Hypertensive Diabetic Kidney Disease Increases the Severity of Experimental AKI
Bibliographic record
Abstract
Background: Patients with diabetic kidney disease (DKD) are at increased risk of severe AKI and adverse outcomes. Since DKD may alter cellular and therapeutic responses in AKI, there is a need to establish a model to evaluate the mechanisms and therapeutics of AKI in the context of DKD. These studies address this deficiency by characterizing AKI in transgenic mice with renin-induced hypertension and progressive DKD. Methods: Hypertensive male transgenic TThRen (TR+) mice, which over-express renin in the liver, were treated +/- streptozotocin to induce diabetes (DM). Tail cuff BP; urinary albumin/creatine ratio (ACR); BUN; and transdermal GFR (tGFR) were measured from 11-31 wks in DM and non-diabetic (ND) cohorts. After optimizing renal pedicle clamp times in DM (19 mins) vs. ND mice (24 mins) to induce similar injury after ischemia-reperfusion AKI (IR-AKI), mice underwent bilateral IR-AKI at 32 wks, followed by serial BP, BUN, ACR and tGFR measurements over 8 wks. Results: ND and DM TR+ mice had increased albuminuria (31wk ACR, mg/mg: ND TR - vs. +, 17.7 (2.0) vs. 498.2 (325.2), p<0.0001; DM TR - vs. +, 136.7 (50.3) vs. 1028 (420.3) p<0.01), with no significant difference between DM and ND TR+ mice. BP was elevated in TR+ mice, with no difference between DM and ND mice, but there was a decrease in tGFR in DM TR+ vs. ND TR+ over time (2 way ANOVA, p<0.05). After IR-AKI, DM TR+ mice had more severe injury than DM TR- mice (e.g.: day1 BUN, mg/dl: DM TR- vs. +, 56.7 (8.6) vs. 95.1 (11.8), p<0.01), but there was no difference in severity of injury in ND TR- and + mice. This was associated with a progressive increase in albuminuria, but after 14 days, no difference in tGFR in DM TR- vs. + mice, and no change in albuminuria or tGFR in ND TR- vs. + mice up to 8 weeks after IR-AKI. Conclusions: Hypertensive DM and ND mice develop albuminuria, but only hypertensive DM mice develop reduced tGFR consistent with progressive DKD. After optimizing renal pedicle clamp times to induce similar injury, only hypertensive DM mice had increased injury and progressive nephropathy after IR-AKI, as determined by increased albuminuria, compared with non-hypertensive DM and both hypertensive and non-hypertensive ND controls. This model mimics human disease as there is increased injury and progressive DKD after IR-AKI mice with pre-existing DKD. Funding: Other U.S. Government Support
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".