Tacrolimus-Associated Tremor in Renal Transplant Patients: Potential Impact of the Galenic Formulation.

Abstract

Background/Objectives: Tacrolimus is the most used immunosuppressive agent in solid organ transplantation due to its efficacy in preventing acute rejection, but it has a narrow therapeutic range, and overexposure often leads to toxicities, including neurological side effects like tremors. Tremor affects up to 54% of renal transplant patients under tacrolimus. Extended-release tacrolimus (LCPT) has demonstrated efficacy in reducing tremor severity, as evidenced by studies employing quality of life (QoL) questionnaires, the Fahn-Tolosa-Marin (FTM) scale, and Accelerometer devices. The objectives of this study were to evaluate the benefits of the conversion to LCPT formulation in kidney transplant recipients experiencing tremors on prolonged-release tacrolimus (PR-TAC) treatment and to validate the DyCare device, a wearable wireless sensor for tremors. Results: The DyCare device measured tremor frequencies of 8.74 ± 0.11 Hz and 1.36 ± 0.08° and 17.38 ± 1.16°, as root mean square (RMSx100 for accelerometer and Gyroscope, respectively) in PR-TAC patients. After switching ten patients to LCPT, tremor severity significantly decreased, as confirmed by DyCare and the QoL in the Essential Tremor Questionnaire (QUEST). Additionally, LCPT allowed a 34% reduction in tacrolimus dosage while maintaining therapeutic trough concentrations. Immunological and pharmacodynamic biomarkers (p-miR-210-3p, p-IL10, p-IL12p70, p-IFNγ uCXCL10, NFAT-regulated gene expression) confirmed stable immunosuppression post-conversion. Conclusions: The conversion to the LCPT formulation significantly reduced tremors in kidney transplant recipients without altering their immunological status, as confirmed through a panel of immunologic and pharmacodynamic biomarkers. The DyCare device enables a precise quantification of tremors in transplant recipients, allowing physicians to optimize treatment strategies.