Sensitivity of Serum Urate in Acute Gout
Serum urate has poor sensitivity for diagnosing acute gout, with 32-40% of patients presenting with normal levels (<6.8 mg/dL) during an acute attack, making it an unreliable diagnostic test during flares. 1, 2
Why Serum Urate Fails During Acute Attacks
Serum uric acid behaves as a negative acute-phase reactant, temporarily decreasing during acute inflammation, which explains why many patients have paradoxically normal levels during their most symptomatic periods. 3
In the largest clinical trials of acute gout treatment (n=339 patients), 14% had truly normal serum urate (≤6 mg/dL) and 32% had levels ≤8 mg/dL during documented acute gout attacks. 2
A retrospective study found that 39.8% of gout patients had normouricemia during an acute attack, with higher inflammatory markers (elevated ESR and CRP) correlating with lower uric acid levels. 4
Another study demonstrated that 63.3% of patients with acute gout attacks had normal serum uric acid levels, with increased urinary excretion of uric acid found in 55% of those tested. 5
Mechanism of Decreased Levels During Attacks
Increased renal excretion is the primary mechanism: During acute attacks, clearance of uric acid and fractional excretion of uric acid (FEur) are notably increased, especially in patients with serum urate <420 μmol/L (7 mg/dL). 6
The inflammatory response during acute gout triggers enhanced urinary uric acid excretion, which can lower serum levels below the diagnostic threshold even in patients with chronic hyperuricemia. 6
Guideline-Based Diagnostic Approach
The American College of Physicians explicitly states that serum uric acid levels do not confirm or exclude gout during acute attacks because many patients have normal levels during flares, and hyperuricemia alone does not equal gout. 1
The European League Against Rheumatism emphasizes that serum urate levels during acute attacks are unreliable for diagnosis, as many people with hyperuricemia never develop gout while patients with crystal-proven gout may have normal serum levels during flares. 3
Demonstration of monosodium urate crystals in synovial fluid or tophus aspirates permits definitive diagnosis, not serum urate levels (strength of recommendation 96,95% CI 93-100). 3
Clinical Implications
Do not exclude gout based on normal serum urate during an acute attack—the diagnosis should be based on clinical features, response to colchicine, and ideally crystal identification. 5
Check baseline urate levels AFTER the acute attack has resolved to assess the need for urate-lowering therapy, not during the attack for diagnostic purposes. 1
Patients taking chronic allopurinol are even more likely to have lower serum urate at baseline during acute attacks (mean 7.1 vs 8.5 mg/dL in non-users, p<0.001), further reducing diagnostic sensitivity. 2
When to Use Serum Urate Monitoring
Serum urate monitoring is valuable for managing chronic gout and guiding urate-lowering therapy, but NOT for diagnosing acute attacks. 1
During chronic management, monitor urate levels to ensure therapeutic targets are achieved (<6 mg/dL for most patients, <5 mg/dL for severe disease with tophi). 1
Patients achieving serum urate <6.0 mg/dL at 1 year have approximately 5% risk of acute attacks, versus 10-15% risk for those ≥6.0 mg/dL. 1