• Impaired renal excretion of potassium

  • Severe reduction in glomerular filtration rate

    • Chronic kidney disease

    • Subacute-reversible

      • Volume depletion

      • Pharmacological inhibition by angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs)

  • Effective hypoaldosteronism

    • Reduced synthesis due to

      • Addison’s disease

      • Heparin administration

    • Reduced secretion of aldosterone

      • Hyporeninemia

        • Diabetic nephropathy

        • Obstructive nephropathy

        • Nonsteroidal anti-inflammatory drugs (e.g., indomethacin)

        • Cyclo-oxygenase-2 inhibitors (COX-2, e.g., Vioxx, Celebrex)

      • Reduced activity of angiotensin-converting enzyme

    • Reduced renal tubular response to aldosterone

      • Aldosterone-receptor blockers (e.g., spironolactone)

      • Type 4 renal tubular acidosis

  • Pharmacological inhibitors of distal renal tubular Na⁺-K⁺ exchange (e.g., amilioride, triamterene)

• Impaired systemic cellular accumulation of potassium

  • Hypoinsulinemia (type 1 diabetes)

  • Metabolic acidosis

  • β-andrenergic blockers (e.g., propanolol)

  • α-andrenergic agonists (e.g., phenylephrine)

• Excessive cellular release of potassium

  • Rhabdomyolosis

  • Tumor lysis

  • Leukemia

Clinical conditions that commonly occur together and that amplify their hyperkalemic effects

• Hyporeninemia/hypoaldosteronism and diabetic nephropathy

• Chronic kidney disease with either ACE or ARB therapy

SOURCE: Fisch et al. (1966); Gennari and Segal (2002); Kamel et al. (1996); Oster et al. (1995); Schoolwerth et al. (2001); Tannen (1986); Textor et al. (1982).