Urine Complement Factor Ba Is Associated with AKI in Critically Ill Children
Bibliographic record
Abstract
Key Points Complement activation, specifically factor B, is implicated in AKI pathogenesis in animal models. Urine Ba (an activation fragment of factor B) was significantly higher in critically ill children with stage 3 AKI and sepsis-AKI. If larger studies show similar association between urine Ba and AKI severity, clinical trials of factor B inhibition are warranted. Background: Critically ill children with AKI have high morbidity and mortality rates and lack treatment options. Complement activation is implicated in AKI pathogenesis, which could be treated with complement-targeted therapeutics. We assessed for an association between urine Ba, an activation fragment of the alternative complement pathway, and AKI in a large cohort of critically ill children. Methods: A biorepository of children requiring mechanical ventilation was leveraged. AKI was based on pediatric version of the RIFLE criteria—stage 1: 25% decreased eGFR or urine output (UOP) <0.5ml/kg per hour for 8 hours; stage 2: 50% decreased eGFR or UOP <0.5 ml/kg per hour for 16 hours; stage 3: 75% decreased eGFR or UOP <0.3ml/kg per hour for 24 hours or anuric for 12 hours. ELISAs were performed to quantitate urine Ba values. Log Ba was used in ANOVA with pairwise comparison by the Tukey method. Logistic regression was performed to test the association between urine Ba and AKI diagnosis. Results: Seventy-three patients were included, of which 56 had AKI: 26 (46%) stage 1, 16 (29%) stage 2, and 14 (25%) stage 3. Ba was significantly higher in patients with stage 3 AKI compared with all other stages. Ba was higher in sepsis-associated AKI compared with non–sepsis-associated AKI. Multivariate analysis included urine Ba, urine IL-18, urine NGAL, sepsis, and Pediatric Risk of Mortality Scores-II (an estimate of illness severity) and showed a significant association between urine Ba and AKI (odds ratio 1.57, 95% confidence interval, 1.13 to 2.20; P 0.007). Conclusion: Urine Ba is significantly increased in patients with AKI compared with patients without AKI. In patients with similar illness severity, a doubling of urine Ba level was associated with a 57% increase in AKI diagnosis of any stage. Further studies are needed to study complement inhibition in treatment or prevention of AKI in critically ill children.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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".