Transplant patient classification and tacrolimus assays: more evidence of the need for assay standardization.

Background: A global tacrolimus proficiency study recently showed clinically significant variability between laboratories, the inability of a common calibrator to harmonize methods, and differences in patient classification depending on the test method. The authors evaluated (1) the effect of a change in methodology on patient classification based on tacrolimus blood concentration and (2) the ability of 2 methods to position the concentration in a given specimen within the correct range.

Methods: A total of 839 consecutive samples were analyzed at The Rogosin Institute and New York Presbyterian Hospital for routine tacrolimus monitoring over 30 days. Concordance analysis between the methods was performed covering dosage target ranges of 8-10, 6-8, 4-6 ng/mL currently used at our center. Six Sigma Metrics were applied to statistically evaluate the discordance rate.

Results: Deming regression comparing liquid chromatography-tandem mass spectrometry and immunoassay yielded y = 0.927x - 0.24; 95% confidence interval, 0.903-0.951; R = 0.875; n = 839. There were 310 pairs (37%) discordant by 1, 21 (2.5%) discordant by 2, and 4 (0.5%) discordant by 3 therapeutic ranges. Surprisingly, 40% of patient samples were discordant when therapeutic ranges were 2 ng/mL wide. This discordant rate is equivalent to 1.7 Sigma and falls far below the minimum acceptable threshold of 3 Sigma.

Conclusions: Both methods are capable of measuring tacrolimus in the clinically relevant range between 1 and 10 ng/mL, yet 40% of the samples were discordant with an unacceptable Sigma level. Standardization of tacrolimus assays will mitigate this issue.