Causes of Hyperkalemia
Hyperkalemia is primarily caused by decreased potassium excretion, increased potassium intake, or transcellular potassium shifts, with medication use and renal impairment being the most common clinical factors. 1, 2
Common Causes of Hyperkalemia
1. Decreased Potassium Excretion
Renal dysfunction:
Medications that decrease potassium excretion 1:
- Renin-angiotensin-aldosterone system inhibitors (RAASi):
- ACE inhibitors
- Angiotensin receptor blockers (ARBs)
- Direct renin inhibitors (aliskiren)
- Mineralocorticoid receptor antagonists (MRAs)
- Potassium-sparing diuretics (spironolactone, triamterene, amiloride)
- NSAIDs
- Beta-blockers
- Calcineurin inhibitors (cyclosporine, tacrolimus)
- Trimethoprim-sulfamethoxazole
- Heparin
- Pentamidine
- Digitalis
- Sacubitril/valsartan
- Mannitol
- Penicillin G
- Renin-angiotensin-aldosterone system inhibitors (RAASi):
2. Increased Potassium Intake or Administration
- Excessive dietary potassium intake 1:
- Potassium supplements
- Salt substitutes
- High-potassium foods (bananas, melons, orange juice)
- Herbal supplements (alfalfa, dandelion, hawthorne berry, nettle, noni juice)
- Stored blood products transfusion 1
- Intravenous potassium administration
3. Transcellular Shifts (Movement from Intracellular to Extracellular Space)
- Metabolic acidosis
- Insulin deficiency/hyperglycemia
- Cell lysis (tumor lysis syndrome, rhabdomyolysis, hemolysis)
- Medications affecting cellular potassium transport
- Hyperkalemic periodic paralysis
4. Pseudo-hyperkalemia
- Hemolysis during blood collection
- Thrombocytosis
- Leukocytosis
- Prolonged tourniquet use
- Fist clenching during blood draw 1
High-Risk Populations
Hyperkalemia risk is significantly higher in patients with:
- Advanced CKD (present in up to 73% of patients) 1
- Heart failure (present in up to 40% of patients) 1
- Diabetes mellitus 1
- Advanced age 1
- Combination of these conditions 1
- Male gender (slightly higher risk than females) 1
Clinical Significance
Hyperkalemia can be classified as:
- Mild (5.0-5.5 mmol/L)
- Moderate (5.6-6.5 mmol/L)
- Severe (>6.5 mmol/L) 2
Even mild hyperkalemia (>5.0 mmol/L) is associated with increased mortality risk, particularly in patients with heart failure, CKD, or diabetes 2. Severe hyperkalemia can lead to cardiac arrhythmias, cardiac arrest, and death 1.
Prevention Strategies
For patients at risk of hyperkalemia:
- Monitor serum potassium regularly, especially in high-risk patients
- Review and adjust medications that can cause hyperkalemia
- Consider dietary potassium restriction in advanced CKD
- Implement lifestyle modifications including sodium restriction (<2g/day) and regular physical activity 2
- Avoid potassium-containing IV fluids in at-risk patients 2
- Consider potassium binders for chronic management in high-risk patients 2
Important Clinical Considerations
- Hyperkalemia is often asymptomatic and discovered incidentally on routine blood tests 1
- The worldwide incidence may be underestimated due to lack of routine potassium monitoring 1
- Chronic or recurrent hyperkalemia is defined as potassium levels >5 mEq/L repetitively measured over a 1-year period 1
- Always rule out pseudo-hyperkalemia when an unexpectedly high potassium level is found 1
Understanding these causes and risk factors is essential for early identification, prevention, and management of hyperkalemia in clinical practice.