Chronic Kidney Disease Severity Is Associated With Selective Expansion of a Distinctive Intermediate Monocyte Subpopulation
Notice bibliographique
Résumé
Chronic kidney disease (CKD) affects 11-13% of the world’s population and greatly increases risk of cardiovascular disease (ASCVD) and death. It is characterized by systemic inflammation and disturbances in the blood leukocytes that remain incompletely understood. In particular, abnormalities in the numbers and relative proportions of the three major monocyte subsets - classical, intermediate and non-classical – are described in CKD and end-stage renal disease. In this study, we characterized absolute numbers of blood leukocyte subtypes in adults with renal function varying from normal to advanced CKD. The primary aim was to identify monocyte subpopulations that associated most closely with current estimated glomerular filtration rate (eGFR) and subsequent rate of eGFR decline. Leucocyte and monocyte populations were enumerated by multi-colour flow cytometry of whole blood and peripheral blood mononuclear cell (PBMC) samples from adults with CKD stage 1-5 (n=154) and healthy adults (n=33). Multiple-linear regression analyses were performed to identify associations between numbers of leucocyte and monocyte populations and clinical characteristics including eGFR and rate of eGFR decline with adjustment for age and gender. In whole blood, total monocyte and neutrophil, but not lymphocyte, numbers were higher in adults with CKD 1-5 compared to CKD 0 and were significantly associated with current eGFR even following correction for age. In PBMC, classical and intermediate monocyte numbers were higher in CKD 1-5 but only intermediate monocyte numbers were significantly associated with current eGFR in an age-corrected analysis. When intermediate monocytes were further sub-divided into those with mid- and high-level expression of class II MHC (HLA-DRmid and HLA-DRhi intermediate monocytes) it was found that only DRhi intermediate monocytes were increased in number in CKD1-5 compared to CKD 0 and were significantly associated with eGFR independently of age among the total (CKD 0-5) study cohort as well as those with established CKD (CKD 1-5). Furthermore, blood number of DRhi intermediate monocytes alone proved to be significantly associated with subsequent rate of renal functional decline. Together, our data confirm neutrophil and monocyte subset dysregulation in CKD and identify a distinct subpopulation of intermediate monocytes that is associated with higher rate of loss of kidney function.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».