Impact of transiting from fluorescent polarisation immunoassay to high-performance liquid chromatography–tandem mass spectrometry for immunosuppressant levels analysis in kidney transplant patients

Abstract

Background: High-performance liquid chromatography–tandem mass spectrometry (HPLC-TMS) is preferred to fluorescent polarisation immunoassay (FPIA) in therapeutic drug monitoring (TDM), as it only measures active drug. Our hospital replaced FPIA with HPLC-TMS for analysis of calcineurin inhibitor (CNI) levels. Preliminary studies demonstrated significantly lower CNI levels with HPLC-TMS versus FPIA in kidney transplant recipients (KTRs). Most studies evaluating CNI exposure in KTRs used FPIA, posing challenges in interpreting HPLC-TMS levels. This study aimed to compare the effectiveness and safety outcomes in the one-year period before (FPIA period) and after (HPLC-TMS period) the switch. Methods: A retrospective cohort study was conducted on KTRs receiving ciclosporin (CsA) or tacrolimus (FK). Primary effectiveness end points were biopsy-proven acute rejection (BPAR) rate and estimated glomerular filtration rate (eGFR); safety end points were viral infections and hospitalisation for infection. The secondary end point was change in CNI levels during the FPIA versus HPLC-TMS periods. Results: A total of 307 patients were analysed (CsA n=182, FK n=125). BPAR only occurred in two patients in the HPLC-TMS period among the CsA cohort ( p=0.50), but it occurred in six patients in the FPIA period and one patient in the HPLC-TMS period ( p=0.13) among the FK cohort. Median eGFR were similar in both periods (CsA: 52.2 mL/min/1.73 m2 (interquartile range (IQR) 39.8–67.6) vs. 52.5 mL/min/1.73 m2 (IQR 37.1–68.0), p=0.65; FK: 57.7 mL/min/1.73 m2 (IQR 39.1–80.0) vs. 56.4 mL/min/1.73 m2 (IQR 33.5–76.7), p=0.08). There were no significant differences in safety outcomes. The median change in CNI levels from the FPIA period to the HPLC-TMS period was –20.5% (IQR –32.5 to –3.9) and –6.9% (IQR –17.7 to 8.0) among CsA and FK cohorts, respectively ( p<0.01). Conclusion: The switch from FPIA to HPLC-TMS for CNI TDM in KTRs did not yield significant changes in clinical end points.