Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023;54(7-8):258-267.
doi: 10.1159/000531102. Epub 2023 May 18.

Discontinuation of Renin-Angiotensin-Aldosterone System Inhibitors Secondary to Hyperkalemia Translates into Higher Cardiorenal Outcomes

Jaejin An  1   2 , Hui Zhou  1   2 , Liang Ni  1 , Teresa N Harrision  1 , Rong Wei  1 , Abiy Agiro  3 , Yasmin Ghanshyam Brahmbhatt  3 , Yemmie Oluwatosin  3 , Craig G Schilling  3 , John J Sim  2   4
Affiliations

Discontinuation of Renin-Angiotensin-Aldosterone System Inhibitors Secondary to Hyperkalemia Translates into Higher Cardiorenal Outcomes

Jaejin An et al. Am J Nephrol. 2023.

Abstract

Introduction: Discontinuation of renin-angiotensin-aldosterone system inhibitor (RAASi) is common after hyperkalemia. We evaluated the risk of kidney and mortality outcomes associated with RAASi discontinuation among patients with chronic kidney disease (CKD) and hyperkalemia.

Methods: We identified adult patients with CKD (eGFR <60 mL/min/1.73 m2) who experienced new-onset hyperkalemia (potassium ≥5.0 mEq/L) between 2016 and 2017 from Kaiser Permanente Southern California and followed them through 2019. We defined treatment discontinuation as having ≥90-day gap in refills of all RAASi within 3 months after hyperkalemia. We used multivariable Cox proportional hazards models to evaluate the association between RAASi discontinuation and the primary composite outcome of kidney (≥40% eGFR decline, dialysis, kidney transplant) or all-cause mortality. We evaluated cardiovascular events and recurrence of hyperkalemia as secondary outcomes.

Results: Among 5,728 patients (mean age 76 years), 13.5% discontinued RAASi within 3 months after new-onset hyperkalemia. During the median 2 years of follow-up, 29.7% had the primary composite outcome (15.5% with ≥40% eGFR decline, 2.8% dialysis or kidney transplant, 18.4% all-cause mortality). Patients who discontinued RAASi had a higher all-cause mortality compared with those who continued RAASi (26.7% vs. 17.1%) but had no differences in kidney outcomes, cardiovascular events, and recurrence of hyperkalemia. RAASi discontinuation was associated with a higher risk of kidney or all-cause mortality composite outcome (adjusted hazard ratio [aHR] 1.21, 95% CI: 1.06, 1.37) mainly driven by all-cause mortality (aHR: 1.34, 95% CI: 1.14, 1.56).

Conclusion: RAASi discontinuation after hyperkalemia was associated with worsened mortality, which may underscore the benefits of continuing RAASi among patients with CKD.

Keywords: Hyperkalemia; Kidney outcome; Medication use; Mortality; Renin-angiotensin-aldosterone system inhibition.

PubMed Disclaimer

Conflict of interest statement

J.A., H.Z., J.J.S., R.W., T.N.H., and L.N. received research support from AstraZeneca, that was paid directly to KPSC, for the conduct of this study. J.A. received research support from Novartis outside scope of this study. A.A., Y.G.B., Y.O., and C.S. are employees and stockholders of AstraZeneca.

Figures

Fig. 1.
Fig. 1.
Kaplan-Meier survival curves for primary outcome (kidney or all-cause mortality) for RAASi discontinuation (vs. continuation). RAASi, renin-angiotensin-aldosterone system inhibitors.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Humphrey T, Davids MR, Chothia MY, Pecoits-Filho R, Pollock C, James G. How common is hyperkalaemia? A systematic review and meta-analysis of the prevalence and incidence of hyperkalaemia reported in observational studies. Clin Kidney J. 2022;15(4):727–37. 10.1093/ckj/sfab243. - DOI - PMC - PubMed
    1. Fitch K, Woolley JM, Engel T, Blumen H. The clinical and economic burden of hyperkalemia on medicare and commercial payers. Am Health Drug Benefits. 2017;10(4):202–10. - PMC - PubMed
    1. Weir MR, Rolfe M. Potassium homeostasis and renin-angiotensin-aldosterone system inhibitors. Clin J Am Soc Nephrol. 2010;5(3):531–48. 10.2215/CJN.07821109. - DOI - PubMed
    1. Allon M. Hyperkalemia in end-stage renal disease: mechanisms and management. J Am Soc Nephrol. 1995;6(4):1134–42. 10.1681/ASN.V641134. - DOI - PubMed
    1. Fonseca C, Brito D, Branco P, Frazão JM, Silva-Cardoso J, Bettencourt P. Hyperkalemia and management of renin-angiotensin-aldosterone system inhibitors in chronic heart failure with reduced ejection fraction: a systematic review. Rev Port Cardiol. 2020;39(9):517–41. 10.1016/j.repc.2020.03.015. - DOI - PubMed

Publication types