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Disease State Overview: Hyperkalemia, A Serious Condition With Limited Treatments

Disease State Overview: Hyperkalemia, A Serious Condition With Limited Treatments

Managing hyperkalemia is complex and current options are limited; new therapies may address treatment gap.

Hyperkalemia, or high serum potassium, is a potentially life-threatening situation in which the serum potassium level surpasses >5.0 mEq/L.1 This can result in serious clinical com­plications in both acute and chronic care settings. Individuals at highest risk for hyperkalemia include those with stage 3 or stage 4 chronic kidney disease (CKD) and/or those with heart failure and underly­ing comorbidities.2,3 Managing hyperkalemia is a challenge because current treatment options are limited, underscoring an unmet need for therapies that address hyperkalemia.


Hyperkalemia can be classified according to serum potassium into mild (5.5-6.5 mEq/L), mod­erate (6.5-7.5 mEq/L), and severe (>7.5 mEq/L). Greater degrees of hyperkalemia may lead to cardiac arrhythmias and cardiac arrest, with increased mortality.2,4 Reasons for elevated potassium levels in patients with CKD include increased potassium intake, altered potassium handling by the kidneys, aldosterone resis­tance, and lack of insulin.2 Some medications frequently prescribed to individuals with CKD and heart failure may compound the hyper­kalemia risk such as nonsteroidal anti-inflammatory drugs and beta-blockers. Renin–angiotensin–aldo­sterone system (RAAS) inhibitors are one well-documented class of drugs that can cause hyperkalemia (eg, angiotensin-converting enzyme inhibitors and angiotensin recep­tor blockers).1,2,4-6 Further, there is greater risk of drug–drug interactions (DDIs) when patients are taking com­binations of potassium-increasing drugs.5

 Hyperkalemia symptoms are non­specific and predominately related to cardiac or neuromuscular dysfunc­tion.1 Diagnosis of hyperkalemia may be made with identification of elevated laboratory serum potassium levels, and reinforced through physical assessment findings, patient history, and medication review.

 Assessment of cardiac function, kidneys, and uri­nary tract, as well as hydration status and neuro­logical evaluation, should be performed. Additional blood testing should be ordered as appropriate to facilitate the differential diagnosis for the cause. An electrocardiogram (ECG) should be performed to help confirm any cardiac changes related to hyper-kalemia. If an elevated serum potassium is identified in an asymptomatic patient with no apparent cause, care should be given to rule out the possibility of pseudohyperkalemia.1,4



Treatment for hyperkalemia centers on lower­ing potassium levels, preventing recurrences, and monitoring for patient safety. Therapeutic strategies should be individualized, taking into account the severity and cause of hyperkalemia. Management should not only rely on the ECG changes but also guided by the clinical scenario and serum potassium measurements. Appropriate treatment is determined by the speed of onset, severity level, and development of clinical findings.1,4

 However, the armamentarium for treatment of hyperkalemia is limit­ed. Options for the management of hyperkalemia include discontinuation or reduced doses of RAAS inhibitors, loop diuretics, restriction of dietary potassium, or sodium polystyrene sulfonate. The challenge for clinicians is that none of these approaches are optimal because they require with­holding life-saving or kidney preserv­ing therapy, have a low rate of patient adherence (eg, dietary restriction), or have an unfavorable adverse effect profile and low tolerability.6


 Two oral agents—patiromer and sodium zirconium cyclosilicate (ZS- 9)—may offer clinicians new treat­ment options for patients with the hyperkalemia. Patiromer was recently approved by the US Food and Drug Administra­tion, and ZS-9 is currently under review. Clinical trials have shown both agents are effective and well-tolerated in reducing serum potassium levels.6


 A 2-part, single-blind, phase 3 study evaluating the safety of patiromer for the treatment of hyper­kalemia showed patiromer decreased potassium levels in hyperkalemic CKD patients taking RAAS inhibitors. At 4 weeks, 76% of patients had potas­sium levels in the target range (3.8 to <5.1 mEq/L).7 Studies have assessed the safety and efficacy of ZS-9 in a variety of diagnoses associated with hyperkalemia and found the drug was effective in reducing potassium levels.6

Hyperkalemia is a complex medical issue with the potential to develop multisystem complications for patients with CKD, heart failure, or other comor­bidities.1,6 Rapid identification and treatment are critical to prevent the development of potentially fatal cardiac dysrhythmias.1

Additionally, systematic measuring of serum potassium levels before therapies involving potassium-increasing DDIs are prescribed and periodic monitoring are crucial for reducing the risk of hyperkalemia.5—Eileen Koutnik-Fotopoulos



1. Crawford AH. Hyperkalemia: recognition and management of a crucial electrolyte disturbance. J Infus Nurs. 2014;37(3);167-175.

2. Ingelfinger JR. A new era for the treatment of hyperkalemia? N Engl J Med. 2015;372(3):275-277.

3. Afzal B, Mehmood A, Shahbaz S, Kabir S, Zai TK. Predictors of outcome in patients presenting with moderate to severe hyperkalemia. Emergency Med. 2013;4(1):169.

4. Lenhardt A, Kemper MJ. Pathogenesis, diagno­sis and management of hyperkalemia. Pediatr Nephrol. 2011;26(3):377-384.

5. Eschmann E, Beeler PE, Kaplan V, et al. Patient-and physician-related risk factors for hyperkale­mia in potassium-increasing drug–drug interac­tions. Eur J Clin Pharmacol. 2014;70(2);215-223.

6. Pitt B, Bakris GL. New potassium binders for the treatment of hyperkalemia: Current data and opportunities for the future. Hypertension. 2015;66(4):731-728.

7. Weir MR, Bakris GL, Bushinsky DA, et al. Patiromer in patients with kidney disease and hyperka­lemia receiving RAAS inhibitors. N Eng J Med. 2015;372(3):211-221.

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