Why does impaired renal (kidney) function cause hyperkalemia (elevated potassium levels)?

From the Guidelines

Kidney failure causes potassium levels to rise because the kidneys are primarily responsible for removing excess potassium from the body, and when they fail, they lose their ability to filter potassium properly, leading to its accumulation in the bloodstream, a condition called hyperkalemia. When kidneys fail, they are unable to effectively excrete potassium, leading to its buildup in the blood 1. Normally, healthy kidneys filter blood and excrete excess potassium through urine, maintaining blood potassium within a narrow range of 3.5-5.0 mEq/L. In kidney failure, this regulatory mechanism breaks down, and potassium levels can rise to dangerous levels.

Some key factors that contribute to hyperkalemia in kidney failure include:

• Decreased potassium excretion due to impaired kidney function
• Metabolic acidosis, which often accompanies kidney failure, causing potassium to move from inside cells into the bloodstream, further elevating levels
• Certain medications used to treat kidney disease, such as renin-angiotensin-aldosterone system inhibitors (RAASi), which can increase potassium levels 1
• Increased potassium intake or administration from various sources, including dietary supplements, certain foods, and medications 1

Elevated potassium is dangerous because it can disrupt normal heart rhythm, potentially causing life-threatening arrhythmias. Treatment of hyperkalemia often requires a combination of immediate interventions, such as calcium carbonate and hyperosmolar sodium, as well as longer-term management with potassium-lowering agents, like loop diuretics and potassium binders 1. Patients with kidney failure often need to limit dietary potassium intake, avoid potassium supplements, and may require medications like sodium polystyrene sulfonate (Kayexalate) or patiromer (Veltassa) to help remove excess potassium from the body.

From the Research

Kidney Failure and Potassium Levels

• Kidney failure can cause potassium levels to rise due to decreased renal potassium (K+) secretion, as seen in patients with acute or chronic renal failure (ARF or CRF) 2.
• The decrease in K+ secretion by the distal tubule may be due to a decrease in tubular fluid flow rate or diminished circulating aldosterone concentrations 2.
• Patients with chronic kidney disease (CKD) are at risk of hyperkalemia due to reduced urinary potassium excretion, which is associated with a decline in glomerular filtration rate 3.

Factors Contributing to Hyperkalemia

• High potassium intake, advanced age, diabetes mellitus, congestive heart failure, and medications such as renin-angiotensin-aldosterone system (RAAS) blockades can increase the risk of hyperkalemia in CKD patients 3, 4.
• The use of RAAS blockades, which are first-line treatments for cardio- and nephroprotection, can also contribute to hyperkalemia, resulting in high rates of discontinuation 5.

Consequences of Hyperkalemia

• Hyperkalemia can increase the risk of cardiac arrhythmia episodes and sudden death, making it essential to control potassium elevation in CKD patients 4.
• Both hyperkalemia and hypokalemia are independently associated with higher rates of death, major adverse cardiovascular events, hospitalization, and discontinuation of RAAS blockers in patients with CKD 6.

Management of Hyperkalemia

• The management of hyperkalemia includes orientation of low potassium diets, monitoring of patients' adherence, and the use of potassium binders such as sodium polystyrene sulfonate (SPS), calcium polystyrene sulfonate (CPS), patiromer, and sodium zirconium cyclosilicate (ZS-9) 3, 4, 5.
• Newer therapeutic agents, such as sodium/glucose-cotransporter-2 inhibitors and mineralocorticoid-receptor-antagonists, have shown promising results in the treatment of hyperkalemia 5.