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Kidney Week

Abstract: PO2452

Remdesivir Inhibits Tubulointerstitial Fibrosis in Obstructed Kidneys

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Xu, Lin, Shuguang Hospital, Shanghai, China
  • Wu, Ming, Shuguang Hospital, Shanghai, China
  • Ye, Chaoyang, Shuguang Hospital, Shanghai, China
Background

Kidney impairment is observed in patients with COVID-19. The effect of anti-COVID-19 agent remdesivir on kidneys is currently unknown. We aimed to determine the effect of remdesivir on renal fibrosis and its downstream mechanisms.

Methods

Remdesivir and its active nucleoside metabolite GS-441524 were used to treat TGF-β stimulated renal fibroblasts (NRK-49F) and human renal epithelial (HK2) cells. Vehicle or remdesivir were given by intraperitoneal injection or renal injection through the left ureter in unilateral ureteral obstruction (UUO) mice. Serum and kidneys were harvested. The concentrations of remdesivir and GS-441524 were measured using LC-MS/MS. Renal and liver function were assessed. Renal fibrosis was evaluated by Masson's trichrome staining and Western blotting.

Results

Remdesivir and GS-441524 inhibited the expression of fibrotic markers (fibronectin and aSMA) in NRK-49F and HK2 cells. Intraperitoneal injection or renal injection of remdesivir attenuated renal fibrosis in UUO kidneys. Renal and liver function were unchanged in remdesivir treated UUO mice. Two remdesivir metabolites were detected after injection. Phosphorylation of Smad3 that was enhanced in cell and animal models for renal fibrosis was attenuated by remdesivir. In addition, the expression of Smad7, an anti-fibrotic factor, was increased after remdesivir treatment in vitro and in vivo.

Conclusion

Remdesivir inhibits renal fibrosis in obstructed kidneys.

Funding

  • Government Support – Non-U.S.