Reappraisal of Risk Factors for T-Cell-Mediated Kidney Rejection

The risk factors for and the impact of T-cell-mediated rejection (TCMR) in the long term after kidney transplantation in recipients receiving anti-cluster of differentiation (CD)25 induction, followed by tacrolimus or mycophenolate mofetil (MMF) or prednisone maintenance is unknown.

A single center cohort of 2024 kidney transplant recipients between 2010 and 2020 with follow-up until June 2025 was analyzed retrospectively for frequency and type of TCMR, impact on kidney function, and graft loss. Potential risk factors for TCMR were evaluated.

The cumulative incidence of acute TCMR in the group without pretransplant donor-specific anti-human leukocyte antigen (HLA) antibodies (preDSA) (n = 1733, 86% of cohort) was 15% (4% borderline TCMR [bTCMR], 2% Banff TCMR grade 1, 7% Banff TCMR grade 2 and 3, and 2% mixed type rejection) after a median follow-up of 7 years. TCMR was associated with a lower estimated glomerular filtration rate (eGFR) at 1 year (43 ml/min per 1.73 m² vs. 52 ml/min per 1.73 m², P < 0.001), and TCMR-related graft loss at 10-year follow-up was 3%. Increasing incidence of TCMR was associated with younger age recipients, deceased donor (DD) kidney, and higher number of HLA mismatches. The presence of preDSA (n = 291, 14% of cohort) substantially increased the incidence of all types of TCMR (28% at 1 year for preDSA vs. 13% for no preDSA, P < 0.001) and TCMR-related graft loss (7% vs. 0.8% at 1 year, P < 0.001). This effect was mainly driven by the subgroup of recipients with preDSA against HLA class II.

An immune suppressive regime of anti-CD25 induction and tacrolimus or MMF or prednisone maintenance is associated with a low risk of TCMR-related graft loss except for recipients with preDSA against HLA class II.