Immunodeposits and Urinary Complement Activation Fragments Are Linked to IgAN Activity and Progression: Findings from the CureGN Study
Bibliographic record
Abstract
Background: Small cohorts have reported variable associations between immunodeposits and complement activation with clinical outcomes in IgA nephropathy (IgAN). In parallel, therapeutic trials show encouraging results using complement inhibition. We sought to confirm the value of immunofluorescence findings and urinary complement fragments in defining disease activity and progression. Methods: Using IgAN patients with available pathology assessment from the CureGN cohort, we tested associations between immunoglobulins and C3 distribution and intensity by immunofluorescence with the Oxford MEST-C score, urinary membrane attack complex (sC5b9), proteinuria, and survival from a combined outcome; kidney failure or 40% decline in eGFR. Results: We analyzed 247 IgAN patients, including 115 incident subjects enrolled within 6 months of kidney biopsy. IgA and C3 staining intensity were associated with mesangial hypercellularity. Localization of IgM, C3, and IgA deposits along capillaries was associated with endocapillary hypercellularity, cellular crescents, and foot process effacement. In incident subjects, urinary sC5b9 showed associations with global endocapillary hypercellularity, crescent formation, and IgM and C3 deposition along capillaries. While immunodeposits were not associated with a combined outcome, urinary sC5b9 was. When adjusting for the level of proteinuria, significant interaction existed (p=0.009), indicating elevated urinary sC5b9 correlated with a reduced outcome in those with elevated proteinuria (illustrated by Kaplan Meier curves using dichotomizing urinary measurements). Conclusion: In IgAN, intensity and localization of immunodeposits correlate with mesangial, endocapillary, and extracapillary hypercellularity and the level of urinary sC5b9. In turn, the urinary sC5b9 is independently associated with eGFR loss.
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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 | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| 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".