Voclosporin Induces Systemic Lipidomic Alterations: Implications in the Remission of Lupus Nephritis
Bibliographic record
Abstract
Background: Voclosporin is a novel calcineurin inhibitor indicated for the treatment of adults with active lupus nephritis (LN). Cardiovascular disease (CVD) is a major cause of morbidity and mortality in SLE patients, and LN is an independent CVD risk factor. The AURORA 1 trial showed favorable renal clinical response and changes in traditional lipoproteins with voclosporin. We hypothesize that the beneficial therapeutic response is mediated in part by alteration in circulating lipids. Methods: In a lipidomic analysis, 918 serum lipids in 14 classes from baseline and week 52 of randomly selected participants from control (placebo) (N=30) and voclosporin (N=28) arms of the AURORA 1 trial (ClinicalTrials.gov, NCT03021499; EudraCT, 2016-004045-81) were compared. All patients received MMF and low-dose steroids. The difference of lipids at week 52 from baseline was calculated, z-score standardized, and used in mixed linear models. Results: The alterations of lipid class levels were assessed as a function of voclosporin effect and by achievement of either complete renal response (CRR) or partial renal response (PRR) (Table). Voclosporin and renal clinical response (CRR or PRR) contributed to decline in CERs and TAGs and increase in DCERs and PIs independent of each other. Results indicate the additive effects of voclosporin and renal clinical response on alteration of corresponding lipids. Voclosporin, CRR and PRR were independently associated with alteration of PC(C16), PIs, and TAGs. An integrative analysis showed significant correlations between saturated DAGs and MAGs (C>16), TAGs, SMs, CERs, unsaturated PEPs, and palmitoyl PCs(C16) after controlling for CRR or PRR. Conclusions: CERs, DCERs, PIs, and TAGs are altered by voclosporin. Alterations of PC, PI and TAGs correlate with renal outcome independent of voclosporin. Collectively, these findings suggest that voclosporin reduces lipogenesis by decreasing incorporation of fatty acid precursors, and a favorable therapeutic response is mediated in part by promotion of change in corresponding lipid class. Funding: Commercial Support - Aurinia Pharmaceuticals Inc.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".