What diseases are associated with hyperkalemia?

Diseases and Conditions Associated with Hyperkalemia

Hyperkalemia is primarily associated with chronic kidney disease, heart failure, diabetes mellitus, and medication use—particularly renin-angiotensin-aldosterone system (RAAS) inhibitors—with chronic kidney disease being the most important predisposing condition due to impaired potassium excretion. 1, 2, 3

Primary Disease States

Chronic Kidney Disease (CKD)

• Patients with CKD represent the most severely affected group for hyperkalemia development, with up to 73% of those with advanced CKD at risk 1
• The incidence increases dramatically with severity of renal impairment, particularly when eGFR falls below 15 mL/min/1.73 m² 1
• CKD patients have decreased ability to excrete potassium and commonly have additional predisposing conditions that cluster together 3
• These patients require potassium binders for both acute episodes and chronic hyperkalemia management 4

Heart Failure

• Up to 40% of patients with chronic heart failure are at risk of developing hyperkalemia 1
• In heart failure with reduced ejection fraction (HFrEF), up to one-third of patients starting mineralocorticoid receptor antagonists (MRAs) develop hyperkalemia (>5.0 mEq/L) over 2 years 5, 1
• In real-world settings, the incidence can reach 50% in unselected populations receiving RAAS inhibitors, far exceeding the 6-12% seen in controlled clinical trials 1

Diabetes Mellitus

• Diabetic patients are at increased risk of developing both initial and recurrent hyperkalemia 1, 2
• Hyperglycemia itself can cause transcellular potassium shifts leading to hyperkalemia 6
• Diabetes commonly coexists with CKD, compounding the risk 3

Medication-Induced Hyperkalemia

RAAS Inhibitors

• ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists (spironolactone, eplerenone) are the most important medication-related causes 5, 1
• Patients with cardiovascular disease and CKD on RAAS inhibitors have 50% experiencing two or more recurrences within 1 year 1
• Hyperkalaemia was the reason for non-use of ACE inhibitors/ARBs in 8.5% and MRAs in 35.1% of heart failure patients 5

Other High-Risk Medications

• Potassium-sparing diuretics (amiloride, triamterene) impair renal potassium excretion 1
• NSAIDs impair renal potassium excretion through prostaglandin inhibition 1, 2
• Aliskiren (direct renin inhibitor) increases hyperkalemia risk 1
• Calcium channel blockers can cause hyperkalemia 1
• Succinylcholine and digitalis are associated with hyperkalemia 2

Additional Clinical Conditions

Acute Tissue Injury

• Significant tissue trauma releases intracellular potassium into the bloodstream 2
• Tumor lysis syndrome from rapid tumor cell destruction can release massive amounts of intracellular potassium within 12-72 hours after initiating chemotherapy, radiation, or cytolytic antibody therapy 1
• This occurs most commonly in malignancies with high proliferative rates and can cause life-threatening cardiac arrhythmias 1

Metabolic Acidosis

• Metabolic acidosis causes transcellular shifts of potassium from intracellular to extracellular space 5, 7

High-Risk Patient Populations

Elderly Patients

• Elderly patients are at increased risk independent of other factors 1

Patients with Multiple Risk Factors

• Initial moderate to severe hyperkalemia (>5.6 mEq/L) predicts recurrent episodes 1
• Low eGFR (<45 mL/min/1.73 m²) significantly increases recurrence risk 1
• Patients on spironolactone with diabetes and reduced kidney function represent the highest-risk group 1

Critical Clinical Pitfall

The most important pitfall is discontinuing RAAS inhibitors after a single elevated potassium measurement, as this offsets the survival benefits of these medications—less than one-third of patients achieve guideline-recommended target doses due to premature discontinuation 1. Instead, initiate potassium-lowering agents while maintaining RAAS inhibitor therapy unless severe hyperkalemia (>6.5 mEq/L) develops 7.