Comparing Whole-Blood and Plasma Tacrolimus Intra-Patient Variability for Predicting Allograft Rejection in Kidney...

Area of Science:

• Pharmacology
• Transplantation immunology
• Clinical chemistry

Background:

• Tacrolimus is crucial for preventing kidney transplant rejection.
• Intra-patient variability (IPV) in tacrolimus levels is a biomarker for outcomes.
• Plasma concentrations, not just whole-blood, may better reflect pharmacological effects.

Purpose of the Study:

• To compare the predictive performance of tacrolimus IPV from whole-blood versus imputed plasma concentrations for kidney allograft rejection.

Main Methods:

• 1302 adult kidney transplant recipients' whole-blood tacrolimus levels were used.
• Plasma concentrations were imputed using a hematocrit-binding model.
• IPV was calculated as the coefficient of variation; rejection was assessed via Kaplan-Meier and Cox models.

Main Results:

• Higher tacrolimus IPV correlated with increased rejection risk, regardless of blood or plasma matrix.
• The model using imputed plasma IPV showed no superior predictive performance (C-index) compared to the whole-blood IPV model.

Conclusions:

• Calculating IPV from hematocrit-imputed plasma tacrolimus concentrations offers no significant predictive advantage over the standard whole-blood method for predicting kidney allograft rejection.
• Further research is needed to determine if IPV from direct plasma measurements or advanced models can outperform whole-blood IPV.