What are the management options for hypouricemia?

Management of Hypouricemia

In most cases of hypouricemia, no specific treatment is required beyond identifying and addressing the underlying cause, as hypouricemia itself is generally benign unless associated with specific complications like exercise-induced acute kidney injury or nephrolithiasis. 1, 2

Initial Diagnostic Approach

The first step is determining whether hypouricemia (serum uric acid <2.0 mg/dL or 119 μmol/L) is drug-induced or due to an underlying condition 1, 3:

Medication Review

• Discontinue or adjust causative medications if clinically appropriate, as drugs account for approximately half of hypouricemia cases 2, 4
• Common culprits include:
  • Urate-lowering therapies (allopurinol, febuxostat, pegloticase) used for gout treatment 1, 4
  • Uricosuric agents (probenecid, benzbromarone, lesinurad) 4
  • Losartan, fenofibrate, high-dose trimethoprim-sulfamethoxazole, NSAIDs, and high-dose salicylates 4

Measure Fractional Excretion of Uric Acid (FEUA)

• Calculate FEUA to differentiate between decreased production versus increased renal excretion 3, 2
• FEUA >10% with hypouricemia suggests renal hypouricemia (defective tubular reabsorption) 3
• Normal or reduced FEUA suggests decreased uric acid production 2

Management Based on Etiology

Drug-Induced Hypouricemia

• If due to overtreatment with urate-lowering therapy, reduce the dose or discontinue temporarily 1
• The 2020 ACR guidelines note concern about prolonged profound hypouricemia (SU ≤3 mg/dL), given epidemiologic associations with neurodegenerative disorders, though causality is unestablished 5
• Avoid targeting serum uric acid levels <3 mg/dL for long-term therapy 6

Hereditary Renal Hypouricemia

• Most patients remain asymptomatic and require only monitoring 3, 7
• Counsel patients to avoid dehydration and extreme exercise, as these can precipitate exercise-induced acute kidney injury 3, 7
• Maintain adequate hydration during physical activity to prevent complications 7
• If acute kidney injury develops post-exercise, employ a "wait-and-see" approach with supportive therapy, as outcomes are typically excellent 7
• Consider genetic testing (SLC22A12 for type 1, SLC2A9 for type 2) to confirm diagnosis 3

Hereditary Xanthinuria

• Monitor for xanthine stones, hematuria, and chronic kidney disease 3
• Maintain high fluid intake to prevent xanthine stone formation 3
• Diagnosis is confirmed by very low serum urate with elevated urinary xanthine 3

Secondary Hypouricemia

• Address the underlying condition (severe liver disease, neoplasia, diabetes, AIDS, SIADH) 2, 4
• Hypouricemia serves as a biomarker requiring deeper clinical investigation 4

Monitoring and Follow-Up

• For asymptomatic hereditary renal hypouricemia, no specific treatment is needed beyond patient education 7
• Monitor for nephrolithiasis development in patients with hereditary causes 3, 2
• Avoid renal biopsy in suspected renal hypouricemia-associated acute kidney injury, as it is invasive, costly, and typically inconclusive 7

Key Clinical Pitfalls

• Do not overlook hypouricemia as merely a laboratory curiosity—it warrants investigation to identify potentially harmful underlying conditions 4
• Recognize that acute renal failure can occur with the combination of severe hypouricemia and oxidant stress (particularly exercise) 2, 7
• Be aware that hereditary renal hypouricemia is underrecognized, with over 100 cases identified in Japan but likely underdiagnosed elsewhere 3