Characterising Prognostic Complement Biomarkers During Clinical Normothermic Machine Perfusion for Renal Transplantation.

Complement activation during clinical kidney normothermic machine perfusion (NMP) is poorly defined. We examined whether perfusate complement biomarkers measured during prolonged NMP were associated with early graft recovery. Samples and outcome data were obtained from the NKP1 phase 1 trial of prolonged kidney NMP before transplantation (n=36). Perfusate C1s, collectin-11, C2, C3, C3d, factor B, Ba and soluble C5b-9 were measured at Hour 1 and end perfusion. Associations with functional delayed graft function (fDGF) and time to 50% fall in serum creatinine (TCr50) were assessed using nonparametric testing, Kaplan-Meier analysis and Cox models incorporating UK donor risk index (UKDRI). Paired pre-perfusion and post-reperfusion biopsies underwent multiplex immunofluorescence for C4d, C5b-9 and ICAM-1. C1s, collectin-11, C3d and soluble C5b-9 increased during NMP, whereas C2 and factor B decreased. Kidneys developing fDGF had higher end-perfusion soluble C5b-9 and Hour-1 C3, both significant after false discovery rate correction. Complement profiles stratified TCr50, including within UKDRI strata, and an Hour-1 grouping improved Cox model fit beyond UKDRI alone. Postreperfusion tissue C5b-9 and ICAM-1 increased, whereas C4d did not. Complement activation during prolonged NMP is associated with early graft outcomes and may support biomarker-guided assessment and future targeted intervention in clinical kidney transplantation practice.