Utility of Adult-Derived Biomarkers for Assessment of Kidney Function in Pediatric ANCA-Associated Vasculitis
Bibliographic record
Abstract
Background: In adults with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), measures of ANCA positivity and antigen specificity, estimated glomerular filtration rate (eGFR), and urine proteins are informative of kidney function and aid treatment decisions. Despite aggressive therapy, two-thirds of pediatric AAV patients have persistently reduced renal function. The objective of this study is to evaluate the utility of adult-derived kidney markers in pediatric AAV. Methods: Eligible participants < 18 yrs of age in the ARChiVe/PedVas initiative had a diagnosis of small vessel vasculitis including AAV, ANCA positive pauci-immune glomerulonephritis, and unclassified primary vasculitis. Kidney disease activity was defined by the renal component of the pediatric vasculitis activity score. Kidney function was categorized by eGFR into KDIGO stages. Predictive analysis of ANCA and baseline eGFR for 1- to 2-year outcomes were conducted using adjusted regression models and/or a proportional odds logistic regression model. Concentrations (ELISA) of MCP-1, sCD25, and sCD163 in time-of-diagnosis urine was measured for correlations with baseline and 1-year kidney state using R statistical language. Results: At diagnosis, patients with MPO-ANCA had similar levels of overall disease activity to those with PR3-ANCA but had 2.4 times higher odds of kidney involvement (P = 0.008) and 6.0 times higher likelihood of worse kidney dysfunction (P < 0.001). Time-of- diagnosis eGFR was informative to future kidney function with the odds of worse kidney function at 1-year being 18.2 times higher for children with moderately-severely reduced function at onset. Urine proteins performed poorly as indicators of kidney disease activity at onset and follow up. Conclusion: The results of this study show mixed utility of adult derived biomarkers for use in the pediatric population, with severe kidney disease at onset and function over the first 1-year being best informed, respectively, by MPO-ANCA seropositivity and baseline eGFR. The study illustrates the need for pediatric AAV-focused studies for novel kidney biomarker discovery. 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 | 0.003 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.001 | 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".