CLINICAL AND HISTOLOGICAL PREDICTORS OF RENAL FUNCTION LOSS IN LUPUS NEPHRITIS: RESULTS FROM THE ACCELERATING MEDICINES PARTNERSHIP IN RA/SLE NETWORK
Bibliographic record
Abstract
O040 / #227 Topic: AS15 - Lupus Nephritis-Clinical ABSTRACT CONCURRENT SESSION 06: LUPUS NEPHRITIS – CLINICAL OUTCOMES, PREDICTION AND THERAPY 23-05-2025 1:40 PM - 2:40 PM Background/Purpose Kidney survival is the ultimate outcome in lupus nephritis (LN), but predictors remain inadequately studied due to the need for long-term follow-up. This study aimed to identify clinical and histological predictors of kidney survival in LN. Methods The Accelerating Medicines Partnership (AMP) enrolled patients undergoing a clinically indicated (UPCR >0.5) kidney biopsy with resultant histology class II, III, IV, and/or V lupus nephritis (LN). Clinical and demographic features were collected from the time of diagnostic biopsy. Response was defined at 1 year for patients with baseline UPCR >1. Histological features were centrally scored. Kidney function loss was defined as a sustained 40% decline in estimated glomerular filtration rate (eGFR) or progression to end-stage kidney disease (ESKD). A Cox proportional hazard model was employed to identify predictors. Results We included 172 patients with a median follow-up time of 4.6 years (range 0.5-7.8), of whom 153 (89%) had >3 years follow-up. Clinical and demographic features are summarized in Table 1. A third of patients (56/172) developed eGFR loss with a median time to event of 2.6 years (range 0.13-7.1). Predictors of eGFR loss at time of biopsy included lower eGFR (especially eGFR <30 ml/min, HR 5.4), repeat biopsy status (HR 2.5), and NIH Chronicity Index (histological damage, HR 1.3 per unit) (Table 1). Sex, race, age, BMI, proteinuria, ISN class, NIH Activity Index, C3, C4, and anti-dsDNA were not associated with eGFR loss. Among histological features, an NIH Chronicity Index >2 (HR 2), glomerulosclerosis (HR 1.9), interstitial fibrosis (HR 2), tubular atrophy (HR 1.9), and interstitial inflammation (HR 2-but p=0.06), but not fibrous crescents or any of the NIH Activity Index glomerular features, were associated with eGFR loss (Table 1). Lack of clinical response at 3, 6, or 12 months was associated with future eGFR loss (Figure 1). Partial response at 12 months had higher risk of eGFR loss compared to complete response (HR 10.7), but lower than no response (HR 19). Reductions of UPCR >25% at 3 and >50% at 6 months were protective (HR 0.44-but p=0.11 and 0.3, respectively). Four patients with UPCR <0.5 at 1 year developed eGFR loss (1.8/100 person-years). Table 1. Association of baseline clinical, demographic, and histological features with GFR loss. Figure 1. Association of longitudinal clinical features with GFR loss Conclusions Low baseline eGFR and histological damage, but not activity or ISN class, predicted eGFR loss. Improvement of UPCR was associated with lower risk of eGFR loss, though eGFR loss still occurred in patients in clinical remission (UPCR <0.5) at 1 year. Acknowledgments: This work was funded by the Plank Family Foundation and the Jerome L. Greene Foundation. The Hopkins Lupus Cohort is supported by NIH R01-DK-134625. Additionally, this research was supported by the Accelerating Medicines Partnership® Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP® RA/SLE) Network, a public-private partnership involving AbbVie Inc., Arthritis Foundation, Bristol Myers Squibb Company, Foundation for the National Institutes of Health, GlaxoSmithKline, Janssen Research and Development, LLC, Lupus Foundation of America, Lupus Research Alliance, Merck & Co., Inc. Sharp & Dohme Corp., National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer Inc., Rheumatology Research Foundation, Sanofi, and Takeda Pharmaceuticals International, Inc. The AMP Network aims to develop new methods for identifying and validating promising biological targets for diagnostics and drug development. Funding was provided through grants from the National Institutes of Health (UH2-AR067676, UH2-AR067677, UH2-AR067679, UH2-AR067681, UH2-AR067685, UH2-AR067688, UH2-AR067689, UH2-AR067690, UH2-AR067691, UH2-AR067694, and UM2-AR067678).
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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 | 0.005 |
| 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 | 0.000 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| 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".