Hypouricemia

Causes of Decrease in Uric Acid Levels

Why Do Uric Acid Levels Decrease?

If a hematology test presents uric acid levels to be lower than 2 mg/dL, it is diagnosed as hypouricemia. Why do uric acid levels decrease? Uric acid levels decrease not only due to the effects of some drugs but also due to other unrelated factors.

A Case that Uric Acid Generated in the Body is Excreted Too Rapidly

Approximately 70% of uric acid which is generated in the body is excreted from the kidneys into the urine. In the kidneys, a larger amount of uric acid is initially excreted into the urine and the majority of the uric acid is reabsorbed through the renal tubules. However, in some cases, there are mutations in the genes which are responsible for the function of reabsorption. Due to these mutations, uric acid generated in the body is not reabsorbed sufficiently and a large amount is excreted to outside the body, lowering the uric acid levels. This condition is called renal hypouricemia.

Among Japanese people who were diagnosed with hypouricemia, most people present renal hypouricemia. While symptoms other than the decrease in the uric acid levels due to the inability to reabsorb uric acid have not been confirmed, low uric acid levels tend to cause some complications. Major complications include exercise-induced acute renal failure and urolithiasis. Exercise-induced acute renal failure is likely to develop with a combination of anaerobic exercise (i.e. intense exercise) and dehydration or administration of NSAID. People having renal hypouricemia should be attentive to intensive exercises and dehydration to prevent complications. Staying hydrated will also lead to preventing urolithiasis.

A Case that Uric Acid is Not Generated in the Body

Cells are degraded in our body after their roles are completed. Purines which constitute nucleic acids (DNA) of cells are degraded into hypoxanthine and then into xanthine to finally become uric acid. However, if there is a deficiency of xanthine oxidoreductase (XOR) that facilitates the degradation of purines into uric acid, purines are unable to be degraded into uric acid and cause a decrease of blood uric acid levels.

A disease in which uric acid cannot be generated due to XOR deficiency is called xanthinuria and it is very rare. While symptoms other than lower uric acid levels have not been confirmed, it is confirmed that people with xanthinuria are more likely to develop a complication of urolithiasis. It is recommended to stay hydrated on a regular basis to prevent urolithiasis and to consciously follow a diet that is low in purines.

A Case that Uric Acid Levels are Decreased As Secondary Effects of Drug Administration or Other Factors

Furthermore, there are some cases that administration of drugs which have effects on renal failure, malignant tumor, diabetes or uric acid cause a decrease in uric acid levels.

Hypouricemia with Hyperactive Extrarenal Excretion of Uric Acid (Uric acid is excreted excessively)

• Fanconi syndrome
• Wilson’s disease
• Syndrome of inappropriate antidiuretic hormone secretion
• Malignant Tumor
• Diabetes
• Drug (e.g. Benzbromarone, Probenecid)
• Pregnancy
• Intractable Diarrhea

Hypouricemia with Reduced Uricopoiesis (Uric acid is not generated in the body)

• Molybdenum Cofactor Deficiency
• Purine Nucleoside Phosphorylase Deficiency
• PRPP Synthetase Hypoactivity
• Idiopathic Hypouricemia with Lowering of Uricopoiesis
• Severe Renal Failure
• Drugs (e.g.: Allopurinol)
• Emaciation (Undernutrition)

Unlike renal hypouricemia or xanthinuria, the above diseases often require treatments. Therefore, please follow the doctor’s diagnosis and instructions.