Enzyme-converted O kidneys allow ABO-incompatible transplantation without hyperacute rejection in a human decedent...

Area of Science:

• Nephrology
• Transplantation Immunology
• Organ Engineering

Background:

• ABO-incompatible kidney transplantation is crucial for organ supply but faces challenges with current recipient desensitization protocols.
• Plasmapheresis-based protocols increase infection, bleeding risks, and healthcare costs.
• A need exists for safer, more accessible strategies for ABO-incompatible kidney transplants.

Purpose of the Study:

• To develop and evaluate a donor-centric desensitization protocol for ABO-incompatible kidney transplantation.
• To assess the efficacy of enzymatic A antigen removal from donor kidneys.
• To investigate the potential for improved organ allocation and patient outcomes.

Main Methods:

• Developed a donor-centric protocol to convert type-A kidneys into type-O kidneys using enzymatic A antigen removal during hypothermic perfusion.
• Validated the ex vivo model for absence of antibody-mediated injury.
• Transplanted an enzyme-converted O kidney into a type-O recipient with high anti-A antibody titers.
• Monitored graft tolerance, antibody-mediated rejection, A-antigen regeneration, and immune response via Banff scores and single-cell sequencing.

Main Results:

• Ex vivo model showed no antibody-mediated injury.
• Transplanted kidney showed no hyperacute rejection and was well tolerated for 2 days.
• Antibody-mediated lesions and complement deposition emerged by day 3, coinciding with A-antigen regeneration.
• Elevated expression of accommodation-related genes was observed, suggesting potential for tolerance.

Conclusions:

• Enzymatic conversion of donor kidneys offers a promising donor-centric strategy for ABO-incompatible transplantation.
• A-antigen regeneration necessitates further research for long-term graft survival.
• This approach has the potential to expand access to kidney transplantation and improve organ allocation equity.