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Chapter 49.6: Hyperkalemia

David B. Mount

OVERVIEW OF HYPERKALEMIA

Hyperkalemia is defined as a plasma potassium level of 5.5 mM, occurring in up to 10% of hospitalized patients; severe hyperkalemia (>6.0 mM) occurs in ~1%, with a significantly increased risk of mortality. Although redistribution and reduced tissue uptake can acutely cause hyperkalemia, a decrease in renal K+ excretion is the most frequent underlying cause (Table 49-5). Excessive intake of K+ is a rare cause, given the adaptive capacity to increase renal secretion; however, dietary intake can have a major effect in susceptible patients, e.g., diabetics with hyporeninemic hypoaldosteronism and chronic kidney disease. Drugs that impact on the renin-angiotensin-aldosterone axis are also a major cause of hyperkalemia.

TABLE 49-5Causes of Hyperkalemia
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TABLE 49-5 Causes of Hyperkalemia

  1. Pseudohyperkalemia

    1. Cellular efflux; thrombocytosis, erythrocytosis, leukocytosis, in vitro hemolysis

    2. Hereditary defects in red cell membrane transport

  2. Intra- to extracellular shift

    1. Acidosis

    2. Hyperosmolality; radiocontrast, hypertonic dextrose, mannitol

    3. β2-Adrenergic antagonists (noncardioselective agents)

    4. Digoxin and related glycosides (yellow oleander, foxglove, bufadienolide)

    5. Hyperkalemic periodic paralysis

    6. Lysine, arginine, and ε-aminocaproic acid (structurally similar, positively charged)

    7. Succinylcholine; thermal trauma, neuromuscular injury, disuse atrophy, mucositis, or prolonged immobilization

    8. Rapid tumor lysis

  3. Inadequate excretion

    1. Inhibition of the renin-angiotensin-aldosterone axis; ↑ risk of hyperkalemia when used in combination

      1. Angiotensin-converting enzyme (ACE) inhibitors

      2. Renin inhibitors; aliskiren (in combination with ACE inhibitors or angiotensin receptor blockers [ARBs])

      3. Angiotensin receptor blockers (ARBs)

      4. Blockade of the mineralocorticoid receptor: spironolactone, eplerenone, drospirenone

      5. Blockade of the epithelial sodium channel (ENaC): amiloride, triamterene, trimethoprim, pentamidine, nafamostat

    2. Decreased distal delivery

      1. Congestive heart failure

      2. Volume depletion

    3. Hyporeninemic hypoaldosteronism

      1. Tubulointerstitial diseases: systemic lupus erythematosus (SLE), sickle cell anemia, obstructive uropathy

      2. Diabetes, diabetic nephropathy

      3. Drugs: nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase 2 (COX2) 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)

    4. 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 the epithelial sodium channel (ENaC)

    5. Advanced renal insufficiency

      1. Chronic kidney disease

      2. End-stage renal disease

      3. Acute oliguric kidney injury

    6. 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

PSEUDOHYPERKALEMIA

Hyperkalemia should be distinguished from factitious hyperkalemia or “pseudohyperkalemia,” an artifactual increase in serum K+ due to the release of K+ during or after venipuncture. Pseudohyperkalemia can occur in the setting of excessive muscle activity during venipuncture (e.g., fist clenching), a marked increase in cellular elements (thrombocytosis, leukocytosis, and/or erythrocytosis) with in vitro efflux of K+, and acute anxiety during venipuncture with respiratory alkalosis and redistributive hyperkalemia. Cooling of blood following venipuncture is another ...

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