Immune Monitoring-Guided Individualized Tacrolimus Therapy in Renal Transplant Recipients: An Observational Study and PK/PD Modeling

Immune Monitoring-Guided Individualized Tacrolimus Therapy in Renal Transplant Recipients: An Observational Study and PK/PD Modeling

This study aims to resolve the clinical limitation that therapeutic drug monitoring (TDM) alone cannot accurately reflect the net immune status after kidney transplantation. Within 12 months post-transplantation, we will systematically characterize dynamic trajectories of biomarkers including TTV DNA load, lymphocyte subsets and cytokines, and quantify their correlations with BK virus infection (over-immunosuppression) and acute rejection (insufficient immunosuppression). By integrating tacrolimus pharmacokinetics (PK), pharmacogenomics and immune monitoring indicators, a population pharmacokinetic-pharmacodynamic (PopPK/PD) model will be established to provide evidence supporting the paradigm shift from concentration-based dosing to immune effect-guided precision dosing.

Inclusion Criteria:

1. Aged 18-65 years, no gender restriction.
2. Patients receiving primary allogeneic kidney transplantation.
3. Maintenance immunosuppressive regimen based on tacrolimus after transplantation, with complete records of tacrolimus dosage, administration time and therapeutic drug monitoring data available.
4. Expected follow-up duration of at least 12 months at this center, and ability to complete scheduled blood and urine sample collection.
5. Subjects who fully understand the study protocol with good compliance, and provide written informed consent.

Exclusion Criteria:

1. Combined multi-organ transplantation (e.g., combined liver-kidney transplantation).
2. ABO-incompatible transplantation or patients with high preformed donor-specific antibody (DSA) titers requiring special induction regimens due to high immunological risk.
3. Patients with active HIV, HCV or HBV infection, or preoperative severe active infection requiring systematic anti-infective therapy.
4. Patients with delayed graft function or graft loss within 1 week after surgery.
5. Patients with severe hepatic or renal dysfunction.
6. Participants enrolled in other interventional clinical trials.
7. Pregnant or breastfeeding women.
8. Other conditions judged inappropriate for study participation by investigators.