Dapagliflozin vs. Ramipril Therapy in Mice with Alport Syndrome
Bibliographic record
Abstract
Background: Angiotensin-converting enzyme inhibitors (ACEi) have been the best studied treatment for Alport syndrome with established benefits for renal function and survival in animals and humans. Recent clinical trials have shown that sodium glucose cotransporter 2 inhibitors (SGLT2i) are a key disease-modifying therapy to prevent the progression of chronic kidney disease when used on a background of renin-angiotensin-aldosterone system (RAAS) blockade. The objective of this study is to investigate whether SGLT2i exerts renoprotection as much as ACEi in Alport syndrome. Methods: We studied male Col4α3 knockout mice, an Alport syndrome model, on a 129S1/SvImJ background. Dapagliflozin (1.5 mg/kg/day) or Ramipril (10 mg/kg/day) were orally administered via drinking water, starting at 4 weeks of age to 10 weeks of age (N=6-8/group). Wild-type (WT) and Alport littermates received vehicle for the same duration and served as controls. Glomerular filtration rate (GFR) was measured by inulin-FITC clearance in conscious mice, and kidneys were processed for histology (PAS, Sirius Red staining). Results: Alport mice treated with Dapagliflozin had enhanced glucose excretion in urine, but blood glucose level was not changed. At 10 weeks of age, Alport mice developed a significant weight loss, decreased GFR/body weight, and elevated BUN. These were attenuated by Ramipril, but not by Dapagliflozin. Histological analysis of Alport mouse kidneys showed global and segmental glomerulosclerosis, tubular casts and tubulointerstitial fibrosis, which were more consistently improved by Ramipril than by Dapagliflozin. Conclusions: Ramipril had more favorable effects on preservation of renal function and renal architecture in Col43 knockout Alport mice than Dapagliflozin. Our head-to-head comparison indicates that SGLT2i may not be an alternative option for ACEi in glomerular diseases. Further studies are currently ongoing to investigate the effects of a higher dose of Dapagliflozin and of combined treatment of SGLT2i with RAASi. Funding: Private Foundation Support
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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 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".