Hypouricemia

Hypouricemia or hypouricaemia is a level of uric acid in blood serum that is below normal. In humans, the normal range of this blood component has a lower threshold set variously in the range of 2 mg/dL to 4 mg/dL, while the upper threshold is 530 μmol/L (6 mg/dL) for women and 619 μmol/L (7 mg/dL) for men. Hypouricemia usually is benign and sometimes is a sign of a medical condition.

Complications
Although normally benign, idiopathic renal hypouricemia may increase the risk of exercise-induced acute kidney failure. There is also evidence that hypouricemia can worsen conditions such as rheumatoid arthritis, especially when combined with low Vitamin C uptake, due to free radical damage.

Causes
Hypouricemia is often benign and not a medical condition, but it is a useful medical sign. It is known occasionally to result in a decreased ability to concentrate urine due to decreased hypertonicity of the renal medulla, and may contribute to hypotension when other risk factors are present. Hypotonicity of the renal medulla is considered normal in the fetus and in infants due to hypouricemia caused by low protein intake. Hypouricemia is usually due to drugs and toxic agents, sometimes to diet or genetics, and, rarely, suggests an underlying medical condition.

Medication
The majority of drugs that contribute to hypouricemia are uricosuric drugs that increase the excretion of uric acid from the blood into the urine. Others include drugs that reduce the production of uric acid: xanthine oxidase inhibitors, urate oxidase (rasburicase), and sevelamer.

Diet
Hypouricemia is common in vegetarians and vegans due to the low purine content of most vegetarian diets. Vegetarian diet has been found to result in mean serum uric acid values as low as 239 μmol/L (2.7 mg/dL). While a vegetarian diet is typically seen as beneficial with respect to conditions such as gout, it may be associated with some other health conditions.

Transient hypouricemia sometimes is produced by total parenteral nutrition. Paradoxically, total parenteral nutrition may produce hypouricemia followed shortly by acute gout, a condition normally associated with hyperuricemia. The reasons for this are unclear.

Genetics
Two kinds of genetic mutations are known to cause hypouricemia: mutations causing xanthine oxidase deficiency, which reduces the production of uric acid;  and mutations causing abnormal kidney function that increases the excretion of uric acid. Collectively known as familial renal hypouricemia, the latter mutations are of two types, involving defects of presecretory and postsecretory reabsorption.

A genetic mutation in Dalmatian dogs causes hypouricemia due to a kidney defect that interferes with reabsorption of uric acid. A similar mutation has been reported in a human brother and sister.

In humans, loss-of-function mutations in the gene URAT1 are associated with presecretory reabsorption defects.

Medical conditions
Medical conditions that can cause hypouricemia include:
 * Fanconi syndrome
 * Hyperthyroidism
 * Multiple sclerosis
 * Myeloma
 * Nephritis
 * Wilson's disease
 * Purine nucleoside phosphorylase (PNP) deficiency

Diagnosis
Uric acid clearance should also be performed, increase in clearance points to proximal tubular defects in the kidney, normal or reduced clearance points to a defect in xanthine oxidase.

Treatment
Idiopathic hypouricemia usually requires no treatment. In some cases, hypouricemia is a medical sign of an underlying condition that does require treatment. For example, if hypouricemia reflects high excretion of uric acid into the urine (hyperuricosuria) with its risk of uric acid nephrolithiasis, the hyperuricosuria may require treatment.

Drugs and dietary supplements that may be helpful

 * Inositol
 * Antiuricosurics

Prevalence
In one study, hypouricemia was found in 4.8% of hospitalized women and 6.5% of hospitalized men. (The definition was less than 0.14 mmol/L for women and less than 0.20 mmol/L in men.)