Mechanisms and Targeted Therapeutic Strategies for Inflammation and Renal Fibrosis in Hyperuricemic Nephropathy

Hyperuricemia (HUA) is a growing global health issue driven by economic development and lifestyle changes. Approximately 75% of uric acid in humans is excreted renally. Excess uric acid deposits in renal tissues, promoting tubulointerstitial fibrosis and leading to hyperuricemic nephropathy (HN), which is characterized by urate crystal deposition, chronic interstitial nephritis, and renal fibrosis. The pathogenesis and progression of HN involves dysregulated activation of multiple signaling pathways, including MAPK, Nrf2/HO-1/NQO1, PI3K/AKT, and ASK1/JNK/c-Jun pathways, which facilitate disease progression through the production of pro-inflammatory cytokines and other mediators. Current treatments primarily consist of urate-lowering drugs such as allopurinol, febuxostat, benzbromarone, and probenecid, but their use is constrained by adverse effects including hepatotoxicity, nephrotoxicity, and Stevens-Johnson syndrome. Therefore, targeting inflammatory and fibrotic mechanisms presents a promising therapeutic approach. This review outlines key molecular pathways in HN, discusses contemporary research challenges, and suggests future directions for improved therapeutic strategies.