Challenging Clinical Practice Guideline Definitions in Childhood Nephrotic Syndrome
Bibliographic record
Abstract
Background: In childhood nephrotic syndrome, definitions of immunosuppression response, frequent relapses (FRNS), and long-term remission are conflicting and not evidence based. Our goal was to define treatment response, FRNS, and long-term remission based on associated disease outcomes. Methods: We included children (6mo-18yr) diagnosed with nephrotic syndrome between 1993-2023 in combined Canadian cohorts. We evaluated different definitions of 1) immunosuppression response, 2) FRNS, including KDIGO and IPNA criteria, and 3) long-term remission. Outcomes were time-to-chronic kidney disease (CKD), relapse count throughout follow-up, and time-to-relapse, analyzed by Cox proportional hazards and negative binomial regression. Results: We included 1114 children with nephrotic syndrome (median 3.8-years at diagnosis, 63% male, median 4.7-year follow-up). Of these, 1054 (95%) were steroid-sensitive, 60 (5%) were steroid-resistant (SRNS), and 73% with SRNS achieved complete remission with steroid-sparing immunosuppression. No child with treatment-responsive SRNS developed CKD. Within 1-year of diagnosis, 281 steroid-sensitive children (27%) were classified with FRNS by KDIGO and 383 (36%) by IPNA criteria. Children with FRNS by IPNA criteria (vs. KDIGO) had a similar number of relapses (adjusted rate ratio 0.95, 95%CI 0.81-1.12) and CKD risk (2% each) but received less steroid-sparing immunosuppression (hazard ratio 0.42, 95%CI 0.32-0.56). Conclusion: Children with SRNS that achieve remission have a similar CKD risk as steroid-sensitive children. Children with FRNS by IPNA and KDIGO criteria experience similar rates of relapse and CKD. This supports defining treatment resistance by response to any immunosuppression and implementation of the IPNA FRNS criteria.Figure. Number of relapses throughout follow up (median 4.6-years), stratified by the number of relapses by a) 6-months, b) 1-year, and c) nephrotic syndrome classification criteria by 1-year after diagnosis
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.132 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.006 | 0.008 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.004 | 0.003 |
| Open science | 0.007 | 0.004 |
| Research integrity | 0.004 | 0.005 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".