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Updated: Apr 6, 2026

High-throughput Screening for Small-molecule Modulators of Inward Rectifier Potassium Channels
Published on: January 27, 2013
Novel Agents for the Prevention and Management of Hyperkalemia
Peter A McCullough, Maria Rosa Costanzo, Marc Silver
1Baylor University Medical Center, Baylor Heart and Vascular Institute, Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, TX, and The Heart Hospital, Plano, TX; Advocate Heart Institute, and Edward Heart Hospital, Naperville, IL; Advocate Christ Medical Center, Oak Lawn, IL; Division of Nephrology, New York Hospital Queens, and Nephrology Associates, Flushing, NY; David Geffen School of Medicine at UCLA and Cedars-Sinai Medical Center, Los Angeles, CA, and Westside Medical Associates of Los Angeles, Beverly Hills, CA.
Insights
Hyperkalemia, or high potassium, is increasingly common. New oral therapies like patiromer and sodium zirconium cyclosilicate offer novel ways to manage this condition in cardiorenal disease.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Hyperkalemia (serum potassium > 5.0 mEq/L) is rising in cardiovascular practice.
- Increased prevalence linked to chronic kidney disease and use of RAAS inhibitors and MRA therapies.
- Hyperkalemia risk limits use of essential cardiorenal disease-modifying drugs.
Purpose of the Study:
- Review mechanisms of hyperkalemia.
- Highlight novel oral therapies for hyperkalemia management.
- Discuss clinical trial results of new potassium-binding agents.
Main Methods:
- Review of existing literature on hyperkalemia.
- Analysis of randomized trials for novel oral therapies.
- Comparison of patiromer sorbitex calcium and sodium zirconium cyclosilicate.
Main Results:
- Patiromer and sodium zirconium cyclosilicate are novel oral therapies for hyperkalemia.
- These agents have distinct biochemical profiles and clinical outcomes.
- Clinical trials demonstrate efficacy in various cardiorenal scenarios.
Conclusions:
- Effective hyperkalemia management is crucial for cardiorenal disease treatment.
- Novel oral agents provide new options for controlling serum potassium.
- Understanding biochemical differences is key to selecting appropriate therapy.
Abstract:
Hyperkalemia is defined as serum potassium concentrations elevated above the upper limit of normal (> 5.0 mEq/L). It has become more common in cardiovascular practice due to the growing population of patients with chronic kidney disease and the broad application of drugs that modulate renal elimination of potassium by reducing production of angiotensin II (angiotensin-converting enzyme inhibitors, direct renin inhibitors, β-adrenergic receptor antagonists), blocking angiotensin II receptors (angiotensin receptor blockers), or antagonizing the action of aldosterone on mineralocorticoid receptors (mineralocorticoid receptor antagonists). The risk of hyperkalemia is a major limiting factor for the use of these disease-modifying drugs in both acute and chronic cardiorenal syndromes. Thus, agents to control the plasma concentration of potassium are needed in the multidrug treatment of cardiorenal disease, including chronic kidney disease, heart failure, and acute kidney injury. Novel oral therapies in development for both acute and extended use in the management of hyperkalemia include patiromer sorbitex calcium and sodium zirconium cyclosilicate. Important biochemical differences between these compounds result in unique product profiles and electrolyte outcomes in patients treated for hyperkalemia. This review highlights the major mechanisms of hyperkalemia and key results from randomized trials in a range of clinical scenarios in patients with, and at risk for, hyperkalemia.
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