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1101 Urine complement activation products in lupus nephritis

2022· article· en· W4313460612 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueInnate Immunity · 2022
Typearticle
Languageen
FieldMedicine
TopicSystemic Lupus Erythematosus Research
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordsLupus nephritisMedicineProteinuriaComplement systemUrineRenal biopsyCreatinineInternal medicineKidneyGastroenterologyPathologyBiopsyImmunologyAntibodyDisease

Abstract

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<h3>Background</h3> Complement activation plays a critical role in the development of kidney injury during lupus nephritis (LN). Clinical trials targeting the complement pathway are now underway in LN. It is therefore important to understand the relationship between intra-renal complement activation and kidney histology in LN, and whether complement activation products (CAPs) can serve as biomarkers to guide complement-directed therapies. In this investigation, urine CAPs levels were measured, and associations with kidney injury were determined. <h3>Methods</h3> A cohort of 149 patients had urine and blood collected at the time of kidney biopsy for suspected LN. The CAPs C5a, C5b-9, and factor Ba were measured in the urine by ELISA. Biopsies were examined by routine histology, and the NIH activity and chronicity indexes (AI,CI) were calculated by two nephropathologists. CAPs levels were correlated with clinical and histologic data using the spearman correlation r. <h3>Results</h3> The results are summarized in the table 1. The highest levels of CAPs were found in patients with proliferative or proliferative plus membranous LN, with lower levels in pure class II and V. All three urine CAPs correlated with AI, but the strongest correlation was between C5b-9 and AI. Only Ba and C5a correlated with CI, but this correlation was, at best, modest. All CAPs correlated with proteinuria, while only Ba and C5a correlated with serum creatinine. <h3>Conclusion</h3> Urine C5b-9 was the best measure of histologic activity in LN. Given the size of the C5b-9 complex, it is unlikely to be filtered, even by glomeruli with a damaged glomerular permeability barrier. Urine C5b-9 therefore only reflects intra-renal complement activity. C5a and Ba associated modestly with active lesions, as well as kidney damage, likely accounting for their association with serum creatinine. We suggest levels of urine C5b-9 could be used to follow the success of anti-complement therapies in mitigating intra- renal complement activation in LN.

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Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.428
Threshold uncertainty score0.994

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.048
GPT teacher head0.316
Teacher spread0.267 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it