Discussion
tremor, tremor-related impairments, medication-induced tremor, tremor-related impairment, diabetes
PATHOPHYSIOLOGY, DIABETES
This study shows that mild or severe tremor frequently impairs daily life activities of SOTR. Tacrolimus trough concentration was a main determinant of tremor. Importantly, mild and severe tremor-related impairments were strongly associated with lower HRQoL, independent of other known determinants of tremor.Our results confirm that SOTR frequently experience tremor-related impairment of ADL. A previous study reported similar tremor prevalence compared to our study (The notion that tacrolimus trough concentrations are independently associated with tremor-related impairment among SOTR is important for treating physicians to consider during treatment regimens. Furthermore, this notion highlights the need for alternative immunosuppressive treatment regimens that are less likely to cause tremor, while maintaining low risks of rejection. Since dose-dependency seems to be key in the pathophysiology of medication-induced tremor, extended-release preparations may be able to reduce tremor prevalence by reducing peak-to-trough variability (The potential impact of tremor on the lives of SOTR is further highlighted by the associations of severe tremor with both lower mental and physical HRQoL. These results are generally in line with findings in previous smaller studies. For example, Langone et al. reported an improved quality of life after a reduction in tremor severity, in a small cohort of 38 kidney transplant recipients (A major strength of this study is the large number of included SOTR with available data regarding subjective tremor and HRQoL. Additionally, we included kidney, liver, lung, heart, and small intestine transplant recipients, allowing for evaluation of tremor prevalence among these patient groups. In addition, the cohort was well-characterized, allowing us to adjust for many potential confounders, including extensive clinical data, laboratory measurements, and treatment regimens. A limitation of the current study is that the participants mainly used tacrolimus-based treatment regimens, and associations of cyclosporine and other immunosuppressive drugs with tremor could therefore be incompletely studied. In addition, since patients were not evaluated before transplantation, the presence and exacerbation of preconditions which may cause tremor could not be assessed. Non-CNI users with tremor more frequently had diabetes compared to those without diabetes, which may partly explain the high prevalence of tremor in this subgroup. Nevertheless, this observation cannot fully explain the tremor occurrence in this subgroup, and future studies are needed to gain insights into the tremor susceptibility of some SOTR without CNI-use. Lastly, due to the observational design of the study, we cannot draw conclusions regarding causality of our findings. Moreover, the current cross-sectional study cannot identify trajectories of tremor before and after transplantation, and therefore longitudinal studies assessing the determinants of tremor are warranted. Such studies may also help to account for potential tacrolimus dosage adaptations that clinicians may conduct in patients with severe tremor.SOTR frequently report tremor-related impairment of ADL. Tacrolimus trough concentrations appeared a main determinant of tremor among SOTR. The strong and independent association of tremor-related impairment with lower HRQoL warrants further studies into the effects of tacrolimus on tremor.