Contribution of the Endothelium to the Glomerular Permselectivity Barrier in Health and Disease
Bibliographic record
Abstract
BACKGROUND: The endothelium that lines glomerular capillaries shares many properties with endothelial cells in general, but unlike most endothelial cells, it is extremely flat and densely perforated by transendothelial cell pores, the fenestrae. Until recently, it was believed that the fenestrae allow free passage of large proteins, and that the glomerular endothelium contributes little to the permselectivity of the glomerular capillary wall. METHODS: Key studies addressing the nature of the glomerular capillary endothelium and its contribution to glomerular permselectivity were reviewed. RESULTS: Glomerular endothelial cell flattening and fenestrae formation requires signals from differentiated podocytes, and from the glomerular basement membrane. Deletion of VEGF-A from podocytes prevents flattening and fenestration of glomerular endothelium. Application of VEGF-A to endothelial cells in vivo stimulates fenestrae formation, and neutralization of VEGF-A by soluble VEGF receptor 1 (sFlt-1) or anti-VEGF antibodies results in loss of glomerular fenestrae, and proteinuria. Neutralizing TGF-beta1 antibodies, deletion of laminin alpha3 in mice or laminin beta3 in humans cause similar defects. The glomerular endotheliosis lesion of pre-eclampsia is due to the placenta-derived inhibitors sFlt-1 and sEndoglin, which block the VEGF-A/VEGF receptor and TGF-beta/endoglin signaling, respectively, causing the loss of glomerular endothelial cell fenestrae, cell swelling and proteinuria. The glomerular endothelium is covered by a glycocalyx that extends into the fenestrae and by a more loosely associated endothelial cell surface layer of glycoproteins. Mathematical analyses of functional permselectivity studies have concluded that the glomerular endothelial cell glycocalyx and its associated surface layer account for the retention of up to 95% of proteins within the circulation. Furthermore, the fenestrae are critical for the maintenance of the high hydraulic conductivity of the glomerular capillary wall, and their loss results in a reduction in the glomerular filtration rate. CONCLUSIONS: Loss of GFR and proteinuria can result from glomerular endothelial cell injury.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".