What are the implications of asymptomatic hyperuricemia (elevated uric acid)?

From the Guidelines

Asymptomatic elevated uric acid does not require medication treatment unless uric acid levels are extremely high or there are other risk factors present, and lifestyle modifications are the recommended first approach. For most patients with asymptomatic hyperuricemia, the following lifestyle modifications are recommended:

• Maintaining a healthy weight
• Limiting alcohol consumption (especially beer)
• Reducing intake of purine-rich foods (such as red meat, organ meats, and seafood like anchovies and sardines)
• Staying well-hydrated Regular monitoring of uric acid levels every 6-12 months is advisable 1. If uric acid levels exceed 9 mg/dL or if the patient has comorbidities like chronic kidney disease, cardiovascular disease, or a strong family history of gout, medication might be considered 1. In such cases, allopurinol starting at 100 mg daily and gradually increasing to 300 mg daily is typically the first-line treatment. Febuxostat (40-80 mg daily) is an alternative for those who cannot tolerate allopurinol. The rationale for conservative management of asymptomatic hyperuricemia is that many people with elevated uric acid never develop gout or kidney stones, and the benefits of medication must be weighed against potential side effects, including rare but serious hypersensitivity reactions with allopurinol 1.

According to the 2020 American College of Rheumatology guideline for the management of gout, initiating ULT is conditionally recommended against in patients with asymptomatic hyperuricemia, unless there are specific conditions such as comorbid moderate-to-severe CKD (stage ≥3), SU concentration >9 mg/dl, or urolithiasis 1. The guideline emphasizes the importance of shared decision-making and considering individual patient characteristics and preferences when deciding on treatment.

In terms of specific treatment recommendations, the guideline suggests that allopurinol and febuxostat can provide benefit for patients with asymptomatic hyperuricemia and comorbidities such as CKD or urolithiasis 1. However, the decision to initiate ULT should be made on a case-by-case basis, taking into account the potential benefits and risks of treatment.

Overall, the management of asymptomatic elevated uric acid should prioritize lifestyle modifications and regular monitoring, with medication treatment considered only in cases where there are specific risk factors or comorbidities present.

From the Research

Asymptomatic Elevated Uric Acid

• Asymptomatic hyperuricemia is a condition where serum uric acid levels are elevated without any symptoms, and its treatment is still a topic of debate 2, 3, 4, 5, 6.
• The current guidelines do not recommend treating asymptomatic hyperuricemia, unless the patient has very high levels of uric acid or is at risk of complications such as gout, urolithiasis, or uric acid nephropathy 3.
• Some studies suggest that urate-lowering therapy (ULT) may be beneficial in reducing composite renal events and improving renal function in patients with asymptomatic hyperuricemia 4.
• However, other studies have found that ULT has minimal impact on cardiovascular events in patients with gout, and its use in asymptomatic hyperuricemia associated with cardiovascular diseases does not warrant a clear benefit 5, 6.
• The management of asymptomatic hyperuricemia should involve regular assessment of uric acid and clinical symptoms before starting and renewing a urate-lowering treatment 5, 6.
• Allopurinol is often prescribed for asymptomatic hyperuricemia, but its use is not backed by conclusive evidence from prospective randomized controlled trials, and its potential benefits must be weighed against its potential for harm 6.

Urate-Lowering Agents

• Urate-lowering agents, such as allopurinol and febuxostat, have been shown to be effective in reducing composite renal events and improving renal function in patients with asymptomatic hyperuricemia 4.
• However, the use of these agents in asymptomatic hyperuricemia associated with cardiovascular diseases does not warrant a clear benefit, and their potential benefits must be weighed against their potential for harm 5, 6.
• Other urate-lowering agents, such as probenecid, benzbromarone, sulfinpyrazone, rasburicase, lesinurad, and topiroxostat, have also been studied, but their efficacy and safety in asymptomatic hyperuricemia are not well established 4.

Cardiovascular Risk

• Asymptomatic hyperuricemia has been associated with an increased risk of cardiovascular disease, but whether elevated uric acid is a causal agent and thus a possible therapeutic target is still uncertain 5.
• Addressing cardiovascular issues with guideline-recommended therapies may lower uric acid and reduce the occurrence of cardiovascular events, but the use of direct-acting urate-lowering agents in asymptomatic hyperuricemia associated with cardiovascular diseases does not warrant a clear benefit 5.