title: 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 (r(2) = 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.
authors.affiliation: a Department of Clinical Pathology , Kyungpook National University School of Medicine , Daegu , Korea ;
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Ham
authors.affiliation: b Department of Internal Medicine , Kyungpook National University Hospital , Daegu , Korea ;
authors.forename: Hee-Yeon
authors.initials: HY
authors.lastname: Jung
authors.affiliation: b Department of Internal Medicine , Kyungpook National University Hospital , Daegu , Korea ;
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: b Department of Internal Medicine , Kyungpook National University Hospital , Daegu , Korea ;
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Park
authors.affiliation: b Department of Internal Medicine , Kyungpook National University Hospital , Daegu , Korea ;
authors.forename: Yong-Lim
authors.initials: YL
authors.lastname: Kim
authors.affiliation: c Department of Surgery , Kyungpook National University School of Medicine , Daegu , Korea.
authors.forename: Hyung-Kee
authors.initials: HK
authors.lastname: Kim
authors.affiliation: c Department of Surgery , Kyungpook National University School of Medicine , Daegu , Korea.
authors.forename: Seung
authors.initials: S
authors.lastname: Huh
authors.affiliation: b Department of Internal Medicine , Kyungpook National University Hospital , Daegu , Korea ;
authors.forename: Chan-Duck
authors.initials: CD
authors.lastname: Kim
authors.affiliation: a Department of Clinical Pathology , Kyungpook National University School of Medicine , Daegu , Korea ;
authors.forename: Dong Il
authors.initials: DI
authors.lastname: Won
authors.affiliation: a Department of Clinical Pathology , Kyungpook National University School of Medicine , Daegu , Korea ;
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Song
authors.affiliation: b Department of Internal Medicine , Kyungpook National University Hospital , Daegu , Korea ;
authors.forename: Jang-Hee
authors.initials: JH
authors.lastname: Cho
mesh_terms: D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D007118:Immunoassay; D007159:Immunologic Tests; D007166:Immunosuppressive Agents / Q000032:analysis / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D009173:Mycophenolic Acid / Q000032:analysis / Q000627:therapeutic use*; D011446:Prospective Studies; D012044:Regression Analysis; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid
keywords: Adverse event; LC-MS; PETINIA; kidney transplantation; mycophenolate; validation