Assessing the Influence of Sex on the CD1 Nephrectomized Streptozoto-cin-Induced Diabetic Kidney Disease Model
Bibliographic record
Abstract
Background: Diabetic kidney disease (DKD) is the leading cause of kidney failure in North America. DKD is characterized by a progressive increase in albuminuria, glomerular hypertrophy, expansion of the glomerular mesangium, thickening of the glomerular basement membrane, and tubulointerstitial fibrosis and atrophy. Recent studies have shown that sex and sex hormones are important factors to consider in the development and progression of DKD. Presently, the hallmarks of this disease have primarily been studied in male rodent models. Here we explored the influence of sex in the CD1 nephrectomized streptozotocin (STZ)-induced murine model. Methods: To induce DKD, 8-week-old CD1 mice underwent a right nephrectomy. After 1 week of recovery, they were injected IP with 200mg/kg STZ and followed for 12 weeks. Outcomes included urinary albumin-to-creatinine ratio (ACR), blood pressure (BP), weight, kidney and glomerular hypertrophy and kidney pathology. Results: STZ dose required reduction in females to 150mg/kg due to high initial mortality. However, females often required reinjection after 2 weeks at 100mg/kg to induce hyperglycemia. Males had a greater decrease in endpoint weight and increase in BP. Both sexes developed comparable hyperglycemia, kidney hypertrophy and albuminuria, although ACR was more variable in females. Glomerular hypertrophy was more pronounced in male diabetics, as was basement membrane thickening. Serum TGFβ1 levels were increased only in females, which may be related to their known greater TGFβ1 production after puberty compared to male mice. However, urine TGFβ1 increased comparably in both sexes. Accumulation of profibrotic proteins fibronectin and collagens I, III, IV, and markers of T-cell and macrophage infiltration were also similar between sexes. Conclusions: Female mice required a modification of the STZ protocol to maintain survival, but induce hyperglycemia. While somewhat more pronounced in male mice, both sexes developed typical characteristics of DKD. Future studies evaluating the potential of therapeutic interventions can thus be assessed in both sexes in this model of DKD. Funding: Government Support - Non-U.S.
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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) | 0.002 | 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".