Bibliographic record
Abstract
Introduction: Primary hyperoxaluria type 1 (PH1) is a genetic disorder resulting in excess hepatic oxalate production, which can lead to urolithiasis, systemic oxalosis, nephrocalcinosis (NC), and ultimately, chronic kidney disease/kidney failure. 1 Lumasiran, a liver-directed RNA interference therapeutic that reduces urinary oxalate (UOx) levels, demonstrated sustained efficacy with an acceptable safety profile over 12 months in infants and young children aged <6 years with PH1 participating in ILLUMINATE-B (NCT03905694). 2 Our objective was to evaluate outcomes of lumasiran treatment through Month 30 of ILLUMINATE-B.Methods: ILLUMINATE-B is an ongoing, phase 3, multinational, open-label, singlearm study.Eligible patients had a confirmed PH1 diagnosis, were <6 years old at study entry, had an eGFR >45 mL/min/1.73m 2 if ≥12 months old or normal serum creatinine if <12 months old, and UOx:creatinine (Cr) ratio greater than upper limit of normal.A primary analysis was conducted at six months; patients are now in an extension period of up to 54 months.Changes in NC and kidney stone event rates were exploratory endpoints.Results: All 18 patients enrolled in ILLUMINATE-B entered the extension period and remain in the study.At month 30, the mean percent reduction from baseline in spot UOx:Cr ratio with lumasiran treatment was 76%.Mean percent reduction in plasma oxalate was 42% from baseline to month 30.eGFR remained relatively stable through month 30.In 14 patients with NC at baseline, NC grade improved in 86% (12/14) at month 24; no patient worsened.Of the four patients with no baseline NC, all remained stable at month 24.Kidney stone event rates remained low through month 30.The most common lumasiran-related adverse events were mild, transient injection-site reactions (three patients [17%]).Conclusions: In infants and young children with PH1, lumasiran treatment resulted in sustained reductions in urinary and plasma oxalate through month 30, with an acceptable safety profile.Previous observations of stable kidney function and low kidney stone event rates were maintained through month 30, while improvements in NC grade were maintained through month 24.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.309 | 0.147 |
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".