Rescue RM/CS-AKI by blocking strategy with one-dose anti-myoglobin RabMAb

Xinyue Wang, Ning Li (), Lu Han, Ou Qiao, Xin Chen, Pengtao Wang, Lancao Zhang, Yingjie Hou, Fengjiao Bao, Herui Hao, Sania Saeed, Li Zhang, Zizheng Li, Xiaohong Duan, Shuquan Rao (), Zichuan Liu () and Yanhua Gong ()
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Xinyue Wang: Tianjin University
Ning Li: Tianjin University
Lu Han: Chinese Academy of Medical Sciences & Peking Union Medical College
Ou Qiao: Tianjin University
Xin Chen: Tianjin University
Pengtao Wang: Tianjin First Center Hospital
Lancao Zhang: Tianjin University
Yingjie Hou: Tianjin University
Fengjiao Bao: Tianjin University
Herui Hao: Tianjin University
Sania Saeed: Tianjin University
Li Zhang: Tianjin University
Zizheng Li: Tianjin University
Xiaohong Duan: Tianjin University
Shuquan Rao: Chinese Academy of Medical Sciences & Peking Union Medical College
Zichuan Liu: Tianjin University
Yanhua Gong: Tianjin University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Rhabdomyolysis or Crush syndrome-related AKI (RM/CS-AKI) has high mortality, and there is no effective early on-site treatment method. The critical pathogenic factor of RM/CS-AKI is the excessive free myoglobin (Mb) in blood circulation. Here, based on the concept of creating a “mobile barrier”, we develop an anti-Mb rabbit monoclonal antibody (RabMAb) with high specificity, affinity, stability, and broad species reactivity. A single dose of anti-Mb RabMAb injection is sufficient for emergency rescue in both homologous and heterologous RM/CS-AKI male animal models. The main goal of blocking the passage of free Mb through the glomerular filtration barrier has been achieved by using the anti-Mb RabMAb, which has a long-term stable therapeutic effect within 14 days and promotes phagocytosis of Mb. The optimal administration strategy, pharmacokinetic analysis, toxicity evaluation for anti-Mb RabMAb, and the distribution of its immune complexes in RM/CS-AKI mice are investigated. Thus, we develop effective prevention and control strategies for RM/CS-AKI.

Date: 2025
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DOI: 10.1038/s41467-025-56353-4

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