What are the causes of hyperkalemia (elevated potassium levels)?

From the Guidelines

Hyperkalemia, defined as a serum potassium level above 5.0 mEq/L, is primarily caused by kidney dysfunction, medication effects, and excessive potassium intake, as well as other factors such as adrenal insufficiency, acidosis, and cell breakdown conditions. The most common causes of hyperkalemia include:

• Kidney dysfunction, which impairs potassium excretion
• Medication effects, particularly from ACE inhibitors, ARBs, potassium-sparing diuretics (spironolactone, eplerenone, amiloride), NSAIDs, trimethoprim, and certain immunosuppressants like tacrolimus and cyclosporine
• Excessive potassium intake from supplements or salt substitutes Other significant causes include:
• Adrenal insufficiency (reducing aldosterone production)
• Acidosis (which drives potassium out of cells)
• Cell breakdown conditions like rhabdomyolysis, tumor lysis syndrome, and severe hemolysis
• Insulin deficiency or resistance
• Pseudohyperkalemia can occur from hemolysis during blood collection, extreme thrombocytosis, or leukocytosis
• Certain genetic disorders like Gordon syndrome and type 4 renal tubular acidosis can also cause hyperkalemia, as noted in studies such as 1 and 1. Recognizing these causes is essential for proper management, which typically involves addressing the underlying cause while implementing measures to reduce potassium levels when dangerously elevated, as discussed in 1 and 1. Patients with risk factors should have their potassium levels monitored regularly, especially when starting medications known to increase potassium levels, as recommended in 1 and 1. It is also important to consider the use of potassium-binding agents, such as patiromer sorbitex calcium and sodium zirconium cyclosilicate, which have been shown to be effective in managing hyperkalemia, as noted in 1 and 1. Overall, the management of hyperkalemia requires a comprehensive approach that takes into account the underlying causes, patient risk factors, and the use of appropriate therapies to reduce potassium levels and prevent complications, as discussed in 1.

From the Research

Causes of Hyperkalemia

The causes of hyperkalemia can be attributed to various factors, including:

• The use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) 2, 3, 4, 5
• Chronic renal insufficiency, which can lead to impaired potassium excretion 2, 3, 6, 4, 5
• Congestive heart failure, which can increase the risk of hyperkalemia in patients using ACEi or ARB 3
• Excessive potassium intake from diet, supplements, or drugs 2, 6
• Intrinsic disease of the collecting duct, disturbances in mineralocorticoid activity, and/or decreased delivery of sodium to the distal nephron 6
• The use of certain medications, such as potassium-sparing diuretics, and herbal remedies that can increase potassium levels 6

Risk Factors for Hyperkalemia

Several risk factors can increase the likelihood of developing hyperkalemia, including:

• Reduced glomerular filtration rate (GFR) 3, 6, 4, 5
• Advanced age, particularly over 70 years 3
• Diabetes mellitus, although its effect is dependent on GFR 5
• Use of long-acting ACE inhibitors 3
• High serum urea nitrogen levels 3
• Congestive heart failure 3

Clinical Considerations

When initiating ACEi or ARB therapy, it is essential to:

• Obtain an estimate of GFR and baseline serum potassium concentration 2
• Assess the patient's diet and potential sources of excessive potassium intake 2, 6
• Monitor serum potassium levels shortly after initiation of therapy to prevent hyperkalemia 2