Which patients are at risk for hyperkalemia?

Patients at Risk for Hyperkalemia

Patients with advanced chronic kidney disease (CKD), heart failure (HF), resistant hypertension, diabetes, myocardial infarction (MI), and those taking renin-angiotensin-aldosterone system inhibitors (RAASi) are at highest risk for developing hyperkalemia. 1

Primary Risk Factors

Medical Conditions

• Chronic Kidney Disease (CKD)

  • Risk progressively increases as eGFR decreases 1
  • Particularly high risk when eGFR < 15 mL/min per 1.73 m² 1
  • Patients with proteinuria have increased risk 2

• Cardiovascular Conditions

  • Heart failure, especially with reduced ejection fraction (HFrEF) 1
  • Resistant hypertension 1
  • History of myocardial infarction 1

• Metabolic Disorders

  • Diabetes mellitus 1, 2
  • Metabolic acidosis 1

Medication-Related Risk Factors

• Renin-Angiotensin-Aldosterone System Inhibitors (RAASi)

  • ACE inhibitors 1
  • Angiotensin receptor blockers (ARBs) 1
  • Mineralocorticoid receptor antagonists (MRAs) like spironolactone and eplerenone 1, 2
  • Direct renin inhibitors (e.g., aliskiren) 1
  • Sacubitril/valsartan 1

• Other Medications

  • Potassium-sparing diuretics (triamterene, amiloride) 1
  • NSAIDs 1, 2
  • Beta-blockers 1
  • Heparin 1
  • Calcineurin inhibitors (cyclosporine, tacrolimus) 1
  • Trimethoprim-sulfamethoxazole 1
  • Pentamidine 1
  • Digitalis 1
  • Penicillin G 1

Combined Risk Factors

• Multiple RAASi Use

  • Dual RAAS inhibition increases hyperkalemia risk to ~5% 1
  • Triple therapy (adding MRA) increases risk to 5-10% 1

• CKD + RAASi

  • Patients with eGFR < 60 mL/min per 1.73 m² on RAASi have elevated risk 1
  • Risk increases further as eGFR decreases 1

Secondary Risk Factors

Demographic Factors

• Age

  • Advanced age increases risk 1

• Gender

  • Slightly higher risk in men than women after RAASi initiation 1

Dietary Factors

• High potassium intake from:
  • Potassium supplements 1
  • Salt substitutes 1
  • High-potassium foods (bananas, melons, orange juice) 1
  • Herbal supplements (alfalfa, dandelion, hawthorne berry) 1

Risk of Recurrent Hyperkalemia

Patients at highest risk for repeated hyperkalemia within 6 months of the first event include those with:

• Moderate to severe initial hyperkalemia (≥5.6 mEq/L) 1
• Low eGFR (<45 mL/min per 1.73 m²) 1
• Diabetes 1
• Spironolactone use 1

Clinical Implications

The risk of hyperkalemia-associated morbidity and mortality varies by patient population:

• In CKD patients, the optimal potassium range is broader (3.3-5.5 mEq/L for stage 4-5 CKD vs. 3.5-5.0 mEq/L for stage 1-2 CKD) 1
• Rapid increases in potassium are more dangerous than gradual rises 1
• Patients with CKD may develop adaptive mechanisms allowing tolerance to higher potassium levels 1

Monitoring Recommendations

• Individualize potassium monitoring frequency based on:

  • Comorbidities (especially CKD, HF, diabetes) 1
  • Medication use (particularly RAASi) 1
  • Previous episodes of hyperkalemia 1

• For patients starting RAASi therapy:

  • Measure potassium before initiating therapy 2
  • Recheck within the first week 2
  • Monitor again at one month after starting or adjusting dose 2
  • For those on moderate CYP3A inhibitors with RAASi, check potassium within 3-7 days 2

Common Pitfalls

1. Underestimating risk in patients with multiple risk factors - The combination of CKD, diabetes, and RAASi therapy substantially increases hyperkalemia risk 1

2. Inadequate monitoring - Hyperkalemia incidence may be underestimated due to lack of routine potassium monitoring even in high-risk populations 1

3. Discontinuing beneficial medications - Stopping RAASi therapy due to mild hyperkalemia may deprive patients of mortality benefits; consider potassium binders instead 1

4. Overlooking dietary sources - Failure to counsel patients about dietary potassium intake, especially in CKD 1

5. Missing drug interactions - Particularly when adding medications like trimethoprim or NSAIDs to patients already on RAASi therapy 1, 2