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. 2025 Feb;42(2):135-142.
doi: 10.1007/s40266-024-01171-4. Epub 2025 Jan 8.

Exploring Hyperkalemia Risk in Frail Older Patients Using RAAS Inhibitors

Anna M J Heemels  1 , Nadine P P M Gadiot  2 , Angele P M Kerckhoffs  1 , Namiko A Goto  1
Affiliations

Exploring Hyperkalemia Risk in Frail Older Patients Using RAAS Inhibitors

Anna M J Heemels et al. Drugs Aging. 2025 Feb.

Abstract

Purpose: Renin-angiotensin-aldosterone system inhibitors (RAASi) are widely used in treatment of cardiovascular and renal disease. While effective, they pose a risk of hyperkalemia. In the general population, risk factors for hyperkalemia include chronic kidney disease, congestive heart failure, and use of medication affecting potassium balance. These risk factors are prevalent in frail older patients. Therefore, this study aims to explore the prevalence and risk factors for hyperkalemia associated with RAASi use in this vulnerable population.

Patients and methods: This single-center, cross-sectional study included RAASi users aged ≥ 70 years who presented at the emergency department. Clinical Frailty Scale (CFS) according to Rockwood was calculated retrospectively from information in clinical files. All patients with CFS ≥ 5 were considered frail. Hyperkalemia was defined as serum potassium ≥ 5.5 mmol/L at time of presentation at the emergency department. Potential risk factors for hyperkalemia in older patients were identified using logistic regression models.

Results: Of the 2023 participants, 86 (4.3%) were hyperkalemic, with no significant difference between frail and non-frail patients (4.7% versus 3.3%, p-value 0.157). Hyperkalemic patients were slightly younger than non-hyperkalemic patients (median age 83 versus 84 years, p-value 0.023), and females were slightly overrepresented in both groups (52.6% and 53.5%, p = 0.867). Risk factors associated with hyperkalemia in older RAASi users included younger age (odds ratio (OR) 0.95, 95% confidence intervals (CI) 0.92-0.99, p = 0.010), diabetes mellitus (OR 1.67, 95% CI 1.05-2.65, p = 0.030), moderate to severe kidney failure (OR 9.87, 95% CI 6.01-16.21, p < 0.001), and use of potassium-binding agents (OR 14.62, 95% CI 1.56-137.40, p = 0.019) and potassium-sparing diuretics (OR 2.66, 95% CI 1.57-4.50, p < 0.001).

Conclusions: Contrary to expectations, this study found no association between frailty and hyperkalemia in older RAASi users visiting the emergency department. These results suggest that frail older patients without additional risk factors can be treated with RAASi when indicated, similar to the general population. The main risk factors for hyperkalemia in this population remain consistent with those in the general population, emphasizing the importance of monitoring kidney function and medication use.

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Conflict of interest statement

Declarations. Funding: No external funding was used in the preparation of this manuscript. Conflict of interest: Annemieke Heemels, Nadine Gadiot, Angele Kerckhoffs, and Namiko Goto declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript. Authors’ contributions: All authors contributed to the study conception and design. Data collection was performed by A. Heemels and N. Gadiot. Analysis was performed by A. Heemels. The first draft of the manuscript was written by A. Heemels, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the ethics committee of Jeroen Bosch Hospital (approval no. nw2022-19). Code availability: Not applicable. Consent to participate: Not applicable since for this study only pooled anonymized data were used. Patients who have previously objected to their information being used for scientific research, by the hospital opt-out procedure, were not included. Consent for publication: Not applicable.

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