Treatment of Urate Nephropathy
The primary treatment for urate nephropathy is aggressive hydration, allopurinol for xanthine oxidase inhibition, and urinary alkalinization to prevent intrarenal urate precipitation. 1
Pathophysiology and Diagnosis
- Urate nephropathy occurs when uric acid precipitates in the renal tubules, leading to obstruction and acute kidney injury, particularly in conditions with rapid cell turnover and increased purine metabolism 1
- Diagnosis is based on appropriate clinical setting (increased cell lysis), oliguria, marked hyperuricemia, hyperuricosuria, and a urinary uric acid-to-creatinine ratio greater than 1 1
- Renal function should be measured in all patients with hyperuricemia as part of standard assessment 2
Acute Management
Hydration and Alkalinization
- Aggressive intravenous hydration to maintain high urine output is essential to dilute uric acid concentration in the tubules 1
- Urinary alkalinization (typically with sodium bicarbonate) to maintain urine pH above 6.5 increases uric acid solubility and prevents crystal formation 1
Pharmacological Management
Xanthine Oxidase Inhibitors:
- Allopurinol is the first-line therapy to rapidly reduce uric acid production 2, 3
- Start at low dose (50-100 mg) in patients with renal impairment and titrate upward to achieve target serum urate 4
- Allopurinol inhibits formation of uric acid by blocking xanthine oxidase, reducing both serum and urinary uric acid levels 3
Uricosuric Agents:
- Probenecid may be used as an alternative or adjunct therapy in patients with preserved renal function 2, 5
- Acts by inhibiting tubular reabsorption of urate, increasing urinary excretion of uric acid 5
- Caution: Not recommended as monotherapy in acute urate nephropathy as it may worsen intrarenal urate precipitation initially 1
Renal Replacement Therapy
- Hemodialysis may be required in severe cases to correct azotemia and reduce the body burden of urate 1
- Hemodialysis is preferred over other dialysis modalities as it achieves greater urate clearance 1
Long-term Management
Target Serum Urate Levels
- Maintain serum uric acid below 360 μmol/L (6 mg/dL) to promote crystal dissolution and prevent new crystal formation 2, 4
- In patients with tophi, a more aggressive target of below 300 μmol/L (5 mg/dL) may be appropriate 2
Medication Titration
- Allopurinol should be started at a low dose and gradually increased to achieve target serum urate levels 2, 4
- Doses above 300 mg daily are often necessary to achieve target urate levels 4
- Febuxostat is an alternative for patients who cannot tolerate allopurinol or have renal impairment 2
Monitoring
- Regular monitoring of serum uric acid levels, renal function, and clinical response is essential 4
- Schedule follow-up appointments every 6 months for stable patients 4
Special Considerations
Renal Impairment
- In patients with mild-moderate renal impairment, allopurinol can be used with close monitoring, starting at 50-100 mg daily 2, 4
- Febuxostat and benzbromarone can be used without dose adjustment in renal impairment 2
Tumor Lysis Syndrome
- In patients at risk for tumor lysis syndrome (e.g., those with malignancies undergoing chemotherapy), prophylactic allopurinol should be initiated before cytotoxic therapy 1
- Rasburicase (recombinant uricase) may be considered in severe cases or when allopurinol is insufficient 6
Common Pitfalls to Avoid
- Discontinuing urate-lowering therapy prematurely after achieving symptom control 4
- Relying solely on the standard 300 mg dose of allopurinol, which often fails to achieve target urate levels 4
- Underestimating the need for lifelong therapy based on temporary symptomatic improvement 4
- Failing to provide adequate hydration and urinary alkalinization during acute management 1