Background: Acute kidney injury (AKI), in both its most severe (delayed graft function, DGF) and milder (slow graft function, SGF) forms, increases the risk for acute rejection and graft loss. Diagnosis is currently made too late after irreversible damage. Recent evidence suggests regulatory T cells (Tregs) attenuate murine AKI. Their implication in AKI after kidney transplantation, however, is unknown. We hypothesized that recipient pre-transplant Treg frequency or function predicts AKI after kidney transplantation.
Methods: Deceased donor kidney transplant recipients (n=53) were divided into AKI (n=37; DGF, n=10; SGF, n=27) and immediate graft function (IGF, n=16) groups based on post-transplant dialysis and 24-hour serum creatinine. Donor, organ procurement, and recipient characteristics were similar between all groups except for donor age and cold ischemic time (CIT). Pre-transplant recipient peripheral blood CD4+CD25hiFoxP3+ Treg frequency was quantified by flow cytometry. Treg function was measured by suppression of autologous CD4+CD25- CFSE-labeled effector T cell proliferation by CD4+CD25+ Treg in vitro.
Results: Pre-transplant Treg suppressive function, but not frequency, was decreased in the DGF, SGF, and AKI in comparison to the IGF recipients (p<0.01; Fig. 1A). When accounting for significantly different variables between our groups (donor age, CIT), a higher Treg function decreased the odds of suffering from DGF in multinomial logistic regression (OR=0.79, p<0.03). Moreover, it predicted AKI in ROC curve analysis (AUC=0.82, p<0.01; Fig. 1B) with a sensitivity of 75% and specificity of 89% at a cut-off value of 13%. This cut-off value also predicted 180-day percent donor renal function recovery in linear regression (B=33.82, p<0.01; Fig. 1C).
Conclusion: Recipient Treg suppressive function, measured pre-transplant and without prior knowledge of donor or organ procurement characteristics, predicts AKI and 180-day renal function recovery. This could guide peri-transplant clinical decisions and lead to novel Treg-targeted therapies for AKI.
To cite this abstract in AMA style:Nguyen M, Sahakian S, Fryml E, Cantarovich M, Liu S, Lipman M, Tchervenkov J, Paraskevas S. Recipient Pre-Operative Regulatory T Cell Function: A Predictor of Acute Kidney Injury after Kidney Transplantation [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/recipient-pre-operative-regulatory-t-cell-function-a-predictor-of-acute-kidney-injury-after-kidney-transplantation/. Accessed April 22, 2021.
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