Effect of Prolonged-Release vs. Immediate-Release Tacrolimus on Neurocognition in Kidney Transplant Recipients: A Pilot Randomized Controlled Trial (RCT)
Bibliographic record
Abstract
Background: Tacrolimus is known to cause neurological side effects and elderly individuals seem particularly vulnerable. It is unknown if the prolonged-release (PR) tacrolimus (Envarsus XR) formulation minimizes neurocognitive side effects compared to immediate release (IR) tacrolimus due to lower peak serum levels. We aimed to compare the neurocognitive side effects of PR and IR tacrolimus in elderly kidney transplant recipients within the first months post-transplantation. Methods: In this single center, prospective, open-label, randomized trial, 64 kidney transplant recipients aged 60 or above were randomized to PR tacrolimus or IR tacrolimus between 4 and 8 weeks post-transplantation and followed for 6 weeks. Neurocognitive performance was assessed by the Montreal Cognitive Assessment (MOCA) and Digit Symbol Substitution Test (DSST). Secondary outcomes of tremor and quality of life were assessed through the Quality of Life in Essential Tremor Questionnaire (QUEST) and Organ Transplant Symptom and Wellbeing Instrument (OTSWI). Results: 32 patients were randomized to the IR tacrolimus arm and 31 into the PR tacrolimus arm. Mean age was 69 in both arms and 37% were women. Table 1 shows the assessment scores for the primary and secondary outcomes. There was no statistically significant difference between groups in the change in MOCA or DSST scores from baseline to 6 weeks or in tremor or quality of life measures. Table 1. - Neurocognitive Testing and Tremor Results.P-values were computed from ANCOVA adjusting baseline value and without adjusting for multiplicity. Values shown are mean and (standard deviation). IR Tacrolimus (n=32) ER Tacrolimus (n= 31) p Primary Outcomes Baseline MOCA score 23 (3.8) 22 (5.3) Baseline corrected MOCA score 23.3 (3.7) 22 (7) 6-week MOCA score 22.8 (7) 22 (6.3) 6-week corrected MOCA score 24.7 (3.6) 23 (5) MOCA (corrected) score difference 1.2 (2.1) 0.2 (2.9) 0.06 Baseline DSST score 35.1 (13) 32.5 (14) 6-week DSST score 35.7 (11.5) 34.3 (16) DSST score difference 1.0 (7.8) 1.26 (7.5) 0.96 Secondary Outcomes Baseline Quest Summary Score 8.2 (14.4) 7.7 (12.3) 6-week Quest Summary Score 7.4 (11.4) 4.3 (5.8) Quest Summary Score difference -1.0 (10.4) -2.9 (10.0) 0.15 Baseline OTSWI 25.5 (18.3) 25 (18) 6 Week OTSWI 23.5 (19.2) 19 (13) OTSWI Score difference -2.1 (9.7) -6.2 (12.0) 0.1 Conclusions: Although prior studies indicated improvement in neurological side effects in PR tacrolimus compared with IR tacrolimus, the improvement does not appear to extend to neurocognitive side effects as assessed by the MOCA or DSST tests in this cohort. Funding: Commercial Support - Veloxis Pharmaceuticals, Inc
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".