AUTHOR=Mawad Habib , Pinard Louis , Medani Samar , Chagnon Miguel , Boucquemont Julie , Turgeon Julie , Dieudé Mélanie , Hamelin Katia , Rimbaud Annie Karakeussian , Belayachi Ali , Yang Bing , Collette Suzon , Sénécal Lynne , Foster Bethany J. , Hébert Marie-Josée , Cardinal Héloïse 

TITLE=Hypothermic Perfusion Modifies the Association Between Anti-LG3 Antibodies and Delayed Graft Function in Kidney Recipients

JOURNAL=Transplant International

VOLUME=Volume 36 - 2023

YEAR=2023

URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2023.10749

DOI=10.3389/ti.2023.10749

ISSN=1432-2277

ABSTRACT=We previously reported associations between autoantibodies to the LG3 fragment of perlecan, anti-LG3, and a higher risk of delayed graft function (DGF) and lower 1-year graft function in kidney transplant recipients. Here, we aimed to determine whether some factors that can modulate ischemia-reperfusion injury (IRI) can modify the association between anti-LG3 and DGF. We performed a retrospective cohort study amongst consecutive adult kidney transplant recipients between July 1st, 2008 and December 31st, 2016 in 2 university-affiliated centers. The main outcomes were the occurrence of DGF and graft failure. The main independent variable was pre-transplant anti-LG3 levels. Effect modification by hypothermic perfusion machine and DGF was assessed by including and testing interaction terms in regression models. Multivariable logistic and Fine and Gray proportional subdistribution hazards multivariable regression model for competing-risks were fit for the outcomes of DGF and graft failure respectively. In 687 kidney transplant recipients, we show that high pre-transplant anti-LG3 are associated with DGF when the kidney is transported on ice (odds ratio (OR): 1.75, 95% confidence interval 1.02-3.00), but not when placed on hypothermic perfusion pump (OR: 0.78, 95% CI 0.43-1.37). In patients with DGF, high pre-transplant anti-LG3 are associated with a higher risk of graft failure (subdistribution hazard ratio (SHR): 4.07, 95% CI: 1.80, 9.22), while this was not the case in patients with immediate graft function (SHR: 0.50, 95% CI 0.19, 1.29). High anti-LG3 levels are associated with a higher risk of DGF in kidneys exposed to cold storage, but not when hypothermic pump perfusion is used. High anti-LG3 are also associated with a higher risk of graft failure in patients who experience DGF, a clinical manifestation of severe IRI. Future studies are needed to evaluate hypothermic perfusion to mitigate the impact of IRI on the allograft in patients with high anti-LG3 antibodies.