Pre-donationstatintherapytoimprovesolidorgantransplantoutcomes

Abstract

Background: Inflammatory injury in organ donors, particularly after brain death and during ischemia-reperfusion, contributes to graft dysfunction, rejection, and reduced survival. Statins, beyond their lipid-lowering role, exert pleiotropic anti-inflammatory and immunomodulatory effects, including IL-6 suppression, NF-κB inhibition, immune cell modulation, and potential alteration of exosome secretion.

Methods: Building upon this background, this narrative review synthesises preclinical and clinical evidence on pre-donation statin therapy in solid organ transplantation. Specifically, we examine mechanistic pathways, such as cytokine signalling, vascular protection, and exosome modulation, alongside clinical data from heart, liver, lung, and kidney transplantation.

Results: In terms of outcomes, preclinical models consistently demonstrate reduced inflammatory burden, preserved microvascular integrity, and improved graft function with donor statin therapy. Moving to clinical studies, limited randomised controlled trials suggest early biochemical and haemodynamic benefits, such as reduced cardiac biomarkers, lower ALT in liver recipients, and reduced primary graft dysfunction in lung recipients. However, evidence for improved long-term graft survival, rejection rates, or mortality is inconsistent. Most trials are underpowered, single-centre, and lack mechanistic endpoint analysis, and data on donation after circulatory death and living donors remain sparse.

Conclusions: Pre-donation statin therapy is biologically plausible, safe in early studies, and supported by robust mechanistic rationale, yet definitive clinical benefit remains unproven. Large, multi-centre trials incorporating mechanistic and clinical endpoints, such as the ongoing SIGNET study, are essential to determine whether this strategy should be integrated into standard donor management.

Keywords: Donor management; Exosomes; Inflammation; Interleukin-6; Ischemia-reperfusion injury; Organ transplantation; Statins.