Causes and Risk Factors of Hyperkalemia

Hyperkalemia is the medical term for blood potassium levels that are too high. Potassium is a chemical element that is essential for life. It's especially important for the normal functioning of organ systems that rely on the transmission of electrical signals—the heart, muscles, and the nerves.

There are many factors and illnesses that can cause hyperkalemia including kidney disease, heart failure, diabetes, and certain medications. In adults, a normal potassium blood level is between 3.6 and 5.2 mEq/L. Potassium levels that are either too low (hypokalemia) or too high can become life-threatening problems.

Common Causes

There are numerous potential causes of hyperkalemia, but they can be broken down into three major categories.

Decreased Excretion of Potassium

Because the maintenance of normal potassium levels is critical to life, our kidneys have efficient mechanisms for hanging on to potassium to prevent our levels from being too low, and also for excreting excess potassium in urine to prevent our levels from being too high.

However, with either acute kidney failure or chronic kidney disease, the ability of the kidneys to excrete potassium can often become impaired, and hyperkalemia may ensue.

A decrease in the kidney's excretion of potassium may also occur with:

• Addison’s disease (failure of the adrenal glands)
• Congestive heart failure
• Cirrhosis of the liver
• Certain medications that affect the renin-aldosterone system, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, nonsteroidal anti-inflammatory drugs (NSAIDs), calcineurin inhibitors, heparin, and potassium-sparing diuretics like Aldactone and Carospir (spironolactone) and Inspra (eplerenone)

Increased Potassium Release From the Cells

Because the concentration of potassium inside of your body’s cells is roughly 30 times higher than it is in your blood, anything that causes an increased release of potassium from inside the cells to outside the cells can produce hyperkalemia.

Tissue damage can also produce a shift of potassium from the inside of cells to the outside of cells, simply by the traumatic disruption of cell membranes. Hyperkalemia from tissue damage can occur with any kind of severe trauma, burns, surgery, rapid destruction of tumor cells, hemolytic anemia, or rhabdomyolysis—the destruction of muscle cells that can occur with heat stroke or with alcoholic or drug-induced stupor.

Other potential causes of an increased release of potassium from your body's cells include:

• Insulin deficiency that results in hyperglycemia (too much glucose in your bloodstream), which can occur in poorly controlled or uncontrolled diabetes
• Insulin deficiency as a result of fasting, particularly in people who are on dialysis
• Insulin deficiency from taking somatostatin or Sandostatin (octreotide), hormones that inhibit growth hormones
• Tumor lysis syndrome, which can occur if you have lymphoma or leukemia and you're given chemotherapy or radiation therapy
• Beta-blockers
• Blood transfusions

Excessive Intake of Potassium

If you have normally functioning kidneys, it's pretty difficult to develop hyperkalemia simply from ingesting too much potassium in your diet. However, it is possible to drive blood potassium levels too high if you take large amounts of potassium supplements, especially if you also have some degree of kidney disease or if you're taking drugs that inhibit potassium excretion like the ones mentioned above.

Genetics

There are two rare hereditary disorders that can cause hyperkalemia. These can both be diagnosed with genetic testing.

Pseudohypoaldosteronism Type 1

Pseudohypoaldosteronism type 1 (PHA1) makes it hard for your body to regulate sodium, which mainly occurs in your kidneys. There are two types of PHA1:

1. Autosomal dominant PHA1, which is mild and usually improves during childhood.
2. Autosomal recessive PHA1, which is more severe and doesn't get better.

This latter disorder can lead to hyperkalemia because high amounts of sodium are released into your urine, causing low levels of sodium and high levels of potassium in your blood. In fact, hyperkalemia is considered one of the main features of this disorder.

Pseudohypoaldosteronism type 1 is caused by mutations in one of four genes that affect sodium regulation. These genes include NR3C2 (the gene that causes autosomal dominant PHA1), SCNN1A, SCNN1B, or SCNN1G, which causes autosomal recessive PHA1. This condition only affects around 1 in 80,000 newborn babies.

Pseudohypoaldosteronism Type 2

Pseudohypoaldosteronism type 2 (PHA2), also known as Gordon's syndrome, is another hereditary condition that causes hyperkalemia. This disorder makes it difficult for your body to regulate both sodium and potassium, resulting in high blood pressure and hyperkalemia, yet normal kidney function. Hyperkalemia tends to occur first, while high blood pressure develops later.

PHA2 is caused by mutations in the WNK1, WNK4, CUL3, or KLHL3 gene, all of which help regulate blood pressure. This is also a rare disorder, but it's unknown how often PHA2 occurs.

Cardiovascular

Congestive heart failure is considered one of the causes of hyperkalemia, as are some of the medications that people with heart failure often take, including diuretics, ACE inhibitors, and beta blockers. Because of this, if you have congestive heart failure and you're taking any of these life-saving medications, you may need to limit the amount of potassium you have in your diet to help reduce the risk of developing hyperkalemia. It is also likely that your healthcare provider will closely monitor the potassium levels in your blood and make sure you're on the minimum amount of the types of drugs that cause potassium levels to increase.

Lifestyle Risk Factors

If you have diabetes, among the many reasons why it's important to get your disease under control is the risk of developing hyperkalemia, which can lead to death if it becomes severe. When your diabetes is poorly controlled or uncontrolled, you end up with too much glucose in your bloodstream. This creates an insulin deficiency that can lead to hyperkalemia and other life-threatening problems. Be sure to work with your healthcare provider to find a treatment program that works for you in controlling your blood glucose so you can reduce your risks of serious and potentially life-threatening effects.