What is hyperkalemia?

What is Hyperkalemia

Hyperkalemia is an elevated serum potassium concentration defined as greater than 5.0 mEq/L (mmol/L), representing a potentially life-threatening electrolyte abnormality that increases the risk of fatal cardiac arrhythmias. 1, 2

Definition and Classification

Hyperkalemia severity is classified into three categories that guide treatment urgency 2, 3:

• Mild hyperkalemia: >5.0 to <5.5 mEq/L 2
• Moderate hyperkalemia: 5.5 to 6.0 mEq/L 2
• Severe hyperkalemia: >6.0 mEq/L 2

The European Society of Cardiology uses a slightly different classification system: mild (5.0-5.9 mEq/L), moderate (6.0-6.4 mEq/L), or severe (≥6.5 mEq/L) 3

Pathophysiology and Mechanisms

Hyperkalemia develops through three primary mechanisms 3:

• Impaired renal potassium excretion (the dominant cause of sustained hyperkalemia) 1, 3
• Transcellular shift of potassium from intracellular to extracellular space 3
• Excessive potassium intake in the setting of impaired renal function 3

The kidneys are the primary regulators of potassium homeostasis, and reduced potassium excretion typically occurs due to decreased potassium secretion in the aldosterone-sensitive distal nephron 1, 4

Cardiac Effects and Clinical Significance

Hyperkalemia has depolarizing effects on the heart, causing shortened action potentials and dramatically increasing the risk of fatal arrhythmias. 1, 3

The relationship between potassium levels and mortality follows a U-shaped curve, with both hyperkalemia and hypokalemia associated with adverse clinical outcomes 1, 3. However, the rate of potassium increase matters significantly—a rapid rise poses greater cardiac risk than a slow, steady elevation over months 2

High-Risk Populations

The risk of developing hyperkalemia is substantially increased in patients with 1, 3, 5:

• Chronic kidney disease (CKD) 1, 3
• Heart failure 1, 3
• Diabetes mellitus 1, 3
• Advanced age 5
• Patients receiving renin-angiotensin-aldosterone system inhibitors (RAASis) 1, 5

The prevalence of hyperkalemia is approximately 2-4% in the general population but increases to 10-55% in hospitalized patients and up to 73% in those with advanced chronic kidney disease 5

Clinical Presentation

Hyperkalemia is often asymptomatic, particularly in chronic cases 3, 5. When symptoms occur, they may include 3, 5, 4:

• Muscle weakness 3, 5
• Paresthesias 3, 5
• Nonspecific symptoms that make clinical diagnosis challenging 3

Electrocardiographic Changes

ECG changes indicate urgent treatment regardless of the absolute potassium level 2, 3. Characteristic findings include 2, 3, 5:

• Peaked T waves 2, 3, 5
• Flattened P waves 2, 3, 5
• Prolonged PR interval 2, 3, 5
• Widened QRS complex 2, 3, 5

A critical pitfall is that ECG findings can be highly variable and less sensitive than laboratory tests, so normal ECG does not exclude dangerous hyperkalemia. 3

Common Causes

Medication-Induced (Iatrogenic) Hyperkalemia

The most important cause of elevated potassium levels in everyday clinical practice is drug-induced hyperkalemia 5, 6. Common culprit medications include 5, 6:

• RAAS inhibitors: ACE inhibitors, ARBs, mineralocorticoid receptor antagonists 5, 6
• Potassium-sparing diuretics: spironolactone, triamterene, amiloride 5, 6
• NSAIDs 5, 6
• Beta-blockers 5, 6
• Trimethoprim-sulfamethoxazole 5, 6
• Heparin (suppresses aldosterone production) 5, 6
• Calcineurin inhibitors: cyclosporine, tacrolimus 5, 6

Other Causes

Additional causes include 5, 4, 7:

• Acute kidney injury or chronic kidney disease 4, 7
• Hyporeninemic hypoaldosteronism (particularly in diabetic nephropathy) 7
• Metabolic acidosis 2
• Tissue destruction 2
• Stored blood products (can release significant potassium during transfusion) 2

Diagnostic Considerations

The first critical step is ruling out pseudohyperkalemia from hemolysis during sample collection, excessive fist clenching, or delayed specimen processing. 2, 3, 5

Initial evaluation should include 3:

• Repeat potassium measurement with proper blood sampling technique 2, 3
• ECG immediately to assess for cardiac effects 2, 3
• Complete metabolic panel including serum electrolytes, BUN, creatinine, glucose 3
• Review of all medications for potential causative agents 3, 5
• Assessment of kidney function (eGFR) 3

Clinical Outcomes and Mortality Risk

The risk of mortality, cardiovascular morbidity, progression of CKD, and hospitalization is increased in patients with hyperkalemia, especially those with CKD, heart failure, and diabetes 1. Hyperkalemia can lead to cardiac arrest and death if untreated 5, 4

Patients with chronic kidney disease may tolerate elevated circulating potassium due to compensatory mechanisms, and several studies suggest that hyperkalemia is a less threatening condition in CKD compared to those with normal kidney function. 1