Recombinant apoptosis inhibitor of macrophage protein reduces delayed graft function in a murine model of kidney transplantation

PLoS One. 2021 Apr 23;16(4):e0249838. doi: 10.1371/journal.pone.0249838. eCollection 2021.


Reperfusion injury following cold and warm ischemia (IRI) is unavoidable during kidney transplantation and contributes to delayed graft function (DGF) and premature graft loss. Death of tubular epithelial cells (TECs) by necrosis during IRI releases pro-inflammatory mediators (e.g. HMGB1), propagating further inflammation (necroinflammation) and tissue damage. Kidney Injury Molecule-1 (KIM-1) is a phagocytic receptor upregulated on proximal TECs during acute kidney injury. We have previously shown that renal KIM-1 protects the graft against transplant associated IRI by enabling TECs to clear apoptotic and necrotic cells, and that recognition of necrotic cells by KIM-1 is augmented in the presence of the opsonin, apoptosis inhibitor of macrophages (AIM). Here, we tested whether recombinant AIM (rAIM) could be used to mitigate transplant associated IRI. We administered rAIM or vehicle control to nephrectomised B6 mice transplanted with a single B6 donor kidney. Compared to grafts in vehicle-treated recipients, grafts from rAIM-treated mice exhibited significantly less renal dysfunction, tubular cell death, tissue damage, tubular obstruction, as well as local and systemic inflammation. Both mouse and human rAIM enhanced the clearance of necrotic cells by murine and human TECs, respectively in vitro. These data support testing of rAIM as a potential therapeutic agent to reduce DGF following kidney transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / administration & dosage
  • Apoptosis Regulatory Proteins / therapeutic use*
  • Cells, Cultured
  • Delayed Graft Function / drug therapy*
  • Delayed Graft Function / prevention & control
  • HEK293 Cells
  • Humans
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / methods
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Scavenger / administration & dosage
  • Receptors, Scavenger / therapeutic use*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use


  • Apoptosis Regulatory Proteins
  • CD5L protein, human
  • Receptors, Scavenger
  • Recombinant Proteins

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