Elevated tacrolimus exposure variability predicts transplant renal insufficiency

Area of Science:

• Nephrology
• Immunosuppression
• Transplantation

Background:

• Optimizing immunosuppression is key for long-term graft survival in renal transplantation.
• Tacrolimus (TAC) is a vital immunosuppressant, but under- or over-exposure can lead to rejection or renal injury.
• This study investigates TAC exposure's impact on graft function to identify high-risk post-transplant patients.

Purpose of the Study:

• To assess the impact of Tacrolimus (TAC) exposure on graft renal function.
• To identify high-risk individuals for post-transplantation complications.
• To correlate TAC exposure parameters with renal insufficiency post-transplant.

Main Methods:

• Retrospective cohort study of adult kidney transplant recipients (2019-2023).
• Cox regression analysis to evaluate risk effects of TAC exposure parameters (mean, median, STD, CV).
• Kaplan-Meier method for survival analysis of stabilized graft renal function.

Main Results:

• Graft renal insufficiency occurred in 19.22% of recipients.
• A TAC target trough concentration standard deviation (STD) ≥5 showed a 4.55-fold increased risk (p=0.004).
• Higher TAC coefficient of variation (CV) and lower time in therapeutic range (TTR <0.3) were associated with increased graft renal insufficiency risk.

Conclusions:

• Elevated TAC trough concentrations, higher CV, and lower TTR significantly increase transplant renal insufficiency risk.
• Identifying high-risk recipients and optimizing TAC levels are crucial for better outcomes.
• Interventions to maintain TAC within recommended ranges can improve renal transplant recipient survival.