What is hyperkalemia?

What is Hyperkalemia?

Hyperkalemia is a potentially life-threatening electrolyte disorder defined as an elevated serum potassium concentration greater than 5.0 mEq/L (mmol/L), which can cause cardiac arrhythmias, cardiac arrest, and death if untreated. 1, 2

Definition and Severity Classification

Hyperkalemia is classified by severity based on serum potassium levels: 2

• Mild hyperkalemia: >5.0 to <5.5 mEq/L
• Moderate hyperkalemia: 5.5 to 6.0 mEq/L
• Severe hyperkalemia: >6.0 mEq/L

The disorder results from the kidneys' inability to excrete potassium, impairment of mechanisms that move potassium from circulation into cells, or a combination of these factors. 3

Prevalence and At-Risk Populations

The prevalence varies significantly by clinical setting: 2

• General population: 2-4%
• Hospitalized patients: 10-55%
• Advanced chronic kidney disease: Up to 73%

Patients at highest risk include those with chronic kidney disease, heart failure, diabetes mellitus, and those receiving renin-angiotensin-aldosterone system inhibitors (RAASi). 1, 2

Pathophysiology and Clinical Consequences

Potassium homeostasis is primarily maintained by the kidneys, with the gastrointestinal tract playing a lesser role. 1 Hyperkalemia exerts depolarizing effects on the heart, causing shortened action potentials and dramatically increasing arrhythmia risk. 1

The disorder also causes: 1

• Neuromuscular symptoms (muscle weakness, paresthesias)
• Metabolic acidosis
• Suppression of ammoniagenesis

A U-shaped relationship exists between serum potassium and mortality, with both hyperkalemia and hypokalemia associated with adverse outcomes. 1 The risk of mortality, cardiovascular morbidity, CKD progression, and hospitalization increases substantially in hyperkalemic patients. 1

Common Causes

Medication-Induced (Most Important in Clinical Practice)

Drug-induced hyperkalemia represents the most important cause in everyday practice: 4

• RAASi medications: ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists 2, 4
• Potassium-sparing diuretics: Spironolactone, triamterene, amiloride 2
• Beta-blockers (reduce renin release) 2
• NSAIDs 2, 4
• Calcineurin inhibitors: Cyclosporine, tacrolimus 2
• Trimethoprim-sulfamethoxazole 2
• Heparin (suppresses aldosterone production) 2

Renal and Metabolic Causes

Reduced potassium excretion typically results from decreased potassium secretion in the aldosterone-sensitive distal nephron, commonly associated with: 5

• Kidney failure
• Limited delivery of sodium and water to the distal nephron
• Hyporeninemic hypoaldosteronism (particularly in diabetic nephropathy) 3

Clinical Presentation

Hyperkalemia is often asymptomatic, especially in chronic cases, making laboratory and ECG monitoring essential. 2 When symptoms occur, they may include: 2

• Muscle weakness
• Paresthesias
• Cardiac arrhythmias

ECG Changes: Critical Warning Signs

ECG changes may be the first indicator of hyperkalemia before symptoms appear, and their presence indicates severe cardiotoxicity requiring immediate treatment. 6 The progression follows a predictable sequence: 6

1. Peaked/tented T waves (earliest finding, usually at K+ >5.5 mmol/L)
2. Flattened or absent P waves, prolonged PR interval, widened QRS complex
3. Severe changes (K+ >6.5 mmol/L): Merging of S and T waves, progressive QRS widening, sine-wave pattern
4. Life-threatening: Idioventricular rhythms, ventricular fibrillation, or asystolic cardiac arrest

Critical caveat: The absence of ECG changes does not rule out dangerous hyperkalemia, as not all patients develop ECG changes at the same potassium level. 6 Patients with chronic kidney disease, diabetes, or heart failure may tolerate higher levels without ECG changes due to physiologic adaptation. 6, 7

Diagnostic Approach

Always confirm hyperkalemia with laboratory testing and rule out pseudohyperkalemia before initiating treatment. 2 Pseudohyperkalemia can result from: 2

• Hemolysis during sample collection
• Excessive fist clenching during blood draw
• Delayed specimen processing

Obtain an ECG immediately to assess for cardiac effects, and review the medication list for potential causative agents. 2

Relationship Between Potassium Level and Risk

The clinical context in which hyperkalemia develops is at least as important as the degree of hyperkalemia in determining patient outcome. 7 The rate of potassium increase matters significantly—a rapid increase is more likely to cause cardiac abnormalities than a slow, steady rise over months. 1

In patients with CKD, compensatory mechanisms may result in tolerance to elevated circulating potassium, and several studies suggest hyperkalemia is less immediately threatening in this population compared to those with normal kidney function. 1