2.1.1. Donor Biological Fluids

Elevated donor plasma mitochondrial DNA levels independently predicted DGF and correlated with 1-year graft survival in a cohort of DCD [10].

Following organ procurement, the role of innate immune system, such as Complement in IRI, has been extensively investigated. By generating effector molecules (C4b, C4d, C3b, iC3b, C3dg, and C3d) and anaphylatoxins (C3a, C5a), Complement can recruit granulocytes, monocytes, and other inflammatory cells to the site of ischemic injury and regulate activation of tubular epithelial cells and pericytes within the kidney. In addition, Complement factors can directly damage renal parenchymal cells by inducing tubular apoptosis, endothelial-to-mesenchymal transition (EndMT), pericytes-to-mesenchymal transition, and accelerated senescence [28–31]. EndMT deeply modifies endothelial cells, which acquires a mesenchymal phenotype and new properties, such as capacity to produce extracellular matrix (EM) and induce fibrosis. Biomarkers of EndMT have been the focus of recent research in different KTx areas and will be discussed in detail in following sections on recipient-related DGF biomarkers (Section 2.2.4) and on chronic rejection-IFTA within the setting of CAD (Section 4.1.3).

Consistently, donor urinary C5a levels were independently associated with recipient post-transplant DGF, providing a potential rationale for complement-blocking therapies to prevent DGF in high risk patients [11].
