Hypertension induces proteinuria and renal fibrosis associated with endoplasmic reticulum (ER) stress in the Dahl salt sensitive rat
Bibliographic record
Abstract
Hypertension and proteinuria are associated with the progression of chronic kidney disease (CKD). CKD occurs via a process of kidney fibrosis and nephron loss. The Dahl salt sensitive hypertensive rat (Dahl SS) is a model of hypertension caused by high salt, resulting in proteinuria and CKD. We hypothesized that hypertension‐induced proteinuria in the Dahl SS leads to renal fibrosis through the initiation of ER stress and the unfolded protein response (UPR). The UPR is an important modulator in the differentiation of various cell types, including myofibroblasts. We tested this using two models of hypertension, the Dahl SS rat and the spontaneously hypertensive rat (SHR) treated with a high salt (8% NaCl) or maintained on a low salt (0.4% NaCl) diet for 14 days. Kidneys from these animals were processed for histology and immunohistochemistry for markers of both ER stress and fibrosis. In the high salt treated Dahl SS rat, intratubular protein casts were observed. These rats also displayed renal fibrosis as shown by trichrome and α‐smooth‐muscle actin staining, and ER stress, shown by GRP78 and CHOP staining. Contrarily, the SHR developed no significant proteinuria or interstitial fibrosis in response to high salt despite malignant hypertension. These results suggest that hypertension‐induced proteinuria is associated with an ER stress response and renal interstitial fibrosis. 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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| 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".