What causes hyperkalemia (high potassium levels)?

Causes of High Potassium (Hyperkalemia)

Hyperkalemia is primarily caused by impaired renal excretion, medication effects, increased potassium intake, or transcellular shifts, with chronic kidney disease and medication use being the most common etiologies in clinical practice. 1

Major Causes of Hyperkalemia

1. Impaired Renal Excretion

• Chronic Kidney Disease (CKD): Risk progressively increases as eGFR decreases, particularly when eGFR falls below 15 mL/min per 1.73 m² 1
• Acute Kidney Injury (AKI): Causes rapid reduction in potassium excretion 2
• Hyporeninemic hypoaldosteronism: Common in diabetic nephropathy 2

2. Medication-Induced Hyperkalemia

• Renin-Angiotensin-Aldosterone System Inhibitors (RAASi):
  • ACE inhibitors
  • Angiotensin II receptor blockers (ARBs)
  • Direct renin inhibitors 1
• Potassium-sparing diuretics: Spironolactone, eplerenone, amiloride, triamterene 1, 3
• Other medications:
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Calcineurin inhibitors (cyclosporine, tacrolimus)
  • Heparin and derivatives
  • Trimethoprim
  • Pentamidine
  • Beta-blockers
  • Non-selective beta-blockers (especially in overdose) 3

3. Increased Potassium Intake

• Excessive dietary potassium consumption
• Potassium-containing salt substitutes
• Potassium supplements
• Potassium-containing medications 3

4. Transcellular Shifts (Movement from Intracellular to Extracellular Space)

• Metabolic acidosis: Most common precipitating factor 4
• Insulin deficiency/hyperglycemia: Common in diabetic patients 5
• Tissue breakdown:
  • Rhabdomyolysis
  • Tumor lysis syndrome
  • Hemolysis
  • Severe burns or trauma 2
• Medications affecting cellular potassium movement:
  • Succinylcholine
  • Digoxin toxicity
  • Beta-blockers
  • Mannitol 3

High-Risk Populations

Certain patient populations have significantly increased risk for hyperkalemia 1, 6:

• Advanced CKD (especially eGFR <30 mL/min/1.73 m²)
• Heart failure
• Diabetes mellitus
• Resistant hypertension
• Recent myocardial infarction
• Advanced age
• Male sex
• Combination of these conditions

Clinical Pearls and Pitfalls

1. Medication combinations increase risk: The combination of ACE inhibitors/ARBs with potassium-sparing diuretics or NSAIDs significantly increases hyperkalemia risk 1

2. Monitoring recommendations: Patients on RAASi medications should have potassium levels monitored:

   • At initiation of therapy
   • After dose increases
   • During acute illness or dehydration 1

3. Pseudohyperkalemia: Always consider specimen hemolysis or prolonged tourniquet application as potential causes of falsely elevated potassium readings 5

4. Severity assessment: Hyperkalemia severity correlates with:

   • Absolute potassium level
   • Rate of increase
   • Presence of ECG changes
   • Underlying comorbidities 7

5. Mortality risk factors: Hyperkalemia mortality is higher with:

   • Acute kidney injury in previously normal renal function
   • Malignancy
   • Infection
   • Active bleeding
   • Multi-organ failure 4

By understanding these causes and risk factors, clinicians can better identify, prevent, and manage hyperkalemia in clinical practice.