Usefulness of mycophenolic acid monitoring with PETINIA for prediction of adverse events in kidney transplant recipients

Abstract

Background Therapeutic drug monitoring of mycophenolic acid (MPA) is required to optimize the immunosuppressive effect and minimize toxicity. We validated a new particle-enhanced turbidimetric inhibition immunoassay (PETINIA) for the determination of MPA levels and evaluated the relationship of MPA trough level with drug-related adverse events. Methods PETENIA and liquid chromatography-mass spectrometry (LC-MS) were used to determine MPA concentrations from 54 kidney transplant recipients (KTRs). Agreement between PETINIA and LC-MS results was assessed by Passing-Bablok regression and the Bland-Altman plot method. The association of adverse events with MPA trough level obtained by PETINIA was analyzed. Results PETINIA revealed a good agreement with the LC-MS; Regression analysis gave an equation of y = 1.27x − 0.12 (r² = 0.975, p < 0.001). PETINIA showed a systemic positive bias with a mean difference of 0.66 mg/L compared to LC-MS. However, the magnitude of the positive bias decreased to 0.44 mg/L within the therapeutic range of MPA. Multiple logistic regression showed that MPA trough level determined by PETINIA was an independent risk factor for adverse events (odds ratio 2.28, 95% CI 1.25–4.16, p = 0.007). MPA trough level predicted adverse events with a sensitivity of 77.8% and a specificity of 86.7% using a cut-off level of 5.25 mg/L. Conclusions Good correlation between the two methods indicates that PETINIA is an acceptable method for the monitoring of MPA therapeutic levels. Furthermore, MPA trough level obtained by PETINIA is a useful monitoring tool to minimize toxicity in KTRs.

Key Words:

• Adverse event
• kidney transplantation
• LC-MS
• mycophenolate
• PETINIA
• validation

Acknowledgements

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &Welfare, Republic of Korea (HI15C0001 and HI13C1232).

Authorship

JYH wrote the initial manuscript; HYJ, JYC, SHP, and YLK performed the research; HKK, SH, and CDK assisted in writing the discussion; DIW and KES analyzed data and edited the manuscript; JHC designed the paper and revised the manuscript.

Disclosure statement

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.