Clinician Beware: Tacrolimus Immunoassay vs. Mass Spectrometry

Purpose Tacrolimus is one of the most frequently prescribed immunosuppressants in lung transplantation. However, many clinicians are not aware that there are different types of assays to measure tacrolimus concentrations. Two assays used are the antibody-based immunoassay and mass spectrometry. At our institution, we employ an immunoassay. Since the use of antibodies is the basis for this technology, there is the potential for cross-reactivity. Unfortunately, one patient continued to have elevated tacrolimus levels even when no drug was given for a week and when a mass spectrometry test was ordered, this showed undetectable drug concentrations. This had dire consequences for the patient and was the impetus for us to compare the difference in drug concentrations based on our immunoassay and mass spectrometry technologies at our institution. Methods We tested 221 unique tacrolimus drug samples using Siemens EXL and RXL immunoassay and mass spectrometry. The mean and standard deviations were calculated for each assay with a 95% confidence interval as well as the mean difference between the two assays. Results The mean tacrolimus concentrations (ng/mL) using the immunoassay and mass spectrometry was 11.01±5.35 (CI, 95% 0.70) and 9.29±5.04 (CI, 95% 0.66), respectively. The mean difference between the two assays was 2.04. As a percentage, the two assays were >3 ng/mL apart 20% of the time. 3% of cases had levels that were >8 ng/mL apart. Conclusion Clinicians need to be aware that there are two types of assays available to test tacrolimus concentrations. At times, these assays can produce very discordant results that can have important clinical consequences. While in our experience there was no common thread that would predict when significant discordant results would appear, some clues may include very low tacrolimus doses to achieve therapeutic drug levels, unexplained allograft dysfunction, persistently elevated drug levels even when holding multiple doses, and exaggerated responses when initially starting tacrolimus post-operatively.