Causes of Hyperkalemia
Hyperkalemia is most commonly caused by medications that interfere with potassium homeostasis, particularly those that inhibit the renin-angiotensin-aldosterone system, along with renal impairment that reduces potassium excretion. 1, 2
Major Causes of Hyperkalemia
1. Medication-Related Causes
Medications represent the most important cause of hyperkalemia in clinical practice 2:
Medications that inhibit the renin-angiotensin-aldosterone system:
- ACE inhibitors
- Angiotensin II receptor blockers (ARBs)
- Direct renin inhibitors
- Aldosterone antagonists (spironolactone, eplerenone)
- Potassium-sparing diuretics (amiloride, triamterene)
Medications that impair renal potassium excretion:
- NSAIDs
- Calcineurin inhibitors (cyclosporine, tacrolimus)
- Heparin and derivatives
- Trimethoprim
- Pentamidine
Medications that cause transcellular potassium shift:
- Beta-blockers (especially non-selective)
- Calcium channel blockers
- Succinylcholine
- Mannitol
- Amino acids
Potassium-containing medications and supplements:
- Potassium supplements
- Salt substitutes
- Certain herbal preparations
2. Renal Causes
- Acute kidney injury
- Chronic kidney disease (especially eGFR <60 mL/min/1.73m²)
- Hyporeninemic hypoaldosteronism (common in diabetic nephropathy)
- Tubular disorders affecting potassium secretion
3. Endocrine Disorders
- Adrenal insufficiency (Addison's disease)
- Hypoaldosteronism
- Diabetes mellitus (particularly with advanced age >65 years)
4. Excessive Potassium Intake
- High potassium diet in susceptible individuals
- Rapid intravenous potassium administration
- Blood transfusions (especially stored blood)
5. Cellular Shifts
- Acidosis (metabolic or respiratory)
- Tissue breakdown:
- Rhabdomyolysis
- Tumor lysis syndrome
- Severe burns or trauma
- Hemolysis
Risk Factors for Hyperkalemia
- Advanced age (>65 years)
- Diabetes mellitus
- Chronic kidney disease
- Heart failure
- Concurrent use of multiple potassium-altering medications
- Dehydration
High-Risk Medication Combinations
- Triple therapy with beta blockers + ACEIs/ARBs + MRAs carries particularly high risk 1
- Combination of potassium-sparing diuretics with ACE inhibitors 1
- NSAIDs with ACE inhibitors or ARBs
- Multiple potassium-sparing medications used concurrently
Clinical Pearls and Pitfalls
- Hyperkalemia in patients with mild-to-moderate renal failure should not be attributed to renal failure alone - always search for additional causes, especially medications 3
- Multiple causes of hyperkalemia often coexist in the same patient - conduct a systematic evaluation 3
- Patients with diabetes are at increased risk of beta blocker-induced hyperkalemia, particularly those over 65 years 1
- Regular potassium monitoring is essential when starting or adjusting medications that affect potassium levels - check within 2-3 days after medication changes 1
- ECG changes may not correlate well with serum potassium levels, so clinical assessment is crucial 4
Hyperkalemia is a potentially life-threatening condition that requires prompt recognition and management, with particular attention to medication review and renal function assessment in all cases.