Tigulixostat Alleviates Hyperuricemic Nephropathy by Promoting M2 Macrophage Polarization.

PURPOSE

Serum uric acid (SUA) is primarily produced through the hydrolysis of purines in the liver, with its excretion largely handled by the kidneys. Urate transporter 1 (URAT1) inhibitors are known to enhance uric acid elimination via the kidneys, but they also increase the risk of kidney stone formation. Currently, xanthine oxidase (XO) inhibitors are the predominant uric-lowering medications on the market.

METHODS

In this study, we utilized single-cell RNA sequencing, spatial metabolomics, plasma metabolomics, flow cytometry to explore the effects of Tigulixostat on uric acid level and hyperuricemic nephropathy (HN) in Uox-KO mouse model.

RESULTS

In this study, we discovered that Tigulixostat (LC350189) more effectively reduced SUA levels and resulted in better renal outcomes compared to allopurinol, without inducing liver injury in urate oxidase knockout (Uox-KO) mice. Mechanistically, we found that Tigulixostat improved HN by promoting M2 macrophage polarization.

CONCLUSION

These findings suggest Tigulixostat as a promising therapeutic option for managing hyperuricemia and related kidney conditions.