From the Guidelines
Uric acid levels should be maintained below 6.0 mg/dL for most people, with lower targets (under 5.0 mg/dL) for those with severe gout, tophi, or chronic arthropathy, as recommended by the 2020 American College of Rheumatology guideline for the management of gout 1.
Key Recommendations
- For patients with gout, the target uric acid level should be below 6.0 mg/dL, with a lower target of under 5.0 mg/dL for those with severe gout, tophi, or chronic arthropathy.
- Medications like allopurinol (starting at 100mg daily, gradually increasing to 300-600mg as needed) or febuxostat (40-80mg daily) can effectively lower uric acid, as stated in the 2016 updated EULAR evidence-based recommendations for the management of gout 1.
- Lifestyle modifications are equally important, including:
- Reducing intake of purine-rich foods (organ meats, shellfish, red meat)
- Limiting alcohol (especially beer)
- Avoiding high-fructose corn syrup
- Maintaining a healthy weight
- Staying well-hydrated with at least 2-3 liters of water daily
Monitoring and Management
- Regular monitoring of uric acid levels every 2-4 weeks during medication adjustment and then every 6 months thereafter ensures proper management, as recommended by the 2017 EULAR evidence-based recommendations for the management of gout 1.
- During acute gout attacks, anti-inflammatory medications like colchicine, NSAIDs, or corticosteroids are recommended, but uric acid-lowering therapy should continue.
- Elevated uric acid occurs when the body either produces too much uric acid or the kidneys cannot efficiently excrete it, leading to hyperuricemia, which can cause gout, kidney stones, and is associated with metabolic syndrome.
Important Considerations
- The 2020 American College of Rheumatology guideline for the management of gout recommends a treat-to-target strategy, maintaining the SUA level <6 mg/dL, which is below the saturation point for MSU to dissolve all crystal deposits 1.
- The task force recommends upward titration of ULT in every patient when feasible, which might result in fewer episodes of acute flares during treatment initiation and therefore improved adherence to ULT, as stated in the 2017 EULAR evidence-based recommendations for the management of gout 1.
From the FDA Drug Label
As a result of xanthine oxidase inhibition, the serum concentration of hypoxanthine plus xanthine in patients receiving allopurinol tablets for treatment of hyperuricemia is usually in the range of 0.3 to 0.4 mg/dL compared to a normal level of approximately 0.15 mg/dL. Administration of allopurinol tablets generally results in a fall in both serum and urinary uric acid within 2 to 3 days. The degree of this decrease can be manipulated almost at will since it is dose-dependent Allopurinol tablets reduce both the serum and urinary uric acid levels by inhibiting the formation of uric acid
The normal uric acid level is not explicitly stated in the provided text, but it can be inferred that the goal of allopurinol treatment is to reduce the serum uric acid level below the saturation point to suppress urate precipitation.
- The saturation point is not explicitly defined in the text, but it is mentioned that urate precipitation is expected to occur above 7 mg/dL of oxypurines.
- The effect of allopurinol on uric acid levels is a decrease in both serum and urinary uric acid within 2 to 3 days, with the degree of decrease being dose-dependent 2.
From the Research
Uric Acid Level Management
- The management of uric acid levels is crucial in the treatment of gout, with a target serum urate concentration of less than 6 mg/dL 3, 4, 5.
- Febuxostat and allopurinol are two commonly used urate-lowering therapies (ULTs) for treating gout, with febuxostat being more effective in achieving serum urate goals in some studies 3, 4, 5.
- A systematic review and meta-analysis found that 70.7% of patients reached the target serum urate level with febuxostat therapy, compared to 44.4% with allopurinol 4.
Comparative Effectiveness of Allopurinol and Febuxostat
- A double-blind noninferiority trial found that allopurinol was noninferior to febuxostat in controlling flares, with similar outcomes in participants with stage 3 chronic kidney disease 6.
- Another study found that febuxostat was significantly more effective in patients reaching serum urate goals, with an adjusted odds ratio of 1.73 (95% CI, 1.48-2.01) 3.
- The choice between allopurinol and febuxostat may depend on individual patient factors, such as renal function and comorbidities 3, 4, 6.
Uric Acid and Hypertension
- High uric acid levels have been linked to an increased risk of hypertension, with xanthine oxidase-related oxidative stress potentially inducing endothelial dysfunction and renal vasoconstriction 7.
- Lifestyle changes to maintain uric acid levels within the normal range are recommended, particularly in young (pre)hypertensive individuals or normotensives with a family history of hypertension, metabolic disorders, or obesity 7.