Hyperuricosuria and Gouty Diathesis

Updated: Jan 26, 2022
  • Author: Bijan Shekarriz, MD; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
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Practice Essentials

Hyperuricosuria is defined as urinary excretion of uric acid greater than 800 mg/day in men and greater than 750 mg/day in women. Uric acid, the major end-product of purine metabolism, is relatively insoluble in water. This excess uric acid leads to the formation of uric acid calculi. Such high levels may be due to either excess dietary intake of purine-rich foods or endogenous uric acid overproduction. Hyperuricosuria may be associated with hyperuricemia. In contrast, the term gouty diathesis describes the formation of urinary stones in persons with primary gout. These patients may present with other manifestations of gout (eg, gouty arthritis).

Uric acid–related nephrolithiasis may involve pure calcium stones, uric acid stones, or a combination of both. Furthermore, uric acid stones may develop in persons with normal urinary and serum levels of uric acid. Unlike most other forms of urolithiasis, medical therapy is an integral part of management of uric acid stones. Therefore, an understanding of the pathophysiology of uric acid–related nephrolithiasis is important for a cost-effective treatment approach.

In patients with hyperuricosuria, dietary purine restriction is the initial treatment. If that proves insufficient, pharmacologic intervention with allopurinol may be considered, especially in patients with primary gout. [1]  



The urinary solubility of uric acid depends on its concentration in urine and the urinary pH. At a pH below 5.5, nearly 100% of uric acid exists in an undissociated form. The 3 mechanisms responsible for uric acid related stone formation include (1) an acidic urinary milieu, (2) dehydration, and (3) hyperuricosuria. One or more of these factors may be found in patients with uric acid–related calculi. However, persistently acidic urine (ie, pH < 5.5) is the most important factor observed in patients with uric acid stones. Patients with gouty diathesis have consistently acidic urine (pH < 5.5) and elevated levels of serum uric acid. Urine uric acid levels in these patients may be elevated or within the reference range.

Although the mechanism of low urinary pH in many patients may not be completely clear and can be multifactorial, studies suggest an association between diabetes and insulin resistance in patients with normal urinary uric acid levels and acidic urine. [2] Therefore, a subset of patients with idiopathic uric acid stones may have a broader systemic disorder of insulin resistance. A manifestation of insulin resistance is a mild defect in ammonium excretion that can result in stone formation. Acidic urine and uric acid stones have been reported as more common in patients with non–insulin-dependent diabetes than in patients with stones who do not have diabetes. The loss of diurnal variation in urinary pH and dietary content are other factors that contribute to acidity of the urine.

Hyperuricosuria is defined as urinary uric acid levels that exceed 800 mg/day in men and 750 mg/day in women. The most common cause of hyperuricosuria is increased dietary purine intake, but many other hereditary or acquired factors (eg, gout) may result in this condition. Individuals with hyperuricosuria may develop uric acid or calcium oxalate stones due to supersaturation of urine with monosodium urate. Monosodium urate may initiate calcium oxalate stone formation by the induction of heterogeneous nucleation or by absorption of certain inhibitors. Patients with calcium oxalate stones have a urinary pH of greater than 5.5.

Finally, all conditions that contribute to low urinary volume may increase uric acid supersaturation in urine and result in uric acid stone formation.



Hyperuricosuric calcium nephrolithiasis is characterized by calcium oxalate or calcium phosphate stones in persons with hyperuricosuria. The hyperuricosuria is most commonly due to an excessively purine-rich diet; however, hyperuricosuria may be related to overproduction of uric acid in as many as 30% of these patients. This may represent a latent form of gout. In contrast to calcium-based stones, uric acid stones form in an acidic environment with a urinary pH that is always below 5.5.

The solubility of uric acid depends on three factors: urinary pH, uric acid concentration, and urinary volume. The causes of uric acid stones can be categorized according to those three factors.

Acidic urine may result from any of the following:

  • Gouty diathesis
  • Chronic diarrhea
  • Inflammatory bowel disease
  • Exercise/dehydration
  • Familial
  • Obesity, diabetes, and the metabolic syndrome - Strong association with low urinary pH [3]

Hyperuricosuria may result from any of the following:

  • Gouty diathesis
  • An excessively purine-rich diet
  • Inborn errors of metabolism (ie, hypoxanthine-guanine phosphoribosyl-transferase deficiency, phosphoribosylpyrophosphate synthetase overactivity, glucose-6-phosphatase synthetase deficiency
  • Myeloproliferative disorders (eg, leukemia, hemolytic anemia, neoplasia)
  • Medications
  • Chemotherapy

Low urinary volume may result from any of the following:

  • GI disorders
  • Strenuous exercise/dehydration


In the United States, uric acid stones account for 5-10% of urinary stones. Approximately 15-20% of patients with calcium stones have hyperuricosuria. Up to 20% of patients with gout develop uric acid stones. [4]

The frequency of uric acid–related stones in other Western countries is similar to that in the United States; however, the proportion of uric acid stones varies between countries and accounts for 5% to 40% of all urinary calculi. For example, an analysis of stones in gout patients in Japan showed that the incidence of uric acid stones was 30%. [4]

In a retrospective study of 260 returning patients at a tertiary center in Israel, the prevalence of hyperuricosuria was 16.5%. Other metabolic abnormalities detected were hypocitraturia (60%), low urine volume (LUV) (60%), hypercalciuria (40.8%), hyperoxaluria (24.2%), and hyperuricemia (13.5%). Stone compositions was calcium-oxalate (81%), calcium-phosphate (11.9%) and uric acid (7.1%). [5]

In a cross-sectional study of 2,861 patients with kidney stones in the United Kingdom (2,016 male), the prevalence of hyperuricosuria was 18%. The prevalence of other risk factors included low urine volume, 5.6%; hypercalciuria, 38%; hyperoxaluria, 7.9%; and hypocitraturia, 38%. Most stones were mixed in composition, with around 90% containing some proportion of calcium salts. [6]

Approximately 80-90% of persons with hyperuricosuric calcium nephrolithiasis are men. Similarly, most individuals (70%) with calcium stones who do not have hyperuricosuria are also men. Uric acid stones are more common in men than in women. Most uric acid stones are not associated with gout. Dehydration and urine acidity predispose patients to uric acid stones. Gout is mainly a disorder of men; only 5% of cases occur in women.

Hyperuricosuric calcium nephrolithiasis and gouty diathesis usually manifest in middle-aged individuals. In men, the peak age of onset of clinical gout is approximately 45 years.



The prognoses of the familial and genetic forms depend on the primary disease and associated abnormalities. With appropriate diagnosis and treatment, most patients survive with minimal long-term morbidity. In the chronic phase, recurrent obstruction and infections rarely lead to loss of renal function.

Untreated urinary stones may result in urinary obstruction (with or without pain) and subsequent urinary tract infection. If severe, this may result in life-threatening urosepsis. This condition requires immediate resolution of obstruction.

Severe hyperuricemia may result in acute urate nephropathy in patients with myeloproliferative or lymphoproliferative disorders. The mechanism of urate nephropathy involves precipitation of urate within the renal tubules, with subsequent intratubular obstruction and severe azotemia.


Patient Education

With appropriate diet and medical therapy, uric acid–related urolithiasis is a preventable disease. Patients should be instructed to maintain a daily fluid intake sufficient to generate a urinary output of at least 1.5-2 L, to avoid an excessively purine-rich diet (eg, red meat, solid-organ meats), and to limit the sodium content of their diet.

Patients with uric acid stones should be instructed to measure their urinary pH at home with the aid of nitrazine pH paper and to adjust their dosage of the alkalinizing agent accordingly. Generally, achieving and maintaining a urinary pH in the range of 6.5-7.0 requires a motivated and compliant patient. 

UriDynamics, Inc offers an improved urinary dipstick (Stone Guard 2) specifically designed for patient use to monitor urine pH. The authors usually recommend checking urine pH 3 times per day and then adjusting oral alkalinization and retesting until the daily urinary pH is in the desired range. Testing can then be reduced to once per day or even less depending on the individual’s daily variation.

For patient education information, see Gout.