Urine Complement Activation Products in Lupus Nephritis
Bibliographic record
Abstract
Background: 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 complementdirected therapies. In this investigation, urine CAPs levels were measured, and associations with kidney injury were determined. Methods: 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. Results: The results are summarized in the Table. 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. Conclusions: 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. Funding: Private Foundation Support - Parameter Spearmanr P Value 95% Confidence Interval Ba C5a C5b-9 Ba C5a C5b-9 Ba C5a C5b-9 Activity index 0.31 0.25 0.37 0.0004 0.005 <0.0001 0.14,0.47 0.07,0.41 0.20,0.52 •Endocapailary Hypercell 0.25 0.23 0.36 0.005 <0.01 <0.0001 0.07,0.41 0.05,0.39 0.19,0.51 • Hyaline Deposits 0.19 0.23 0.23 0.036 0.018 0.0094 0.008,0.36 0.031,0.38 0.05,0.39 • PMN/Karyorrhexis 0.18 0.18 0.32 0.044 0.044 0.0003 0.0005,0.35 0.0004,0.35 0.15,0.47 • Necrosis 0.19 0.21 0.027 0.42 0.017 0.018,0.37 0.034,0.38 • Crescents 0.21 0.21 0.019 0.06 0.004 0.03,0.38 0.08,0.42 • Interstitial Inflammation 0.35 0.26 0.27 <0.0001 0.003 0.002 0.18,0.50 0.08,0.42 0.097,0.43 Chronicity Index 0.29 0.19 0.0005 0.022 0.22 0.13,0.44 0.02,0.35 • Glomerulosclerosis 0.23 0.36 0.73 • Fibrous Crescents 0.94 0.37 0.83 • Tubular Atrophy 0.31 0.24 0.0002 0.031 0.17 0.15,0.45 0.079,0.39 • Interstitial Fibrosis 0.31 0.24 0.0002 0.031 0.16 0.15,0.45 0.079,0.39 Proteinuria 0.41 0.54 0.42 <0.0001 <0.0001 <0.0001 0.25,0.54 0.42,0.66 0.27,0.55 Serum Creatinine 0.51 0.31 <0.0001 0.0001 0.61 0.38,0.63 0.15,0.46 Complement C3 -0.31 0.0002 0.06 0.16 -0.46,-0.15 Complement C4 0.09 0.18 0.25 Urine Ba 0.71 0.46 <0.0001 <0.0001 0.62,0.78 0.31,0.58 Urine C5a 0.68 <0.0001 0.59,0.76
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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".