Increased Blood-Brain Barrier Permeability and Cognitive Impairment in Patients With ESKD
Why this work is in the frame
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Bibliographic record
Abstract
IntroductionChronic kidney disease (CKD) is associated with an increased risk of cognitive impairment. This cognitive impairment is associated with an increased permeability of blood-brain barrier (BBB) in rodents with CKD, linked to activation of aryl hydrocarbon receptor (AhR) by indoxyl sulphate (IS). The objective of the BREIN study was to confirm the increased BBB permeability in humans with CKD.MethodThe BREIN comparative study (NCT04328415) prospectively included patients with end-stage kidney disease (ESKD) and controls healthy volunteers matched in age, sex, and level of education to a patient. In all participants, BBB permeability was quantified by brain 99mTc-DTPA SPECT/CT as a percentage of injected activity (% IA). A battery of neurocognitive tests was performed, and serum uremic toxins accumulation and AhR activation were assessed.ResultsFifteen patients with ESKD and 14 healthy volunteers were analyzed. Patients with ESKD had higher BBB permeability compared to controls: 0.29 ± 0.07 versus 0.14 ± 0.06 %IA, P = 0.002. Patients with ESKD displayed lower Montreal Cognitive Assessment test (MoCA) score: 22.0 ± 5.0 versus 27.3 ± 2.8, P = 0.008; impaired short-term memory (doors test): 12.5 ± 3.4 versus 16.5 ± 3.4, P = 0.005; higher Beck depression score 8.1 ± 9.1 versus 2.7 ± 3.4, P = 0.046; and slightly more daily cognitive complaints: 42.5 ± 29.3 versus 29.8 ± 14.0 P = 0.060. Patients with ESKD displayed higher IS levels (86.1 ± 48.4 vs. 3.2 ± 1.7 μmol/l, P = 0.001) and AhR activating potential (37.7 ± 17.8% vs. 24.7 ± 10.4%, P = 0.027). BBB permeability was inversely correlated with MoCA score (r = −0.60, 95% confidence interval [−0.772 to −0.339], P = 0.001) in the overall population.ConclusionPatients with ESKD display an increased BBB permeability compared to matched healthy volunteers. Association with uremic toxins and cognitive impairment needs to be assessed in larger cohorts of patients.
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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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 it