Long‐term protection of obese Zucker rat kidneys from fibrosis and renal failure with an angiotensin‐converting enzyme inhibitor/diuretic combination
Bibliographic record
Abstract
Some combinations of antihypertensive agents were shown to reduce proteinuria in patients with renal failure. However, preventive effects of such combinations on renal structure and function are presently unknown when treatment is administered before the onset of renal abnormalities. We thus investigated the long-term effects of an angiotensin-converting enzyme (ACE) inhibitor (perindopril)/diuretic (indapamide) combination (per/ind) in the Zucker rat, a classical model of chronic renal failure associated with obesity, hyperlipidemia, and insulin resistance. Two-month-old lean and obese Zucker rats, presenting normal renal structure and function at this young age, received per/ind (0.76 + 0.24 mg/kg of body weight/day) or the vehicle of this combination by daily gavage. After 8.5 consecutive months of treatment, those 10.5-month-old rats were used for determination of renal structural and functional parameters which were examined using standard renal clearance experiments and kidney tissue analysis. Per/ind prevented focal and segmental glomerular hyalinosis and tubulo-interstitial damage in obese rats. Treatment was also associated with a significant reduction in several staining markers of glomerular and interstitial fibrosis. The hypertrophy of superficial glomeruli and the mesangial expansion of deep glomeruli observed in control rats were reduced in per/ind-treated obese rats. The severe proteinuria observed in 10.5-month-old control obese rats was prevented by per/ind, while glomerular filtration and renal hemodynamic parameters reached similar values to those obtained in lean animals. These results show that long-term treatment with this ACE inhibitor/diuretic combination protects renal structure and function in the obese Zucker rat, emphasizing the potential efficiency of such therapy in renal failure prevention.
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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 | 0.000 |
| 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) | 0.001 | 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 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".