Estimated Effect of Restarting Renin-Angiotensin System Inhibitors after Discontinuation on Kidney Outcomes and Mortality

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

doi:https://doi.org/10.1681/ASN.0000000000000425

Estimated Effect of Restarting Renin-Angiotensin System Inhibitors after Discontinuation on Kidney Outcomes and Mortality

Hattori, Koki; Sakaguchi, Yusuke; Oka, Tatsufumi et al.

Journal of the American Society of Nephrology, 2024, 35(10), 1391-1401

Number of Access:2,258（2025-10-24 11:55 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/97749

Link to primary information

File	Format	Terms of use	Size	Views	Date.Available	Description	information
JAmSocNephrol_0425	pdf	None	604 KB	154	2025.06.18

Item Information

Output File Export EndNote Basic Export Mendeley

Title	Estimated Effect of Restarting Renin-Angiotensin System Inhibitors after Discontinuation on Kidney Outcomes and Mortality
Creator	CreatorName Hattori, Koki
	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
	NRID 1000010795173 1000010795173 CreatorName Oka, Tatsufumi
	NRID 1000090869934 1000090869934 researchmap permalink y_asahina y_asahina CreatorName Asahina, Yuta
	CreatorName Kawaoka, Takayuki
	NRID 1000030846382 1000030846382 ORCID 0000-0002-5165-291X 0000-0002-5165-291X researchmap permalink DOI-YOHEI DOI-YOHEI CreatorName Doi, Yohei
	NRID 1000050791589 1000050791589 CreatorName Hashimoto, Nobuhiro
	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 57791172700 57791172700 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 researchmap permalink isaka-handai3857 isaka-handai3857 Scopus Author ID 16207611100 16207611100 ORCID 0000-0002-0820-7167 0000-0002-0820-7167 CreatorName Isaka, Yoshitaka
Subject	ACE inhibitors
	CKD
	ESKD
Description	Hattori K., Sakaguchi Y., Oka T., et al. Estimated Effect of Restarting Renin-Angiotensin System Inhibitors after Discontinuation on Kidney Outcomes and Mortality. Journal of the American Society of Nephrology, (2024); https://doi.org/10.1681/ASN.0000000000000425.
Abstract	Key points: Restarting renin-angiotensin system inhibitor after discontinuation was associated with a lower risk of kidney outcomes and mortality but not related to hyperkalemia.Our findings support a proactive approach to restarting renin-angiotensin system inhibitor among patients with CKD. Background: While renin-angiotensin system inhibitors (RASi) have been the mainstream treatment for patients with CKD, they are often discontinued because of adverse effects such as hyperkalemia and AKI. It is unknown whether restarting RASi after discontinuation improves clinical outcomes. Methods: Using the Osaka Consortium for Kidney disease Research database, we performed a target trial emulation study including 6065 patients with an eGFR of 10-60 ml/min per 1.73 m² who were followed up by nephrologists and discontinued RASi between 2005 and 2021. With a clone-censor-weight approach, we compared a treatment strategy for restarting RASi within a year after discontinuation with that for not restarting RASi. Patients were followed up for 5 years at maximum after RASi discontinuation. The primary outcome was a composite kidney outcome (initiation of KRT, a ≥50% decline in eGFR, or kidney failure [eGFR <5 ml/min per 1.73 m²]). Secondary outcomes were all-cause death and incidence of hyperkalemia (serum potassium levels ≥5.5 mEq/L). Results: Among those who discontinued RASi (mean [SD] age 66 [15] years, 62% male, mean [SD] eGFR 40 [26] ml/min per 1.73 m²), 2262 (37%) restarted RASi within a year. Restarting RASi was associated with a lower hazard of the composite kidney outcome (hazard ratio [HR], 0.85; 95% confidence intervals [CIs], 0.78 to 0.93]) and all-cause death (HR, 0.70; 95% CI, 0.61 to 0.80) compared with not restarting RASi. The incidence of hyperkalemia did not differ significantly between the two strategies (HR, 1.11; 95% CI, 0.96 to 1.27). Conclusions: Restarting RASi after discontinuation was associated with a lower risk of kidney outcomes and mortality but not related to the incidence of hyperkalemia.
Publisher	Wolters Kluwer Health
Source Title	Journal of the American Society of Nephrology
Volume (Issue)	35(10)
Page	1391-1401
Date of Issued	2024-06-18
Language	English
Handle URL	https://hdl.handle.net/11094/97749
PISSN	10466673
eISSN	15333450
Relation.isVersionOf	DOI (Publisher Version) https://doi.org/10.1681/ASN.0000000000000425
Access Rights	open access
oaire:version	Accepted Manuscript
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Journal of the American Society of Nephrology. 2024, 35(10), p. 1391-1401
DC.title	Estimated Effect of Restarting Renin-Angiotensin System Inhibitors after Discontinuation on Kidney Outcomes and Mortality
DC.creator	Hattori, Koki
	Sakaguchi, Yusuke
	Oka, Tatsufumi
	Asahina, Yuta
	Kawaoka, Takayuki
	Doi, Yohei
	Hashimoto, Nobuhiro
	Kusunoki, Yasuo
	Yamamoto, Satoko
	Yamato, Masafumi
	Yamamoto, Ryohei
	Matsui, Isao
	Mizui, Masayuki
	Kaimori, Jun-Ya
	Isaka, Yoshitaka
DC.publisher	Wolters Kluwer Health
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-06-18
DC.identifier	https://doi.org/10.1681/ASN.0000000000000425
DC.subject	ACE inhibitors
	CKD
	ESKD
DC.description	Hattori K., Sakaguchi Y., Oka T., et al. Estimated Effect of Restarting Renin-Angiotensin System Inhibitors after Discontinuation on Kidney Outcomes and Mortality. Journal of the American Society of Nephrology, (2024); https://doi.org/10.1681/ASN.0000000000000425.
DCTERMS.abstract	Key points: Restarting renin-angiotensin system inhibitor after discontinuation was associated with a lower risk of kidney outcomes and mortality but not related to hyperkalemia.Our findings support a proactive approach to restarting renin-angiotensin system inhibitor among patients with CKD. Background: While renin-angiotensin system inhibitors (RASi) have been the mainstream treatment for patients with CKD, they are often discontinued because of adverse effects such as hyperkalemia and AKI. It is unknown whether restarting RASi after discontinuation improves clinical outcomes. Methods: Using the Osaka Consortium for Kidney disease Research database, we performed a target trial emulation study including 6065 patients with an eGFR of 10-60 ml/min per 1.73 m² who were followed up by nephrologists and discontinued RASi between 2005 and 2021. With a clone-censor-weight approach, we compared a treatment strategy for restarting RASi within a year after discontinuation with that for not restarting RASi. Patients were followed up for 5 years at maximum after RASi discontinuation. The primary outcome was a composite kidney outcome (initiation of KRT, a ≥50% decline in eGFR, or kidney failure [eGFR <5 ml/min per 1.73 m²]). Secondary outcomes were all-cause death and incidence of hyperkalemia (serum potassium levels ≥5.5 mEq/L). Results: Among those who discontinued RASi (mean [SD] age 66 [15] years, 62% male, mean [SD] eGFR 40 [26] ml/min per 1.73 m²), 2262 (37%) restarted RASi within a year. Restarting RASi was associated with a lower hazard of the composite kidney outcome (hazard ratio [HR], 0.85; 95% confidence intervals [CIs], 0.78 to 0.93]) and all-cause death (HR, 0.70; 95% CI, 0.61 to 0.80) compared with not restarting RASi. The incidence of hyperkalemia did not differ significantly between the two strategies (HR, 1.11; 95% CI, 0.96 to 1.27). Conclusions: Restarting RASi after discontinuation was associated with a lower risk of kidney outcomes and mortality but not related to the incidence of hyperkalemia.
DC.format	97749
citation_title	Estimated Effect of Restarting Renin-Angiotensin System Inhibitors after Discontinuation on Kidney Outcomes and Mortality
citation_author	Hattori, Koki
	Sakaguchi, Yusuke
	Oka, Tatsufumi
	Asahina, Yuta
	Kawaoka, Takayuki
	Doi, Yohei
	Hashimoto, Nobuhiro
	Kusunoki, Yasuo
	Yamamoto, Satoko
	Yamato, Masafumi
	Yamamoto, Ryohei
	Matsui, Isao
	Mizui, Masayuki
	Kaimori, Jun-Ya
	Isaka, Yoshitaka
citation_publisher	Wolters Kluwer Health
citation_language	English
citation_date	2024-06-18
citation_journal_title	Journal of the American Society of Nephrology
citation_volume	35
citation_issue	10
citation_firstpage	1391
citation_lastpage	1401
citation_doi	https://doi.org/10.1681/ASN.0000000000000425
citation_public_url	https://hdl.handle.net/11094/97749

Estimated Effect of Restarting Renin-Angiotensin System Inhibitors after Discontinuation on Kidney Outcomes and Mortality

Link to primary information

Item Information

Show details