CD4- and CD8-to-Total Lymphocyte Ratios to Guide Rabbit Anti-Thymocyte Globulin Induction in Kidney Transplant Recipients: A Single-Center Feasibility Study.

Abstract

Aim: Rabbit anti-thymocyte globulin (rATG) is widely used for induction immunosuppression in kidney transplantation, but conventional dosing is largely weight based and may not reflect dynamic interindividual immune responses. We aimed to evaluate a predefined, individualized dosing strategy guided by peripheral CD4-to-total lymphocyte (CD4/TLC) and CD8-to-total lymphocyte (CD8/TLC) ratios and to assess its feasibility and 1-year outcomes.

Methods: In this single-center retrospective cohort study conducted in Taiwan from 2018 to 2024, 76 adult kidney transplant recipients received rATG titrated by serial flow cytometry to a predefined target of both CD4/TLC and CD8/TLC ratios < 10%. We evaluated cumulative rATG exposure, lymphocyte-subset response, for-cause biopsy-proven acute rejection (BPAR), graft function, graft loss, hospitalization-requiring infections, and mortality over 1 year.

Results: The median cumulative rATG dose was 1.2 mg/kg (IQR, 1.1-1.5; maximum, 3.8). Thirty-eight recipients (50.0%) reached the immunologic target after a single intraoperative dose (1-1.5 mg/kg). At 1 year, for-cause BPAR occurred in 1 recipient (1.3%), mean serum creatinine was 1.20 mg/dL, and no graft loss occurred. Seventeen recipients experienced hospitalization-requiring infections, accounting for 22 episodes. No CMV disease or biopsy-proven BK virus nephropathy was observed. Four recipients (5.3%) died, including two deaths related to opportunistic fungal infections.

Conclusion: CD4/TLC- and CD8/TLC-guided rATG dosing was feasible and achieved predefined immunologic targets with low cumulative rATG exposure in this cohort. These findings support prospective controlled studies to evaluate the clinical utility, safety, and comparative effectiveness of this individualized dosing strategy.