The endoplasmic reticulum stress inhibitor, 4‐phenylbutyrate, attenuates chronic kidney disease induced by a model of cardiorenal syndrome (1136.12)
Bibliographic record
Abstract
Endoplasmic reticulum stress has been identified as a feature of chronic kidney disease and appears to be associated with proteinuria. We have found the endoplasmic reticulum stress inhibitor, 4‐phenylbutyrate (4‐PBA), reduced renal damage in a mouse model of acute kidney injury. Therefore, we hypothesized that inhibition of endoplasmic reticulum stress through augmenting protein folding with a low molecular weight chemical chaperone, 4‐PBA, would attenuate chronic kidney disease. Chronic kidney disease was induced in uninephrectomized wild type mice. After recovery from uninephrectomy, an angiotensin II infusion pump (1.5 ng/min/g) and a deoxycorticosterone (DOCA) pellet were subcutaneously implanted and mice were provided with 1% NaCl in the drinking water for three weeks. Blood pressure was measured and animals were placed in metabolic cages for 24 h urine collection bi‐weekly, starting one week prior to uninephrectomy. Co‐treatment with 4‐PBA (1 g/kg/day) prevented angiotensin II/DOCA/salt‐induced hypertension, cardiac hypertrophy, proteinuria, and kidney injury, as demonstrated by reduced α‐smooth muscle actin expression, protein cast formation and damaged glomeruli. However, 4‐PBA‐treated mice suffered from significantly higher mortality rates. Inhibition of cardiac hypertrophy by 4‐PBA may have been the cause of the increased mortality through congestive heart failure. Despite the higher mortality rate in 4‐PBA‐treated mice, we conclude that 4‐PBA prevents hypertension, proteinuria, cardiac hypertrophy, and chronic kidney disease in this angiotensin II/DOCA/salt model of cardiorenal syndrome. Grant Funding Source : Supported by CIHR OSO‐115895.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 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".