From the Guidelines
Hyperkalemia is primarily caused by kidney dysfunction, medication effects, and excessive potassium intake, with the most significant medications being renin-angiotensin-aldosterone system inhibitors, potassium-sparing diuretics, and NSAIDs, as highlighted in the expert consensus document on the management of hyperkalaemia in patients with cardiovascular disease treated with renin angiotensin aldosterone system inhibitors 1.
Causes of Hyperkalemia
The causes of hyperkalemia can be categorized into several key areas:
- Kidney dysfunction, which impairs potassium excretion, is a major cause, especially in patients with chronic kidney disease or acute kidney injury.
- Medication effects, particularly from:
- Renin-angiotensin-aldosterone system inhibitors (RAASi) such as ACE inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists.
- Potassium-sparing diuretics like spironolactone, eplerenone, and amiloride.
- NSAIDs, which can decrease potassium excretion.
- Certain immunosuppressants like tacrolimus and cyclosporine.
- Excessive potassium intake from supplements, salt substitutes, or certain foods and herbal products.
- Other significant causes include:
- Addison's disease (adrenal insufficiency), reducing aldosterone production.
- Tissue breakdown conditions such as rhabdomyolysis, tumor lysis syndrome, and severe burns.
- Acidosis, driving potassium out of cells.
- Insulin deficiency.
- Certain hereditary conditions like Gordon syndrome.
Pseudohyperkalemia
Pseudohyperkalemia, a falsely elevated potassium reading, can occur due to:
- Hemolysis during blood collection.
- Extreme thrombocytosis or leukocytosis. It is essential to consider these factors when evaluating hyperkalemia to ensure accurate diagnosis and appropriate management, as emphasized in the European Heart Journal study 1.
Clinical Considerations
When evaluating hyperkalemia, it is crucial to:
- Review medication history.
- Assess kidney function.
- Consider recent tissue injury or metabolic derangements. Given the potential for life-threatening arrhythmias and the importance of maintaining potassium homeostasis, understanding the causes of hyperkalemia is vital for effective management, as discussed in the expert consensus document 1.
From the Research
Causes of Hyperkalemia
- Hyperkalemia can be caused by the use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) 2, 3, 4, 5, 6
- The risk of hyperkalemia is higher in patients with chronic renal insufficiency, particularly those with a glomerular filtration rate (GFR) below 15-20 mL/min 2, 3, 4
- Other risk factors for hyperkalemia include:
- Excessive potassium intake from diet, supplements, or drugs 2, 3
- Intrinsic disease of the collecting duct 3
- Disturbances in mineralocorticoid activity 3
- Decreased delivery of sodium to the distal nephron 3
- Diabetes mellitus, although this does not affect the incidence of hyperkalemia independent of GFR 4
- The use of ACEi and ARB can increase serum potassium levels, and the risk of hyperkalemia is higher in patients with reduced GFR 2, 4, 5, 6
- Hyperkalemia can also occur in patients with chronic hemodialysis, and the use of ACEi and ARB is independently associated with an increased risk of developing hyperkalemia in these patients 5
Mechanisms of Hyperkalemia
- ACEi and ARB affect potassium handling within the kidney by inhibiting the renin-angiotensin-aldosterone system, leading to decreased potassium excretion 2, 3
- The kidneys play a crucial role in maintaining potassium balance, and adaptive increases in kidney and gastrointestinal excretion of potassium help to prevent hyperkalemia in patients with chronic kidney disease (CKD) 3
- However, in patients with reduced GFR, the kidneys are less able to excrete potassium, leading to an increased risk of hyperkalemia 2, 3, 4
Clinical Implications
- Patients initiating ACEi or ARB therapy should have their serum potassium levels monitored closely, particularly those with reduced GFR or other risk factors for hyperkalemia 2, 3, 4, 5, 6
- The use of potassium-binding drugs may be useful in enabling the use of ACEi and ARB in patients with CKD, while minimizing the risk of hyperkalemia 3
- Patients with CKD should be educated on sources of potassium in the diet and should avoid the use of potassium-containing salt substitutes and herbal remedies 3