Comment on “Gout: Evaluation and Management”

Abstract

To the Editor,

In the review titled “Gout: Evaluation and Management” presented by Huzmeli (1), the topic is summarized in a comprehensive, clear, and fluent manner. As Huzmeli also highlighted, among urate-lowering treatment (ULT) agents used in the management of hyperuricemia and gout, allopurinol has long served as the first-line treatment. However, in recent years, strong evidence has demonstrated that febuxostat is more effective, particularly in achieving target serum uric acid levels. Furthermore, the renal elimination of allopurinol poses certain limitations in patients with chronic kidney disease (CKD), while the frequency of adverse effects remains a clinical concern. These factors collectively increase the relevance of febuxostat in CKD patients.

Randomized controlled trials such as FACT (2) and APEX (3) have shown that febuxostat achieves target serum uric acid levels at a higher rate than allopurinol in patients both with normal renal function and with CKD. Due to the need for dose reduction of allopurinol in CKD as a result of renal elimination, the use of effective doses may be limited, which can compromise treatment efficacy. In contrast, febuxostat is primarily metabolized hepatically, allowing its administration at therapeutic doses without the need for dose adjustment in patients with impaired renal function. This characteristic is of particular importance in preventing inflammation, crystal deposition, and renal disease progression associated with uric acid accumulation.

On the other hand, although the CARES trial (4) raised concerns regarding a possible association between febuxostat and cardiovascular mortality, the more recent FAST study (5) did not confirm these findings and demonstrated that febuxostat does not increase cardiovascular risk. Therefore, treatment decisions should be individualized based on cardiovascular risk assessment.

In conclusion, current literature indicates that febuxostat provides more effective serum uric acid control than allopurinol, particularly in patients with CKD. When used in appropriate patients with appropriate cardiovascular monitoring, febuxostat should be considered an important therapeutic option in nephrology practice.