Xanthine Oxidase in Rats, Mice, and Humans with Polycystic Kidney Disease
Bibliographic record
Abstract
Background: Raising uric acid (UA) worsens PKD in rodents (Edelstein, AJP, 2024). Xanthine oxidase (XO) results in the formation of uric acid and generates reactive oxygen species like H2O2. There is increasing evidence that increased XO in addition to UA plays role in disease. Methods: To gain insight into whether increased XO is associated with cyst growth, XO activity was measured in PCK rats, Pkd1RC/RC (RC) mice and 34 patients at HALT-PKD study 24 month visit. XO in rodents (iU/ug): Fluorometric assay kit that detects H2O2. XO in humans (ng/mL): ELISA that directly measures XO. Fast progressors (N=17) defined as increase in height corrected total kidney volume (TKV) of >7%/yr. Fast and slow progressors were matched for clinical characteristics including age, gender, Pkd1 mutation. Values=means Results: Kidney XO was higher in PCK rats vs. RC mice (19 vs. 6, P<0.05). PCK rats: XO was lower in serum (119 vs 145, P<0.01), kidney (19 vs 34, P<0.05) and liver (1505 vs 2173, P<0.01) vs wildtype. Higher cyst index correlated with lower serum (R2 0.66, P=0.09) and kidney (R2=0.47, P=0.02) XO. RC mice: No correlation between cyst index and serum XO (R2=0.06, p=NS) or kidney XO (R2=0.06, NS). Oxypurinol decreased cyst growth (Edelstein et al. AJP, 2024) and decreased both serum UA and serum XO (91 vs. 171, p<0.05). Patients: Serum UA was higher with eGFR<60 vs >60 (8.5 vs. 6, P<0.05). Higher TKV correlated with lower eGFR (R2 0.24, P=0.008). Correlation between higher serum UA and higher total kidney volume (R2=0.02, P=0.003). Fast progressors had higher TKV (1523 vs 583, P=0.003), lower eGFR (65 vs 91, P=0.005) and higher serum UA (8.1 vs 5.5, P<0.01) than slow progressors. Serum XO activity was the same between eGFR>60 vs <60 (8.5 vs 6.3,NS). Correlation between higher serum XO and lower eGFR showed a trend (R2=0.08, P=0.07). No correlation between serum XO and TKV (R2=0.009, NS). XO activity was the same in fast and slow progressors (7.7 vs 9.2, P=NS). Conclusion: In summary, in rodents with PKD, there was no correlation between increased serum or kidney XO activity and cyst index. In PKD patients there was a trend towards higher serum XO and lower GFR. In conclusion, serum XO needs to be measured in a larger group of patients from the HALT-PKD study. Funding: Commercial Support - Xortx Therapeutics inc
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".