Steroid-sparing drugs in children and young adults with nephrotic syndrome: a target trial emulation
Bibliographic record
Abstract
BACKGROUND: Children and young adults with nephrotic syndrome are commonly treated with steroid-sparing immunosuppressive medications. Rituximab is increasingly used in frequently relapsing disease, but the real-world comparative effectiveness of rituximab and calcineurin inhibitors is unclear. METHODS: Using target trial methods, we emulated a pragmatic randomized controlled trial using observational data from two prospective nephrotic syndrome cohorts. We included children and adults (aged 1-40 years) with steroid-sensitive nephrotic syndrome that first initiated rituximab or calcineurin inhibitor treatment during follow-up. Randomization was emulated using overlap weighting of propensity scores for treatment assignment. The primary outcome was time-to-relapse, analyzed by weighted Cox proportional hazards models. Secondary outcomes were relapse counts, subsequent immunosuppressive treatment, kidney function, hypertension and all-cause mortality. RESULTS: Of 372 eligible participants, 104 initiated rituximab and 268 initiated calcineurin inhibitors. Baseline characteristics were balanced after propensity score weighting. Mean age at medication initiation was 13.2 years, 61% were male and 69% had received prior steroid-sparing medications. Throughout a median 4.9-year (quartile 1-3, 2.0-7.2) follow-up, relapses occurred in 58 participants (56%) treated with rituximab and 209 (78%) treated with calcineurin inhibitors. There was no significant difference in time-to-relapse after rituximab vs calcineurin inhibitor treatment [weighted hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.59-1.38]. There were also no significant differences in relapse rates or kidney function decline. Participants treated with rituximab were at lower risk of developing hypertension (weighted HR 0.24, 95% CI 0.08-0.79). CONCLUSIONS: Using real-world data, there was no difference in relapse rates after rituximab vs calcineurin inhibitors among children and young adults with steroid-sensitive nephrotic syndrome. Steroid-sparing immunosuppression selection should be a shared decision, considering medication-specific side effects, costs, access, duration and adherence.
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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 | 0.038 | 0.042 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.004 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".