The association between tacrolimus exposure and tremor, headache and insomnia in adult kidney transplant recipients: A systematic review
Bibliographic record
Abstract
PURPOSE: Tremor, headache and insomnia have been linked to the immunosuppressant, tacrolimus. The aim of this systematic review was to determine if there is a correlation between tacrolimus exposure and new-onset tremor, headache and insomnia experienced by adult kidney transplant recipients. METHODS: PubMed, Embase, Cochrane Library and CINAHL databases were searched up to 11 April 2023 for published studies which reported on tacrolimus exposure in adult kidney transplant recipients, alongside information on treatment-emergent neurologic manifestations, including tremor, headache and insomnia. Review articles, case studies, conference abstracts and articles not published in English in peer-reviewed journals were excluded. The Physiotherapy Evidence Database and Newcastle-Ottawa Quality Assessment Scales were used to assess risk of bias. Extracted data was analysed via a narrative synthesis. RESULTS: Eighteen studies involving 4030 patients in total were included in the final analysis. These comprised five randomised control trials and thirteen observational studies. Studies failed to find significant association between tacrolimus trough concentrations in whole blood and the incidence of neurologic side effects such as tremor, headache and insomnia; however, in one study the incidence of toxicity requiring a dose reduction increased with increasing, supratherapeutic targeted levels. Females, especially Black females, and older age were positively associated with the prevalence of neurologic adverse effects. Results were conflicting regarding whether extended-release formulations were associated with fewer neurologic complications than immediate-release formulations. CONCLUSION: The varied study designs and criteria for reporting tremor, headache and insomnia impacted on the quality of the data for exploring the relationship between tacrolimus exposure and the onset of neurologic manifestations experienced after kidney transplantation. Studies that examine defined neurologic complications as the primary outcome, and that consider novel markers of tacrolimus exposure while assessing the potential contribution of multiple covariate factors, are required.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.027 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.008 |
| Bibliometrics | 0.008 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".