What are the causes of hyperkalemia (elevated potassium levels)?

From the Guidelines

Hyperkalemia is primarily caused by kidney dysfunction, medication effects, and excessive potassium intake, and its management should prioritize addressing the underlying cause while implementing measures to lower potassium levels. The most common causes of hyperkalemia include kidney dysfunction, which impairs potassium excretion; medication effects, particularly from ACE inhibitors, ARBs, potassium-sparing diuretics (spironolactone, eplerenone, amiloride), NSAIDs, trimethoprim, and certain immunosuppressants like tacrolimus; and excessive potassium intake from supplements or salt substitutes 1. Other significant causes include adrenal insufficiency (which reduces aldosterone production), tissue breakdown conditions like rhabdomyolysis or tumor lysis syndrome (which release intracellular potassium), metabolic acidosis (which drives potassium out of cells), insulin deficiency, and certain hereditary conditions like Gordon syndrome.

Key Causes of Hyperkalemia

• Kidney dysfunction
• Medication effects (e.g., ACE inhibitors, ARBs, potassium-sparing diuretics)
• Excessive potassium intake from supplements or salt substitutes
• Adrenal insufficiency
• Tissue breakdown conditions (e.g., rhabdomyolysis, tumor lysis syndrome)
• Metabolic acidosis
• Insulin deficiency
• Hereditary conditions (e.g., Gordon syndrome)

Pseudohyperkalemia, a falsely elevated potassium reading, can occur with hemolysis during blood collection, extreme thrombocytosis, or leukocytosis 1. Hyperkalemia is particularly dangerous because it can cause cardiac arrhythmias and requires prompt identification of the underlying cause for effective management. According to the most recent and highest quality study, treatment typically involves addressing the cause while simultaneously implementing measures to lower potassium levels, such as calcium administration for cardiac protection, insulin with glucose, beta-agonists, or dialysis in severe cases 1.

Management of Hyperkalemia

• Addressing the underlying cause
• Implementing measures to lower potassium levels (e.g., calcium administration, insulin with glucose, beta-agonists, dialysis)
• Monitoring and adjusting treatment as needed to prevent complications and improve patient outcomes.

From the Research

Causes of Hyperkalemia

• Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L 2
• Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice 2
• A wide range of drugs can cause hyperkalemia by a variety of mechanisms, including:
  • Promoting transcellular potassium shift
  • Impairing renal potassium excretion
  • Increasing potassium supply
• Medications that can induce hyperkalemia include:
  • Angiotensin-converting enzyme inhibitors
  • Angiotensin-II receptor blockers
  • Direct renin inhibitors
  • Nonsteroidal anti-inflammatory drugs
  • Calcineurin inhibitors
  • Heparin and derivatives
  • Aldosterone antagonists
  • Potassium-sparing diuretics
  • Trimethoprim
  • Pentamidine
  • Potassium-containing agents 2, 3, 4, 5
• Underlying conditions that can increase the risk of hyperkalemia include:
  • Chronic kidney disease (CKD)
  • Acute kidney injury (AKI)
  • Heart failure
  • Diabetes mellitus 3, 4, 6
• Other factors that can contribute to hyperkalemia include:
  • Reduced renal potassium excretion due to inhibition of the renin-angiotensin-aldosterone system 2
  • Increased potassium intake
  • Cellular breakdown or tissue damage 6