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Table 1-4

Causes of Hyperkalemia

  • “Pseudo” hyperkalemia
    • Cellular efflux: thrombocytosis, erythrocytosis, leukocytosis, in vitro hemolysis
    • Hereditary defects in red cell membrane transport
  • Intra- to extracellular shift
    • Acidosis
    • Hyperosmolality; radiocontrast, hypertonic dextrose, mannitol
    • β-Adrenergic antagonists (noncardioselective agents)
    • Digoxin and related glycosides (yellow oleander, foxglove, bufadienolide)
    • Hyperkalemic periodic paralysis
    • Lysine, arginine, and ε-aminocaproic acid (structurally similar, positively charged)
    • Succinylcholine; thermal trauma, neuromuscular injury, disuse atrophy, mucositis, or prolonged immobilization
    • Rapid tumor lysis
  • Inadequate excretion
    • Inhibition of the renin-angiotensin-aldosterone axis; ↑ risk of hyperkalemia when used in combination or at higher than recommended dosages
      1. ACE inhibitors
      2. Renin inhibitors: aliskiren (in combination with ACE inhibitors or ARBs)
      3. ARBs
      4. Blockade of the mineralocorticoid receptor: spironolactone, eplerenone, drospirenone
      5. Blockade of ENaC: amiloride, triamterene, trimethoprim, pentamidine, nafamostat
    • Decreased distal delivery
      1. Congestive heart failure
      2. Volume depletion
    • Hyporeninemic hypoaldosteronism
      1. Tubulointerstitial diseases: SLE, sickle cell anemia, obstructive uropathy
      2. Diabetes, diabetic nephropathy
      3. Drugs: nonsteroidal anti-inflammatory drugs, COX-2 inhibitors, β blockers, cyclosporine, tacrolimus
      4. Chronic kidney disease, advanced age
      5. Pseudohypoaldosteronism type II: defects in WNK1 or WNK4 kinases, Kelch-like 3 (KLHL3), or Cullin 3 (CUL3)
    • Renal resistance to mineralocorticoid
      1. Tubulointerstitial diseases: SLE, amyloidosis, sickle cell anemia, obstructive uropathy, post-acute tubular necrosis
      2. Hereditary: pseudohypoaldosteronism type I: defects in the mineralocorticoid receptor or ENaCE. Advanced renal insufficiency with low GFR
    • Advanced renal insufficiency with low GFR
      1. Chronic kidney disease
      2. End-stage renal disease
      3. Acute oliguric kidney injury
    • Primary adrenal insufficiency
      1. Autoimmune: Addison's disease, polyglandular endocrinopathy
      2. Infectious: HIV, cytomegalovirus, tuberculosis, disseminated fungal infection
      3. Infiltrative: amyloidosis, malignancy, metastatic cancer
      4. Drug-associated: heparin, low-molecular-weight heparin
      5. Hereditary: adrenal hypoplasia congenita, congenital lipoid adrenal hyperplasia, aldosterone synthase deficiency
      6. Adrenal hemorrhage or infarction, including in antiphospholipid syndrome

Abbreviations: ARB, angiotensin receptor blocker; COX-2, cyclooxygenase 2; ENaC, epithelial Na+ channels.