Sleeve gastrectomy ameliorates renal injury in obesity-combined hyperuricemic nephropathy mice by modulating the AMPK/Nrf2/ABCG2 pathway.

Hyperuricemic nephropathy (HN) is renal injury caused by hyperuricemia (HUA). While sleeve gastrectomy (SG) has shown promise in improving renal injury in patients with obesity-related HN, the mechanisms are not fully understood. This study induced an obesity-combined HN model in male ob/ob mice and measured serum uric acid (SUA), creatinine, and other biochemical indicators 6 weeks post-surgery. Renal histological changes were evaluated through staining techniques, and the study also assessed renal adenosine monophosphate-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation levels and urate transporter ABCG2 expression. In vitro experiments involved Nrf2 knockdown in AMPK-activated HK-2 cells and ChIP to confirm Nrf2 binding to the ABCG2 promoter. Results showed that SG reduced SUA levels, serum creatinine, and blood urea nitrogen, increased p-AMPK, p-Nrf2 protein, and ABCG2 expression, and alleviated renal fibrosis and inflammation. In vitro, Nrf2 knockdown down-regulated ABCG2 expression, and ChIP confirmed Nrf2's role in ABCG2 transcription. The study suggests that SG may improve renal injury in HN mice by modulating the AMPK/Nrf2 pathway and upregulating ABCG2 transcription.