Challenged comparison of tacrolimus assays

Area of Science:

• Pharmacology
• Clinical Chemistry
• Transplant Medicine

Background:

• Tacrolimus trough concentrations are vital for immunosuppression in solid organ transplant recipients.
• Existing immunoassays may overestimate tacrolimus levels due to metabolite cross-reactivity, especially in high-dose patients.

Purpose of the Study:

• To investigate the correlation between different tacrolimus assays (immunoassays and mass spectrometry) in patients with normal and high tacrolimus dose requirements.
• To identify potential biases and differences in tacrolimus measurements across various assay methods.

Main Methods:

• Compared four tacrolimus assays: two immunoassays (CMIA, ECLIA) and two LCMS assays.
• Analyzed routine blood samples from 37 control and 72 high-dose patients.
• Utilized Deming regression, Pearson correlation, Bland-Altman plots, and bias calculation.

Main Results:

• CMIA showed a 23-26% positive bias compared to LCMS; ECLIA showed an 11-13% positive bias.
• Correlations were good in control groups but weaker in high-dose groups (CMIA vs. LCMS: r=0.91; ECLIA vs. LCMS: r=0.93).
• LCMS assays demonstrated excellent correlation (r>0.99) with no bias between them.

Conclusions:

• While tacrolimus assays generally correlate well, significant inter-assay differences exist.
• These differences are more pronounced in high-dose tacrolimus recipients, potentially impacting therapeutic drug monitoring.
• Mass spectrometry assays offer superior accuracy and consistency compared to immunoassays.