The role of neutrophil extracellular trap formation in kidney transplantation: Implications from donors to the recipient

Abstract

Kidney transplantation remains the gold standard for patients with end-stage renal disease, but severe donor organ shortage has led to long waiting lists. The utilization of expanded criteria donor kidneys within the category of deceased donors has enlarged the pool of available kidneys for transplantation; however, these grafts often have an increased risk for delayed graft function or reduced graft survival following transplantation. During brain or circulatory death, neutrophils are recruited to the vascular beds of kidneys where a proinflammatory microenvironment might prime the formation of neutrophil extracellular traps (NETs), web-like structures, containing proteolytic enzymes, DNA, and histones. NETs are known to cause tissue damage and specifically endothelial damage while activating other systems such as coagulation and complement, contributing to tissue injury and an unfavorable prognosis in various diseases. In lung transplantation and kidney transplantation studies, NETs have also been associated with primary graft dysfunction or rejection. In this review, the role that NETs might play across the different phases of transplantation, already initiated in the donor, during preservation, and in the recipient, will be discussed. Based on current knowledge, NETs might be a promising therapeutic target to improve graft outcomes.

Keywords: DAMPs; complement; donor; endothelial activation; innate immunity; kidney transplantation; machine perfusion; neutrophil extracellular traps; platelets; rejection.