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New Therapeutic Approaches for the Treatment of Hyperkalemia in Patients Treated with Renin-Angiotensin-Aldosterone System Inhibitors

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Abstract

Hyperkalemia (serum potassium > 5.5 mEq/L) is a common clinical problem in patients with chronic kidney disease, hypertension, diabetes, and heart failure. It can result from increased K+ intake, impaired distribution between intracellular and extracellular spaces, and most frequently, decreased renal excretion. Patients at the highest risk of hyperkalemia are treated with renin-angiotensin-aldosterone system inhibitors (RAASIs) as they improve cardiovascular and renal outcomes and are strongly recommended in clinical guidelines. However, RAASIs cause or increase the risk of hyperkalemia, a key limitation to fully titrate RAASIs in patients who are most likely to benefit from treatment. Until recently, drugs for the treatment of hyperkalemia presented limited efficacy and/or safety concerns and there was an unmet need of new drugs to control hyperkalemia while maintaining RAASI therapy. We provide an overview of the mechanisms involved in K+ homeostasis and the epidemiology and management of hyperkalemia as a complication in cardiovascular patients and, finally, analyze the efficacy and safety of two new polymer-based, non-systemic agents, patiromer calcium and sodium zirconium cyclosilicate (ZS-9), designed to increase fecal K+ loss and to normalize elevated serum K+ levels and chronically maintain K+ homeostasis in hyperkalemic patients treated with RAASIs.

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Abbreviations

ACEIs:

Angiotensin-converting enzyme inhibitors

AEs:

Adverse events

ARBs:

Angiotensin receptor blockers

CKD:

Chronic kidney disease

eGFR:

Estimated glomerular filtration rate

HF:

Heart failure

K+ :

Potassium ions

MRAs:

Mineralocorticoid receptor antagonists

s-K+ :

Serum K+

RAASIs:

Renin-angiotensin-aldosterone system inhibitors

ZS-9:

Sodium zirconium cyclosilicate

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Acknowledgements

We thank P. Vaquero for her invaluable technical assistance.

Funding

This work was supported by the European Regional Development Fund (FEDER) and grants from the Institute of Health Carlos III (PI16/00398 and CB16/11/00303), the Ministerio de Economía y Competitividad (SAF2017-88116-P), and the BBVA Foundation.

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  1. Department of Pharmacology, School of Medicine, Instituto de Investigación Sanitaria Gregorio Marañón, CIBERCV, Universidad Complutense, 28040, Madrid, Spain

    Juan Tamargo, Ricardo Caballero & Eva Delpón

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  1. Juan Tamargo
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  2. Ricardo Caballero
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Correspondence to Juan Tamargo.

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Tamargo, J., Caballero, R. & Delpón, E. New Therapeutic Approaches for the Treatment of Hyperkalemia in Patients Treated with Renin-Angiotensin-Aldosterone System Inhibitors. Cardiovasc Drugs Ther 32, 99–119 (2018). https://doi.org/10.1007/s10557-017-6767-5

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