APA patients with KCNJ5 mutation was improved by adrenalectomy in the early postoperative period. KCNJ5 mutation is a predictor for early resolution of endothelial function by adrenalectomy. This study was approved by principal authorities and ethical issues in Japan (URL for Clinical Trial: http://www.umin.ac.jp/ctr/index.htm Registration Number for Clinical Trial: UMIN000003409).

Citing Articles

ccfDNA analysis for the classification of adrenocortical adenomas.

Xu M, Tourigny D, Lippert J, Crastin A, Appenzeller S, Asia M J Endocrinol Invest. 2025; .

PMID: 39891827 DOI: 10.1007/s40618-025-02540-5.

Current topic of vascular function in hypertension in 2023-2024.

Maruhashi T, Higashi Y Hypertens Res. 2024; 47(12):3310-3317.

PMID: 39300292 PMC: 11618089. DOI: 10.1038/s41440-024-01885-3.

Comparisons of risk factors for post-treatment renal dysfunction between the two major subtypes of primary aldosteronism.

Watanabe D, Morimoto S, Morishima N, Ichihara A Endocrine. 2023; 84(1):245-252.

PMID: 38087188 DOI: 10.1007/s12020-023-03627-w.

References

Loh K, Koay E, Khaw M, Emmanuel S, Young Jr W . Prevalence of primary aldosteronism among Asian hypertensive patients in Singapore. J Clin Endocrinol Metab. 2000; 85(8):2854-9. DOI: 10.1210/jcem.85.8.6752. View

Mosso L, Carvajal C, Gonzalez A, Barraza A, Avila F, Montero J . Primary aldosteronism and hypertensive disease. Hypertension. 2003; 42(2):161-5. DOI: 10.1161/01.HYP.0000079505.25750.11. View

Milliez P, Girerd X, Plouin P, Blacher J, Safar M, Mourad J . Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005; 45(8):1243-8. DOI: 10.1016/j.jacc.2005.01.015. View

Savard S, Amar L, Plouin P, Steichen O . Cardiovascular complications associated with primary aldosteronism: a controlled cross-sectional study. Hypertension. 2013; 62(2):331-6. DOI: 10.1161/HYPERTENSIONAHA.113.01060. View

Choi M, Scholl U, Yue P, Bjorklund P, Zhao B, Nelson-Williams C . K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. Science. 2011; 331(6018):768-72. PMC: 3371087. DOI: 10.1126/science.1198785. View

Beuschlein F, Boulkroun S, Osswald A, Wieland T, Nielsen H, Lichtenauer U . Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. Nat Genet. 2013; 45(4):440-4, 444e1-2. DOI: 10.1038/ng.2550. View

Azizan E, Poulsen H, Tuluc P, Zhou J, Clausen M, Lieb A . Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension. Nat Genet. 2013; 45(9):1055-60. DOI: 10.1038/ng.2716. View

Scholl U, Stolting G, Nelson-Williams C, Vichot A, Choi M, Loring E . Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism. Elife. 2015; 4:e06315. PMC: 4408447. DOI: 10.7554/eLife.06315. View

Fernandes-Rosa F, Daniil G, Orozco I, Goppner C, El Zein R, Jain V . A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism. Nat Genet. 2018; 50(3):355-361. DOI: 10.1038/s41588-018-0053-8. View

10.

Nanba K, Omata K, Else T, Beck P, Nanba A, Turcu A . Targeted Molecular Characterization of Aldosterone-Producing Adenomas in White Americans. J Clin Endocrinol Metab. 2018; 103(10):3869-3876. PMC: 6179168. DOI: 10.1210/jc.2018-01004. View

11.

Taguchi R, Yamada M, Nakajima Y, Satoh T, Hashimoto K, Shibusawa N . Expression and mutations of KCNJ5 mRNA in Japanese patients with aldosterone-producing adenomas. J Clin Endocrinol Metab. 2012; 97(4):1311-9. DOI: 10.1210/jc.2011-2885. View

12.

Zheng F, Zhu L, Nie A, Li X, Lin J, Zhang K . Clinical characteristics of somatic mutations in Chinese patients with aldosterone-producing adenoma. Hypertension. 2015; 65(3):622-8. DOI: 10.1161/HYPERTENSIONAHA.114.03346. View

13.

Lenzini L, Rossitto G, Maiolino G, Letizia C, Funder J, Rossi G . A Meta-Analysis of Somatic KCNJ5 K(+) Channel Mutations In 1636 Patients With an Aldosterone-Producing Adenoma. J Clin Endocrinol Metab. 2015; 100(8):E1089-95. DOI: 10.1210/jc.2015-2149. View

14.

Vilela L, Rassi-Cruz M, Guimaraes A, Moises C, Freitas T, Alencar N . KCNJ5 Somatic Mutation Is a Predictor of Hypertension Remission After Adrenalectomy for Unilateral Primary Aldosteronism. J Clin Endocrinol Metab. 2019; 104(10):4695-4702. DOI: 10.1210/jc.2019-00531. View

15.

Ross R . Atherosclerosis--an inflammatory disease. N Engl J Med. 1999; 340(2):115-26. DOI: 10.1056/NEJM199901143400207. View

16.

Higashi Y, Noma K, Yoshizumi M, Kihara Y . Endothelial function and oxidative stress in cardiovascular diseases. Circ J. 2009; 73(3):411-8. DOI: 10.1253/circj.cj-08-1102. View

17.

Celermajer D, Sorensen K, Gooch V, Spiegelhalter D, Miller O, Sullivan I . Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992; 340(8828):1111-5. DOI: 10.1016/0140-6736(92)93147-f. View

18.

Corretti M, Anderson T, Benjamin E, Celermajer D, Charbonneau F, Creager M . Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002; 39(2):257-65. DOI: 10.1016/s0735-1097(01)01746-6. View

19.

Nishizaka M, Zaman M, Green S, Renfroe K, Calhoun D . Impaired endothelium-dependent flow-mediated vasodilation in hypertensive subjects with hyperaldosteronism. Circulation. 2004; 109(23):2857-61. DOI: 10.1161/01.CIR.0000129307.26791.8E. View

20.

Duffy S, Biegelsen E, Eberhardt R, Kahn D, Kingwell B, Vita J . Low-renin hypertension with relative aldosterone excess is associated with impaired NO-mediated vasodilation. Hypertension. 2005; 46(4):707-13. PMC: 2737344. DOI: 10.1161/01.HYP.0000184231.84465.62. View