036. USCD163 IS AN EARLY PREDICTOR OF TREATMENT RESPONSE IN CRESCENTIC GLOMERULONEPHRITIS
Bibliographic record
Abstract
Background: An unmet need exists in the personalized guidance of immunosuppressive therapy intensity. Urine sCD163 is a marker of glomerular crescent macrophage activation with prior work demonstrating increased usCD163 levels in renal ANCA-associated vasculitis (AAV) at diagnosis and flare. Methods: We prospectively enrolled patients with crescentic glomerulonephritis (CGN) undergoing cytotoxic induction therapy and obtained serial detailed clinical phenotypic information and urine samples. Those who did not undergo renal biopsy had met ACR or Chapel Hill Consensus Conference definition of AAV with clinical evidence of renal activity (increase in serum creatinine >30%, new/worse hematuria or proteinuria). usCD163 was measured by ELISA and results normalized to urine creatinine. Refractory disease was defined as per EULAR guidelines with lack of treatment response despite adequate immunosuppression and persistent positive BVAS score. Results: Urine samples and clinical data were obtained at 181 clinical encounters from 33 patients, of whom 25 (76%) had AAV, 6 (18%) had anti-glomerular basement membrane disease and 2 (6%) had other CGN. Mean eGFR at enrollment was 26.5mls/min (SD 18.2). Induction therapy comprised corticosteroids plus cyclophosphamide in 45%, rituximab in 27% and both cyclophosphamide and rituximab in 27%. Median usCD163 level was 1115ng/mmol (IQR 426.7-1804ng/mmol), 634.2ng/mmol (IQR 355.2-1365), 267.9ng/mmol (IQR 140.8-412.5) and 242ng/mmol (IQR 115.2-994.2) at diagnosis, one, three and six months respectively. In those subsequently diagnosed as having refractory disease the usCD163 value at one month was predictive of refractory disease with median usCD163 of 463.7ng/mmol (IQR 182.7- 592.4ng/mmol) and 2021ng/mmol (IQR 1499-2943ng/mmol) in treatment responsive and refractory patients respectively (p < 0.001). We derived an optimal cut off based on month one usCD163 values of greater than 1115ng/mmol, with sensitivity and specificity of 100%. usCD163 level was higher at the time of switch to maintenance therapy in those receiving rituximab induction compared to cyclophosphamide induction with median usCD163 values at time of switch of 382.7ng/mmol (IQR 168.2-889.7ng/mmol) and 142.2ng/mmol (IQR 77.6-243.9ng/mmol), respectively (p = 0.02). Conclusion: usCD163 may aid in the early identification of refractory disease. Disclosures: This work was supported by the Meath Foundation (grant 203170), Irish Health Research Board (grant HRA-POR-2015-1205 and NSAFP-2013-02), and Science Foundation Ireland (11/Y/B2093).
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".