Dataset Information

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

ABSTRACT: We previously reported associations between autoantibodies to the LG3 fragment of perlecan, anti-LG3, and a higher risk of delayed graft function (DGF) in kidney transplant recipients. Here, we aimed to determine whether some factors that modulate ischemia-reperfusion injury (IRI) can modify this association. We performed a retrospective cohort study in kidney transplant recipients in 2 university-affiliated centers. In 687 patients, 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.

SUBMITTER: Mawad H

PROVIDER: S-EPMC9986256 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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

Mawad Habib H Pinard Louis L Medani Samar S Chagnon Miguel M Boucquemont Julie J Turgeon Julie J Dieudé Mélanie M Hamelin Katia K Rimbaud Annie Karakeussian AK Belayachi Ali A Yang Bing B Collette Suzon S Sénécal Lynne L Foster Bethany J BJ Hébert Marie-Josée MJ Cardinal Héloïse H

Transplant international : official journal of the European Society for Organ Transplantation 20230220

We previously reported associations between autoantibodies to the LG3 fragment of perlecan, anti-LG3, and a higher risk of delayed graft function (DGF) in kidney transplant recipients. Here, we aimed to determine whether some factors that modulate ischemia-reperfusion injury (IRI) can modify this association. We performed a retrospective cohort study in kidney transplant recipients in 2 university-affiliated centers. In 687 patients, we show that high pre-transplant anti-LG3 are associated with ...[more]

PMID: 36891519

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Project description:Background & aimsWhile it is currently assumed that liver assessment is only possible during normothermic machine perfusion, there is uncertainty regarding a reliable and quick prediction of graft injury during ex situ hypothermic oxygenated perfusion (HOPE). We therefore intended to test, in an international liver transplant cohort, recently described mitochondrial injury biomarkers measured during HOPE before liver transplantation.MethodsPerfusate samples of human livers from ten centers in seven countries with HOPE experience were analyzed for released mitochondrial compounds, i.e. flavin mononucleotide (FMN), NADH, purine derivatives and inflammatory markers. Livers deemed unsuitable for transplantation served as negative controls.ResultsWe collected 473 perfusate samples of human donation after cardiac death (n = 315) and donation after brain death (n = 158) livers. Fluorometric assessment of FMN in perfusate was validated by mass spectrometry (R = 0.7011, p <0.0001). Graft loss due to primary non-function or cholangiopathy was predicted by perfusate FMN values (c-statistic mass spectrometry 0.8418, 95% CI 0.7466-0.9370, p <0.0001; c-statistic fluorometry 0.7733, 95% CI 0.7006-0.8461, p <0.0001). Perfusate FMN values were also significantly correlated with symptomatic non-anastomotic strictures and kidney failure, and superior for the prediction of graft loss than conventional scores derived from donor and recipient parameters, such as the donor risk index and the balance of risk score. Mitochondrial FMN values in liver tissues of non-utilized livers were low, and inversely correlated to high perfusate FMN values and purine metabolite release.ConclusionsThis first international study validates the predictive value of the mitochondrial cofactor FMN, released from complex I during HOPE, and may therefore contribute to a better risk stratification of injured livers before implantation.Impact and implicationsAnalysis of 473 perfusates, collected from ten international centers during HOPE (hypothermic oxygenated perfusion), revealed that mitochondria-derived flavin mononucleotide values in perfusate are predictive of graft loss, cholangiopathy, and kidney failure after liver transplantation. This result is of high clinical relevance, as recognition of graft quality is urgently needed to improve the safe utilization of marginal livers. Ex situ machine perfusion approaches, such as HOPE, are therefore likely to increase the number of useable liver grafts.

Dataset Information

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

Publications

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

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