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Enzymatic conversion of blood group B kidney prevents hyperacute antibody-mediated injuries in ABO-incompatible transplantation.

Nature communications2025-02-11PubMed
Total: 82.0Innovation: 9Impact: 9Rigor: 7Citation: 9

Summary

Using α-galactosidase during hypothermic machine perfusion, >95% of B antigens were removed from donor kidneys, preventing antibody-mediated injury in ex vivo ABO-incompatible simulations. A converted B kidney transplanted into an O-type brain-dead recipient survived 63 hours without hyperacute rejection, despite re-expression of B antigens by 48 hours.

Key Findings

  • α-galactosidase treatment during hypothermic perfusion removed >95% of B antigens from kidney endothelium within 3 hours.
  • Ex vivo ABO-incompatible simulation showed enzyme-treated kidneys were protected from antibody-mediated injuries.
  • A converted type B kidney transplanted into a type O brain-dead recipient survived 63 hours without hyperacute rejection; B antigens re-expressed within 48 hours without histologic AMR.

Clinical Implications

If validated, enzyme treatment during machine perfusion could be integrated into transplant workflows to convert incompatible kidneys, potentially reducing rejection risk and obviating intense desensitization. Anesthesiologists and perioperative teams should anticipate perfusion-based organ conditioning protocols.

Why It Matters

This offers a potentially paradigm-shifting, perfusion-based strategy to enable ABO-incompatible kidney transplantation without conventional desensitization. It could expand the donor pool and reduce waiting times.

Limitations

  • Single human feasibility case with short (63-hour) observation; no long-term outcomes.
  • Re-expression of blood group antigens within 48 hours raises durability and immunogenicity questions.

Future Directions

Conduct multi-center clinical trials to assess safety, durability of antigen removal, dosing/kinetics, and applicability to A antigens and other organs under machine perfusion.

Study Information

Study Type
Case report
Research Domain
Treatment
Evidence Level
V - Single-case human feasibility with ex vivo translational validation
Study Design
OTHER