Discontinuing renin-angiotensin system inhibitors after incident hyperkalemia and clinical outcomes: target trial emulation

Hashimoto, Nobuhiro; Sakaguchi, Yusuke; Hattori, Koki; Kawano, Yuki; Kawaoka, Takayuki; Doi, Yohei; Oka, Tatsufumi; Kusunoki, Yasuo; Yamamoto, Satoko; Yamato, Masafumi; Yamamoto, Ryohei; Matsui, Isao; Mizui, Masayuki; Kaimori, Jun Ya; Isaka, Yoshitaka

doi:https://doi.org/10.1038/s41440-025-02218-8

Discontinuing renin-angiotensin system inhibitors after incident hyperkalemia and clinical outcomes: target trial emulation

Hashimoto, Nobuhiro; Sakaguchi, Yusuke; Hattori, Koki et al.

Hypertension Research, 2025, 48, 2034-2044

Number of Access:41（2025-08-14 04:33 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/102246

Link to primary information

File	Format	Terms of use	Size	Views	Date.Available	Description	information
HypertensRes_48_2034	pdf	None	626 KB	14	2025.07.10

Creative Commons : Attribution

Item Information

Output File Export EndNote Basic Export Mendeley

Title	Discontinuing renin-angiotensin system inhibitors after incident hyperkalemia and clinical outcomes: target trial emulation
Creator	NRID 1000050791589 1000050791589 CreatorName Hashimoto, Nobuhiro
	NRID 1000080756817 1000080756817 researchmap permalink sakaguchi-handai3857 sakaguchi-handai3857 Scopus Author ID 35183980700 35183980700 ORCID 0000-0002-0987-5423 0000-0002-0987-5423 CreatorName Sakaguchi, Yusuke
	CreatorName Hattori, Koki
	CreatorName Kawano, Yuki
	CreatorName Kawaoka, Takayuki
	NRID 1000030846382 1000030846382 ORCID 0000-0002-5165-291X 0000-0002-5165-291X researchmap permalink DOI-YOHEI DOI-YOHEI CreatorName Doi, Yohei
	CreatorName Oka, Tatsufumi
	CreatorName Kusunoki, Yasuo
	CreatorName Yamamoto, Satoko
	CreatorName Yamato, Masafumi
	NRID 1000000533853 1000000533853 ORCID 0000-0003-2610-9824 0000-0003-2610-9824 researchmap permalink yamamotor yamamotor Scopus Author ID 13104281900 13104281900 CreatorName Yamamoto, Ryohei
	NRID 1000060456986 1000060456986 ORCID 0000-0001-8378-6130 0000-0001-8378-6130 researchmap permalink matsui-handai3857 matsui-handai3857 Scopus Author ID 24488796300 24488796300 CreatorName Matsui, Isao
	NRID 1000030423106 1000030423106 ORCID 0000-0003-2543-8108 0000-0003-2543-8108 researchmap permalink msmizui msmizui Scopus Author ID 8935909200 8935909200 CreatorName Mizui, Masayuki
	NRID 1000070527697 1000070527697 CreatorName Kaimori, Jun Ya
	NRID 1000000379166 1000000379166 ORCID 0000-0002-0820-7167 0000-0002-0820-7167 researchmap permalink isaka-handai3857 isaka-handai3857 Scopus Author ID 16207611100 16207611100 CreatorName Isaka, Yoshitaka
Subject	Chronic kidney disease
	Discontinuing renin-angiotensin system inhibitors
	Hyperkalemia
	Implemental hypertension
	Kidney outcome
Description	Hashimoto N., Sakaguchi Y., Hattori K., et al. Discontinuing renin-angiotensin system inhibitors after incident hyperkalemia and clinical outcomes: target trial emulation. Hypertension Research, 48, 2034 (2025); https://doi.org/10.1038/s41440-025-02218-8.
Abstract	Although renin-angiotensin system inhibitors (RASi) are the mainstay in the management of heart failure with reduced ejection fraction, chronic kidney disease, and other cardiovascular conditions, they are often discontinued due to hyperkalemia. The prognostic impact of discontinuing RASi after developing hyperkalemia remains uncertain. Using a target trial framework based on the cloning, censoring, and weighting method, we compared discontinuing RASi after incident hyperkalemia with continuing RASi. We identified 2305 patients with an estimated glomerular filtration rate (eGFR) of ≥10 ml/min/1.73 m² who developed hyperkalemia (serum potassium levels ≥5.5 mEq/L) while on RASi in the Osaka Consortium for Kidney Disease Research (OCKR) database. The primary outcome was a composite of initiation of kidney replacement therapy, a ≥50% decline in eGFR, or reaching eGFR <5 ml/min/1.73 m². Secondary outcomes included all-cause death and severe hyperkalemia (serum potassium levels ≥6.5 mEq/L). The mean (standard deviation) age and eGFR were 68 (14) years and 29 (17) mL/min/1.73 m², respectively. After developing hyperkalemia, 346 (15%) discontinued RASi. Discontinuing RASi was associated with a 16% [95% confidence interval 2–33%] higher hazard of mortality than continuing RASi while the composite kidney outcome did not differ between groups (adjusted hazard ratio [HR] 1.01 [0.81–1.26]). Severe hyperkalemia occurred less frequently in those who discontinued RASi than those who continued RASi (adjusted HR 0.83 [0.69, 0.99]). RASi discontinuation after incident hyperkalemia was associated with higher mortality despite a lower risk of severe hyperkalemia. It was not related to kidney outcome. Appropriate clinical decision-making regarding RASi discontinuation may depend on the clinical context. (Figure presented.)
Publisher	Springer Nature
Source Title	Hypertension Research
Volume (Issue)	48
Page	2034-2044
Date of Issued	2025-05-14
Language	English
Handle URL	https://hdl.handle.net/11094/102246
PISSN	09169636
eISSN	13484214
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41440-025-02218-8
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Hypertension Research. 2025, 48, p. 2034-2044
DC.title	Discontinuing renin-angiotensin system inhibitors after incident hyperkalemia and clinical outcomes: target trial emulation
DC.creator	Hashimoto, Nobuhiro
	Sakaguchi, Yusuke
	Hattori, Koki
	Kawano, Yuki
	Kawaoka, Takayuki
	Doi, Yohei
	Oka, Tatsufumi
	Kusunoki, Yasuo
	Yamamoto, Satoko
	Yamato, Masafumi
	Yamamoto, Ryohei
	Matsui, Isao
	Mizui, Masayuki
	Kaimori, Jun Ya
	Isaka, Yoshitaka
DC.publisher	Springer Nature
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-05-14
DC.identifier	https://doi.org/10.1038/s41440-025-02218-8
DC.subject	Chronic kidney disease
	Discontinuing renin-angiotensin system inhibitors
	Hyperkalemia
	Implemental hypertension
	Kidney outcome
DC.description	Hashimoto N., Sakaguchi Y., Hattori K., et al. Discontinuing renin-angiotensin system inhibitors after incident hyperkalemia and clinical outcomes: target trial emulation. Hypertension Research, 48, 2034 (2025); https://doi.org/10.1038/s41440-025-02218-8.
DCTERMS.abstract	Although renin-angiotensin system inhibitors (RASi) are the mainstay in the management of heart failure with reduced ejection fraction, chronic kidney disease, and other cardiovascular conditions, they are often discontinued due to hyperkalemia. The prognostic impact of discontinuing RASi after developing hyperkalemia remains uncertain. Using a target trial framework based on the cloning, censoring, and weighting method, we compared discontinuing RASi after incident hyperkalemia with continuing RASi. We identified 2305 patients with an estimated glomerular filtration rate (eGFR) of ≥10 ml/min/1.73 m² who developed hyperkalemia (serum potassium levels ≥5.5 mEq/L) while on RASi in the Osaka Consortium for Kidney Disease Research (OCKR) database. The primary outcome was a composite of initiation of kidney replacement therapy, a ≥50% decline in eGFR, or reaching eGFR <5 ml/min/1.73 m². Secondary outcomes included all-cause death and severe hyperkalemia (serum potassium levels ≥6.5 mEq/L). The mean (standard deviation) age and eGFR were 68 (14) years and 29 (17) mL/min/1.73 m², respectively. After developing hyperkalemia, 346 (15%) discontinued RASi. Discontinuing RASi was associated with a 16% [95% confidence interval 2–33%] higher hazard of mortality than continuing RASi while the composite kidney outcome did not differ between groups (adjusted hazard ratio [HR] 1.01 [0.81–1.26]). Severe hyperkalemia occurred less frequently in those who discontinued RASi than those who continued RASi (adjusted HR 0.83 [0.69, 0.99]). RASi discontinuation after incident hyperkalemia was associated with higher mortality despite a lower risk of severe hyperkalemia. It was not related to kidney outcome. Appropriate clinical decision-making regarding RASi discontinuation may depend on the clinical context. (Figure presented.)
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	102246
citation_title	Discontinuing renin-angiotensin system inhibitors after incident hyperkalemia and clinical outcomes: target trial emulation
citation_author	Hashimoto, Nobuhiro
	Sakaguchi, Yusuke
	Hattori, Koki
	Kawano, Yuki
	Kawaoka, Takayuki
	Doi, Yohei
	Oka, Tatsufumi
	Kusunoki, Yasuo
	Yamamoto, Satoko
	Yamato, Masafumi
	Yamamoto, Ryohei
	Matsui, Isao
	Mizui, Masayuki
	Kaimori, Jun Ya
	Isaka, Yoshitaka
citation_publisher	Springer Nature
citation_language	English
citation_date	2025-05-14
citation_journal_title	Hypertension Research
citation_volume	48
citation_firstpage	2034
citation_lastpage	2044
citation_doi	https://doi.org/10.1038/s41440-025-02218-8
citation_public_url	https://hdl.handle.net/11094/102246

Discontinuing renin-angiotensin system inhibitors after incident hyperkalemia and clinical outcomes: target trial emulation

Link to primary information

Item Information

Show details