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

From the Guidelines

Persistent hyperkalemia is most commonly caused by chronic kidney disease (CKD) and medication effects, particularly from renin-angiotensin-aldosterone system inhibitors, and requires management that addresses these underlying causes while considering potassium binders like patiromer or sodium zirconium cyclosilicate for persistent cases. The causes of persistent hyperkalemia can be multifactorial, including:

• Chronic kidney disease (CKD), which impairs potassium excretion 1, 2
• Medication effects, particularly from renin-angiotensin-aldosterone system inhibitors like ACE inhibitors (e.g., lisinopril), ARBs (e.g., losartan), and potassium-sparing diuretics (e.g., spironolactone) 1, 2, 3
• Adrenal insufficiency, which reduces aldosterone production and limits potassium secretion in the distal tubule
• Type 4 renal tubular acidosis, often seen in diabetic nephropathy, which causes hyporeninemic hypoaldosteronism and leads to potassium retention
• Excessive potassium intake from supplements, salt substitutes, or certain foods, which can overwhelm excretion mechanisms
• Tissue breakdown conditions like rhabdomyolysis, tumor lysis syndrome, or severe burns, which release intracellular potassium into circulation
• Metabolic acidosis, which drives potassium out of cells as hydrogen ions enter them
• Certain genetic disorders like Gordon syndrome (pseudohypoaldosteronism type II) and familial hyperkalemic periodic paralysis, which directly affect potassium handling Management of persistent hyperkalemia requires identifying and addressing these underlying causes, and considering potassium binders like patiromer or sodium zirconium cyclosilicate for persistent cases 2. It is also important to note that the risk of hyperkalemia increases with the severity of renal impairment, and that hyperkalemia can lead to more frequent hospitalizations and increased mortality, especially when stringent monitoring is not performed 1. In patients with heart failure, hyperkalemia can occur during ACE inhibition and may be sufficiently severe to cause cardiac conduction disturbances 3. Therefore, it is crucial to carefully monitor potassium levels and adjust treatment accordingly to prevent the complications of hyperkalemia.

From the Research

Causes of Persistent Hyperkalemia

• Impaired renal excretion of potassium, often seen in patients with chronic kidney disease (CKD) 4, 5
• Transcellular shifts of potassium, which can occur due to various factors such as insulin deficiency or resistance, and certain medications 6, 7
• Increased potassium intake, which can be due to dietary factors or certain medical conditions 5, 7
• Medications that can cause hyperkalemia, such as renin-angiotensin-aldosterone inhibitors, which can increase potassium levels by reducing potassium excretion 5

Factors Contributing to Persistent Hyperkalemia

• Underlying medical conditions, such as diabetes mellitus, heart failure, and proteinuric kidney disease, which can increase the risk of developing hyperkalemia 4, 5
• Dietary factors, such as high intake of nonplant sources of potassium, which can contribute to hyperkalemia 5
• Lack of effective diuretic therapy, which can lead to persistent hyperkalemia in patients with CKD or other conditions 5
• Inadequate management of metabolic acidosis, which can contribute to hyperkalemia in patients with CKD or other conditions 5

Consequences of Untreated Persistent Hyperkalemia

• Increased risk of cardiac dysrhythmias, which can be life-threatening 8, 6
• Muscle weakness and paralysis, which can be severe and debilitating 4, 7
• Increased morbidity and mortality, particularly in patients with underlying medical conditions 5