Description

Lesinurad is a selective uric acid reabsorption inhibitor that works by blocking URAT1, a transporter responsible for uric acid reabsorption in the kidneys. It is approved for use in combination with a xanthine oxidase inhibitor for patients who have not achieved target serum urate levels with a xanthine oxidase inhibitor alone. The CLEAR 1 and CLEAR 2 trials (Saag et al., 2017) demonstrated that lesinurad in combination with allopurinol significantly increased the proportion of patients achieving target serum urate levels compared to allopurinol alone. However, lesinurad has been associated with an increased risk of renal adverse events, particularly when used without a xanthine oxidase inhibitor. A pooled safety analysis by Terkeltaub et al. (2019) confirmed these findings but showed that the risk was mitigated when lesinurad was used as indicated in combination with a xanthine oxidase inhibitor. Due to these safety concerns, lesinurad is typically reserved for patients who have not achieved adequate response with other urate-lowering therapies.