Mass Spectrometry of Minimal Change Disease and Focal Segmental Glomerulosclerosis
Bibliographic record
Abstract
Introduction The relation between minimal change disease (MCD) and primary focal segmental glomerulosclerosis (pFSGS) remains debatable, and recent discovery of anti-nephrin and anti -slit antibodies, supports the hypothesis of a continuum disease. However, the overall expression of podocyte proteins in these disease states is not known. Methods In this observational proteomic study, we used laser microdissection and mass spectrometry (LMD/MS) to determine the proteomic profile of podocyte proteins in kidney biopsies of adult patients with MCD (n=6), pFSGS (n=7), secondary FSGS (sFSGS) (n=10), and genetic FSGS (gFSGS) (n=6). Time zero kidney transplant (T0) (n=6), IgA nephropathy (n=5) and membranous nephropathy (MN) (n=8) served as non-proteinuric and proteinuric controls, respectively. MS results are expressed as total spectrum (TSC) representing the relative abundance of the specific protein. Immunofluorescence (IF) staining assessing nephrin and podocin were also performed. Results LMD/MS show moderate baseline TSC of podocyte protein NPHS1 (nephrin), NPHS2 (podocin), CD2AP, ACTN4, INF2, and DAG1 in time zero kidney transplant and MN controls. On the other hand, there was a significant loss of all 6 podocyte proteins in MCD, pFSGS, sFSGS, and gFSGS but not in MN cases. IF staining confirmed podocyte loss of nephrin and podocin in MCD, pFSGS, sFSGS, and gFSGS but not in T0 or MN. Conclusion LMD/MS and IF staining shows significant and comparable loss of podocyte proteins involving the slit diaphragm and actin cytoskeleton in MCD, pFSGS, sFSGS, and gFSGS suggesting a common final pathway of podocyte injury. Surprisingly, despite similar degrees of proteinuria, MN was not associated with significant loss of podocyte proteins.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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) | 0.000 | 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 teacher head, 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".