Pretransplant Immune Interplay Between Donor and Recipient Influences Posttransplant Kidney Allograft Function

Renal transplant candidates present immune dysregulation caused by chronic uremia, and deceased kidney donors present immune activation induced by brain death. Pretransplant donor and recipient immune-related gene expression were examined in the search for novel predictive biomarkers crosslinking recipient and donor pretransplant immune status with transplant outcome.

This study included 33 low-risk consecutive renal transplant recipients and matched deceased donors. The expression of 29 genes linked to tissue injury, T-cell activation, cell migration, and apoptosis were assessed in postreperfusion kidney biopsies, as well as 14 genes in pretransplant peripheral blood of the kidney recipients. Gene expression was analyzed with real-time polymerase chain reaction on custom-designed low-density arrays.

Donor MMP9 expression was related to delayed graft function occurrence (P = .036) and short term kidney allograft function (14th day r_s = -0.44, P = .012; 1st month r_s = -0.46, P = .013). Donor TGFB1 expression was associated with short- and long-term graft function (14th day r_s = -0.47, P = .007; 3rd month r_s = -0.63, P = .001; 6th month r_s = -0.52, P = .010; 12th month r_s = -0.45, P = .028; 24th month r_s = -0.64, P = .003). Donor TGFB1 expression was not related to donor age (r_s = 0.32, P = .081), which was also an independent factor influencing the outcome. Recipient gene expression was not related to graft function but determined the acute rejection risk. Recipient IFNG and, to a lesser extent, IL18 expression were protective against acute rejection (area under the curve [AUC] 0.84, P < .001, and AUC 0.79, P < .001, respectively).

Kidney transplant outcome depends on the interplay between donor-related immune factors, which mostly affect allograft function and recipient immune milieu, influencing an alloreactive response.