What are the causes of hyperkalemia?

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From the Guidelines

Hyperkalemia is primarily caused by renal failure, medications such as ACE inhibitors, ARBs, beta-blockers, and potassium-sparing diuretics, excessive potassium intake, cell lysis from conditions like tumor lysis syndrome or hemolysis, adrenal insufficiency, and metabolic acidosis from conditions like diabetic ketoacidosis 1.

Causes of Hyperkalemia

  • Renal failure: Decreased kidney function can lead to a buildup of potassium in the blood, as the kidneys are responsible for filtering excess potassium out of the body 1.
  • Medications: Certain medications, including ACE inhibitors (e.g., lisinopril), ARBs (e.g., losartan), beta-blockers (e.g., propranolol), and potassium-sparing diuretics (e.g., spironolactone), can increase potassium levels by reducing potassium excretion or increasing potassium retention in the body 1.
  • Excessive potassium intake: Consuming high amounts of potassium-rich foods or supplements can lead to elevated potassium levels, especially in individuals with impaired kidney function 1.
  • Cell lysis: Conditions such as tumor lysis syndrome, rhabdomyolysis, or hemolysis can release potassium from cells into the bloodstream, leading to hyperkalemia 1.
  • Adrenal insufficiency: Decreased production of aldosterone, a hormone that regulates potassium levels, can lead to hyperkalemia, as aldosterone helps promote potassium excretion in the urine 1.
  • Metabolic acidosis: Certain conditions, such as diabetic ketoacidosis, can cause a shift of potassium from cells to the bloodstream, leading to hyperkalemia 1.

To manage elevated potassium levels, it is essential to identify and address the underlying cause. In some cases, treatment may involve discontinuing or adjusting medications, reducing potassium intake, or administering medications such as potassium-binding resins (e.g., polystyrene sulfonate) or loop diuretics (e.g., furosemide) to help lower potassium levels 1. In severe cases, hospitalization and close monitoring may be necessary to prevent life-threatening complications 1.

From the FDA Drug Label

Drugs that inhibit the renin angiotensin system can cause hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes [see Drug Interactions (7.1)]. Concomitant use of other drugs that may increase serum potassium may lead to hyperkalemia [see Drug Interactions (7.1)].

The causes of hyperkalemia include:

  • Renal insufficiency
  • Diabetes mellitus
  • Concomitant use of potassium-sparing diuretics
  • Concomitant use of potassium supplements
  • Concomitant use of potassium-containing salt substitutes
  • Concomitant use of other drugs that may increase serum potassium 2 3

From the Research

Causes of Hyperkalemia

  • Hyperkalemia can result from the shift of potassium out of cells or from abnormal renal potassium excitation 4
  • Impairments in renal potassium excretion can be the result of reduced sodium delivery to the distal nephron, decreased mineralocorticoid level or activity, or abnormalities in the cortical collecting duct 4
  • Excessive intake of potassium can cause hyperkalemia but usually in the setting of impaired renal function 4
  • Drug-induced hyperkalemia is a common cause of increased potassium levels in everyday clinical practice, with a wide range of drugs causing hyperkalemia by various mechanisms, including promoting transcellular potassium shift or impairing renal potassium excretion 5
  • Common causes of hyperkalemia include kidney failure, limited delivery of sodium and water to the distal nephron, and drugs that inhibit the renin-angiotensin-aldosterone system 6
  • Hyperkalemia can also be caused by impaired renal excretion, transcellular shifts, or increased potassium intake 7

Mechanisms of Hyperkalemia

  • Drugs can interfere with potassium homeostasis either by promoting transcellular potassium shift or by impairing renal potassium excretion 5
  • The reduction in renal potassium excretion due to inhibition of the renin-elian-aldosterone system represents the most important mechanism by which drugs are known to cause hyperkalemia 5
  • Medications that alter transmembrane potassium movement include amino acids, beta-blockers, calcium channel blockers, suxamethonium, and mannitol 5
  • Drugs that impair renal potassium excretion are mainly represented by angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, calcineurin inhibitors, heparin and derivatives, aldosterone antagonists, potassium-sparing diuretics, trimethoprim, and pentamidine 5

Risk Factors

  • Patients with kidney failure or impaired renal function are at increased risk of developing hyperkalemia 4, 6
  • Patients taking medications that inhibit the renin-angiotensin-aldosterone system are also at increased risk of developing hyperkalemia 5, 6
  • Patients with limited delivery of sodium and water to the distal nephron are at increased risk of developing hyperkalemia 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Diagnosis and treatment of hyperkalemia.

Cleveland Clinic journal of medicine, 2017

Research

Drug-induced hyperkalemia.

Drug safety, 2014

Research

Management of hyperkalaemia.

The journal of the Royal College of Physicians of Edinburgh, 2013

Research

Potassium Disorders: Hypokalemia and Hyperkalemia.

American family physician, 2023

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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