P2.03 RECOMBINANT HUMAN ERYTHROPOIETIN ALTERS SUBCUTANEOUS RESISTANCE ARTERY ENDOTHELIAL FUNCTION THROUGH A MECHANISM INVOLVING OXIDATIVE STRESS AND ENDOTHELIN-1 IN PATIENTS WITH STAGE 4 CHRONIC KIDNEY DISEASE
Bibliographic record
Abstract
Recent studies have raised concern about the safety of recombinant human erythropoietin (RhuEPO) because of evidence of an increase in the risk of cardiovascular disease in chronic kidney disease (CKD) patients. In the present study we investigated the effect of RhuEPO on the function of resistance arteries isolated from CKD patients. 19 patients (mean age 63 ± 14 years) with stage 4 CKD (mean eGFR 20 ± 5 mL/min/1.73m 2 ), none treated with RhuEPO, were included. Resistance arteries from gluteal subcutaneous tissue were assessed on a pressurized myograph. Endothelium-dependent and independent relaxations were tested with acetylcholine and sodium nitroprusside respectively, with RhuEPO (0, 1, 10 and 20 UI/mL). Tempol (10 −3 M), a superoxide dismutase mimetic, was used to inhibit oxidative stress. ABT-627 (10 −7 M) was used as a selective endothelin subtype A receptor antagonist. At 20 UI/mL, RhuEPO had no effect on norepinephrine-induced vasoconstriction (n = 10) nor on sodium nitroprusside-induced relaxation (n = 10). RhuEPO altered endothelium-dependent relaxation in a dose-dependent manner (maximal relaxation with RhuEPO at 0, 1, 10, 20 UI/ mL, 77.7 ± 3.5 %, 68.5 ± 4.7%, 53.2 ± 3.8 %, 45.7 ± 4.6 %, P<0.001, n = 7–14). Tempol and ABT-627 partially reversed the altered endothelial function in presence of RhuEPO 20 UI/mL (P<0.01, P<0.01, respectively). Conclusion: RhuEPO alters endothelial function of subcutaneous resistance arteries in predialysis CKD patients via a mechanism in part involving oxidative stress and signaling through endothelin subtype A receptors, which could contribute to the deleterious effect of RhuEPO described in large interventional trials.
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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 | 0.001 | 0.000 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".