Clinical and Histologic Predictors of Kidney Outcomes in C3 Glomerulopathy and Idiopathic Membranoproliferative GN
Bibliographic record
Abstract
Key Points Lower eGFR, paraprotein presence, and interstitial fibrosis were associated with a higher risk of kidney outcome. Native disease (versus recurrence post-transplantation), White ethnicity, and lower C4 levels were associated with a lower risk of kidney outcome. A 50% reduction in proteinuria from baseline to a value <1 g/d was associated with a lower risk of kidney outcome. Background C3 glomerulopathy (C3G) is a rare disease caused by abnormalities in the alternative complement pathway with significant overlap with idiopathic immune complex membranoproliferative GN (IC-MPGN). The risk factors of kidney outcomes in these conditions remain controversial, limited by small studies. We aimed to identify and assess risk factors associated with kidney outcomes. Methods Using a cohort of 225 patients with C3G or idiopathic IC-MPGN from three international centers, we evaluated the association between clinical and histologic variables and a composite outcome of a 30% decline in eGFR or ESKD, using Cox proportional hazards models. A prediction model was derived and internally validated through bootstrap resampling. Results In a multivariable model, lower eGFR, paraprotein presence, and interstitial fibrosis were associated with a higher outcome risk, whereas native disease (versus recurrence post-transplantation), White ethnicity, and lower C4 levels were associated with lower risk. The prediction model including these variables performed well (R 2 D : 53%, C-statistic: 0.84 [95% confidence interval, 0.82 to 0.86], integrated calibration index: 0.31) and maintained robustness after internal validation. A 50% reduction in proteinuria from baseline to a value <1 g/d was associated with a lower risk of outcome independent of other risk factors (hazard ratio, 0.35; 95% confidence interval, 0.12 to 0.97). Conclusions Our study evaluated the baseline clinical and histologic parameters associated with kidney outcomes using the largest C3G/idiopathic IC-MPGN cohort to date. These factors were included in a prediction model to assess individual patient risk. Our results provide an evidence-based definition of proteinuria remission that can be used for patient care and in clinical trials. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2025_08_27_CJASNAugust.20.8.82.mp3
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.006 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".