*Purpose: Pre-transplant indices capable of predicting long-term renal allograft function could improve graft allocation strategies. We previously associated pretransplant frequency of Tumor Necrosis Factor Receptor 2 (TNFR2) expressing circulating T-regulatory cells (Treg) with short term renal allograft function. TNFR2 expression is associated with Treg anti-inflammatory function and strongly predicted immediate graft function in kidney transplantation. This study aims to characterize long-term outcomes in this cohort based on pretransplant Treg TNFR2 expression.

*Methods: Adult deceased donor renal transplant recipients (n=76) performed at a single center between 2011 and 2014 were recruited in a previous prospective study of pre-transplant Treg functional measures and their impact on short term outcomes. We conducted a 10-year update of this cohort. Seventy-two of 76 recipients were included, as 4 were lost to follow-up. Outcomes in the present analysis include: graft status, cause of failure, biopsy-proven rejection, de novo donor specific antibody (DSA) detection, death, graft status at death. Multivariate analysis was performed with: delayed graft function, acute kidney injury (slow and delayed graft function), donor age, cold ischemia time, and expanded criteria donor. TNFR2 grouping was based on an optimal cut-off value of 4.27% as determined in the previous receiver operating characteristic curve analysis, which was repeated to validate it for 10-year graft and patient survival.

*Results: Recipients with high TNFR2⁺Treg frequency prior to transplant had better 5-year death censored graft survival (97% vs. 78%, p=0.024) and better 10-year patient and death censored graft survival (75% vs. 42%, p=0.012; 81% vs. 58%, p=0.02 respectively). A lower rate of de novo DSA production was observed in the high-TNFR2 group (0% vs. 14.3%, X²=4.67, p=0.03). No statistically significant association was seen between TNFR2 expression and acute rejection. Multivariate analysis demonstrated that higher pre-transplant TNFR2⁺Treg frequency was associated with increased long term survival (OR 3.75, 95%CI 1.19-11.71, p=0.02). Treg TNFR2 expression was not associated with body mass index or diabetes mellitus status.

*Conclusions: Higher TNFR2⁺Treg frequency pretransplant is associated with lower incidence of de novo DSA and higher long-term graft and patient survival. This may improve risk stratification in kidney transplant candidates and lead to mechanistic insights for improving long-term outcomes.

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