Hyperuricosuria and Gouty Diathesis Clinical Presentation

• Acute phase

  • Pain symptoms are as follows:
    • As with many other stone types, patients with uric acid–related urinary calculi may present with acute renal or ureteral colic.
    • A typical episode occurs suddenly during the night. The episode is abrupt and does not resolve with rest or change in position. In contrast to someone with an acute abdomen who is stationary, patients experiencing acute renal colic frequently move in unusual positions in an effort to relieve their severe pain.
    • Some patients may experience a gradual onset of pain, resulting in a dull chronic ache in the flank region. The location of pain varies depending on stone location and may shift from the flank to the anterior abdominal wall, groin, and, eventually, to the ipsilateral testicle or labia.
    • When the stone is lodged in the ureterovesical junction, patients frequently report marked urinary frequency and urgency.
    • The severity of pain is often inversely proportional to the size of the stone. Large renal staghorn calculi rarely result in acute renal colic, as is observed with smaller ureteral stones.
    • The degree and type of pain is not specific to any particular stone composition.
  • GI symptoms include the following:
    • Nausea and vomiting are frequently associated with urolithiasis.
    • Patients may report altered bowel habits, including diarrhea or constipation.
  • Urinary symptoms include the following:
    • Patients with ureteral stones near the bladder often report dysuria, frequency, and urgency. Furthermore, gross hematuria may be observed. Eighty-five percent of patients present with either gross or microscopic hematuria.
    • Some patients may present with an associated urinary tract infection. Rare, severe, gas-forming infections may result in pneumaturia.
    • The vast majority of ureteral stones that pass into the bladder transit the urethra uneventfully. A ureteral stone passed into the bladder rarely causes urinary obstruction; these persons usually report an interrupted stream. Unlike in cats, in whom stones frequently become inspissated in the urethra, resulting in renal failure and/or death, stones rarely become obstructed in the human urethra.
• Chronic phase

  • A history of gout and associated joint disease are important clues in discerning the etiology. The use of probenecid (a known uricosuric agent) in patients with gout may result in hyperuricosuria and increase the risk of uric acid stone formation. Uricosuric agents such as probenecid specifically increase urinary uric acid levels to help decrease hyperuricemia and to reduce gout attacks. When they cause hyperuricosuria or uric acid calculi, alternate therapies for the hyperuricemia should be used.
  • Myeloproliferative disorders, especially in children, may result in hyperuricosuria and associated urinary stones. Furthermore, a massive increase in the endogenous purine pool due to tumor necrosis may result in severe hyperuricosuria, crystalluria, and acute urinary obstruction during chemotherapy for myeloproliferative disorders. In these patients, the rate of uric acid stone formation is approximately 40%, which is much higher than in patients with gout.
  • Obtaining a dietary history is important to help elucidate iatrogenic causes of hyperuricosuria, including an excessive intake of purine-rich foods and excessive weight loss, which result in a catabolic state and increased uric acid production.^[2]
  • A hereditary form of hyperuricemia and hyperuricosuria is Lesch-Nyhan syndrome, which may be associated with urinary calculi. These patients have a deficiency in the enzyme hypoxanthine-guanine phosphoribosyl-transferase. This enzyme catalyzes the salvage pathway of purines and is responsible for the conversion of hypoxanthine to inosinic acid and guanine to guanylic acid. If the enzyme is deficient, low levels of guanylic and inosinic acid occur with a subsequent increase in de novo purine synthesis because these nucleotides modulate purine synthesis by feedback inhibition.
  • Long-standing malaise and lethargy may be an associated symptom of urinary obstruction with or without infection.

• Costovertebral angle tenderness is common during acute renal colic. Abdominal distention and tenderness secondary to ileus may also occur.
• In cases with associated urinary tract infection, fever is common.
• After resolution of the acute stone event, patients may be asymptomatic or may present with physical findings related to the underlying disease. For example, patients with gout may present with chronic joint changes (ie, tophi) due to gouty arthritis.

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 3 factors: (1) urinary pH, (2) uric acid concentration, and (3) urinary volume. Based on these factors, the causes of uric acid stones can be categorized as follows:

• Acidic urine

  • Gouty diathesis
  • Chronic diarrhea
  • Inflammatory bowel disease
  • Exercise/dehydration
  • Familial
• Hyperuricosuria

  • Gouty diathesis
  • An excessively purine-rich diet
  • Inborn errors of metabolism
    • Hypoxanthine-guanine phosphoribosyl-transferase deficiency
    • Phosphoribosylpyrophosphate synthetase overactivity
    • Glucose-6-phosphatase synthetase deficiency
  • Myeloproliferative disorders
    • Leukemia
    • Hemolytic anemia
    • Neoplasia
  • Medications
  • Chemotherapy
• Low urinary volume

  • GI disorders
  • Strenuous exercise/dehydration