Hypouricemia is a medical condition marked by a low concentration of uric acid in the blood, defined as a level of 2.0 mg/dL or less. Uric acid is a natural byproduct from the body’s breakdown of purines, which are substances in food and also result from cell turnover. While excreted by the kidneys, uric acid also functions as an abundant antioxidant in the bloodstream, helping protect cells from damage. Although high uric acid levels (hyperuricemia) are more commonly discussed due to their link with gout, low levels can also signal underlying health issues.
Causes of Low Uric Acid
Diminished uric acid levels can be grouped into several categories. A significant cause is inherited genetic disorders that disrupt the body’s handling of uric acid. One such condition is renal hypouricemia, which stems from defects in proteins responsible for reabsorbing uric acid from the kidneys. When these proteins are faulty, excessive amounts of uric acid are lost in the urine. Another genetic condition is xanthinuria, where the body has difficulty producing uric acid due to a deficiency in the enzyme xanthine oxidase.
Underlying medical conditions can also lead to hypouricemia. Fanconi syndrome, a rare kidney disorder, impairs the function of kidney tubules, leading to increased uric acid excretion. Severe liver disease can diminish uric acid production, as the liver is involved in purine metabolism. Some cancers and the Syndrome of Inappropriate Antidiuretic Hormone (SIADH), which causes water retention and dilutes the blood, are other causes.
Several common medications can lower uric acid levels. Drugs that increase its excretion, known as uricosuric agents, include probenecid and high doses of aspirin. Allopurinol, a medication for gout, works by inhibiting xanthine oxidase to reduce uric acid production. Some blood pressure medications, like losartan, also have a mild urate-lowering effect.
Other contributing factors include pregnancy, significant malnutrition, or a very low-purine diet. These factors usually cause mild or transient hypouricemia. Total parenteral nutrition, a feeding method that bypasses the digestive system, has also been associated with temporarily low uric acid levels.
Associated Symptoms and Health Risks
Hypouricemia itself often produces no noticeable symptoms and is frequently discovered incidentally during routine blood tests. However, persistently low uric acid is associated with specific health risks, some of which can be serious.
A significant risk for individuals with hereditary forms like renal hypouricemia is exercise-induced acute kidney injury (EI-AKI). During strenuous physical activity, increased uric acid precursors can form crystals in the kidneys of people with this condition, causing sudden damage. Symptoms include severe flank pain, nausea, and vomiting hours after exercise.
An elevated risk of kidney stones (urolithiasis) is another health concern. While high uric acid is linked to uric acid stones, the causes of hypouricemia can lead to different stone types. For example, individuals with xanthinuria can develop xanthine stones from the buildup of xanthine in the urinary tract.
Because uric acid is an antioxidant, its deficiency may increase vulnerability to oxidative stress, though the clinical consequences are not fully understood. In rare genetic forms, neurological symptoms have been observed, but this is not a common feature.
Diagnosis and Evaluation
Diagnosis begins with a blood test measuring serum uric acid concentration. Once a low level is confirmed, the next step is to find the cause, which often involves a 24-hour urine collection to measure the total uric acid being excreted.
To differentiate between decreased production and increased excretion, clinicians calculate the fractional excretion of uric acid (FE-UA). A high FE-UA value suggests the kidneys are excreting too much uric acid, pointing toward renal hypouricemia. Conversely, a low FE-UA suggests a production issue, such as xanthinuria.
Evaluation then focuses on identifying the underlying cause. This involves reviewing the patient’s medications and ordering blood work to assess liver and kidney function. If an inherited disorder is suspected, genetic testing may be recommended to confirm a diagnosis.
Management and Treatment Approaches
The primary strategy for managing hypouricemia is to address its root cause, not to raise the uric acid level itself. If a medication is the cause, a physician may adjust it or prescribe an alternative. If it is related to an issue like SIADH or liver disease, the focus is on treating that primary disorder.
For many asymptomatic individuals with no serious underlying cause, no specific treatment is required. The finding is often considered benign, though regular monitoring may be recommended to ensure the levels remain stable.
For those with a high risk of complications, like individuals with hereditary renal hypouricemia, preventative measures are important. Patients are advised to maintain proper hydration, especially around physical exertion, and avoid strenuous exercise to prevent EI-AKI. In some medically supervised situations, allopurinol might be used before planned exercise to reduce the risk of kidney injury.