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

Area of Science:

• Nephrology
• Immunology
• Transplantation

Background:

• Long-term outcomes regarding T-cell-mediated rejection (TCMR) after kidney transplantation with anti-cluster of differentiation (CD)25 induction are not well understood.
• The impact of maintenance immunosuppression with tacrolimus, mycophenolate mofetil (MMF), or prednisone on TCMR is also unclear.

Purpose of the Study:

• To investigate the risk factors and long-term impact of TCMR in kidney transplant recipients.
• To evaluate the frequency, types, and consequences of TCMR on kidney function and graft survival.
• To identify predictors of TCMR in this patient population.

Main Methods:

• Retrospective analysis of a single-center cohort of 2024 kidney transplant recipients (2010-2020) with follow-up until June 2025.
• Evaluation of TCMR incidence, Banff classification, kidney function (eGFR), and graft loss.
• Assessment of risk factors including pretransplant donor-specific anti-human leukocyte antigen (preDSA) antibodies.

Main Results:

• The cumulative incidence of acute TCMR was 15% in recipients without preDSA, associated with lower eGFR and 3% TCMR-related graft loss at 10 years.
• TCMR incidence increased with younger recipient age, deceased donor kidneys, and more HLA mismatches.
• Pre-existing donor-specific antibodies (preDSA), particularly against HLA class II, significantly elevated TCMR rates (28% vs. 13%) and graft loss (7% vs. 0.8% at 1 year).

Conclusions:

• Anti-CD25 induction with standard maintenance immunosuppression offers protection against TCMR-related graft loss.
• Kidney transplant recipients with pre-existing donor-specific antibodies against HLA class II represent a high-risk group for TCMR and subsequent graft loss.
• Risk stratification and tailored immunosuppression strategies are crucial for patients with preDSA.