Treatment of Childhood-onset Proliferative Lupus Nephritis in the 21st Century: A Call to Catch Up With the Evidence
Bibliographic record
Abstract
Proliferative lupus nephritis (PLN) is associated with significant morbidity, mortality, and kidney failure, especially in childhood-onset PLN (cPLN). Therefore, it is important to treat it promptly and aggressively, while being cognizant of the risk-benefit ratio and side effects of therapies. In 1986, a study that dramatically changed the treatment of PLN was the “National Institutes of Health (NIH) protocol,” which used intravenous (IV) cyclophosphamide (CYC) pulse therapy and became the standard of care for patients with adult-onset (aPLN) and cPLN (none of the patients had cPLN).1 The major limitation to the use of CYC is its side effects, particularly infections, leukopenia, malignancy, and premature ovarian failure; this led to the advent of the lower cumulative dose EuroLupus protocol.2 Subsequently, multiple large randomized controlled trials (RCTs) showed that mycophenolate mofetil (MMF) was as efficacious as IV CYC, with a better safety profile.3,4,5,6 In this issue of The Journal of Rheumatology , Cannon et al7 conducted a Web-based, cross-sectional survey of North American physicians on their prescribing practices for the treatment of cPLN, in the spring of 2020. Preferences for and perceptions of the 2 commonly used IV CYC protocols to treat LN was the primary aim of the study. One must wonder why this was the aim, rather than focusing on the use of IV CYC vs MMF, with the choice of IV CYC protocol as a secondary aim. The survey was distributed through Childhood Arthritis and Rheumatology Research Alliance (CARRA), an international research organization where 90% of North American pediatric rheumatologists are members (185 respondents), and the Pediatric Nephrology Research Consortium (40 respondents) to capture both pediatric rheumatologists and nephrologists who might look after patients with cPLN. This was a follow-up article to the CARRA initial consensus treatment plan (CTP) … Address correspondence to Dr. E.D. Silverman, The Hospital for Sick Children, Division of Rheumatology, 555 University Avenue, Toronto, ON M5G 1X8, Canada. Email: earl.silverman{at}sickkids.ca.
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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 | 0.011 | 0.037 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.006 | 0.008 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.006 | 0.010 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".