Unveiling Kidney Disease Progression in Autosomal Recessive Polycystic Kidney Disease with Hypertension: Insights from the SS-PCK Rat Model
Bibliographic record
Abstract
Background: The SS-PCK rat model offers a novel approach to investigate autosomal recessive polycystic kidney disease (ARPKD) complicated by salt-sensitive hypertension. This model integrates the mutated human orthologous Pkhd1 allele from PCK rats into a Dahl salt-sensitive (SS) background, providing a unique platform to explore the influence of salt sensitivity on cyst formation and renal pathology. Intriguingly, male SS-PCK rats demonstrated significantly elevated blood pressure and renal pathology even under normal salt conditions, presenting distinct medullary cyst formation and reduced renal cyst size compared to PCK rats. Histological examination revealed small cysts in both cortical and medullary regions of SS-PCK kidneys, with renal function parameters declining progressively with age. We examined cellular mechanisms and the effects of an ACE inhibitor. Methods: PCK and SD rats were obtained from The Jackson Laboratories Japan, Inc, and SS and SS-PCK rats were from Medical College of Wisconsin. Males were given standard chow with a normal salt level. Furthermore, Enalapril was administrated in SS-PCK rats from 5 to 16 weeks of age. Kidney samples were prepared for analytical studies. Results: Expression analyses indicated decreased levels of Cytochrome P450 4 (Cyp4) family genes, including Cyp4a3 and Cyp4a8, in SS-PCK rats compared to PCK rats, while epithelial sodium channel (ENaC) expressions, specifically β-ENaC and γ-ENaC, were significantly elevated. Additionally, Aquaporin-2 (AQP2) expression was notably higher in SS-PCK rats. Enalapril treatment in SS-PCK rats improved renal function, evidenced by significantly lower serum urea nitrogen and creatinine levels, along with increased Cyp4a1 expression. Furthermore, Enalapril treatment reduced β-ENaC and γ-ENaC expressions, without affecting AQP2 expression. Conclusion: These findings elucidate the complex mechanisms underlying ARPKD progression, emphasizing the involvement of the Cyp4 signaling pathway and Angiotensin II-induced ENaC expression. Enalapril treatment effectively mitigated hypertension and renal complications, highlighting the therapeutic potential of ACE inhibitors in managing ARPKD and hypertension-associated renal disease. 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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 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".