Platelet-Dependent Inflammatory Dysregulation in Patients with Stages 4 or 5 Chronic Kidney Disease: A Mechanistic Clinical Study.
P2Y12 inhibitors
aspirin
chronic kidney disease
inflammation
leukocytes
monocytes
platelets
Journal
Kidney360
ISSN: 2641-7650
Titre abrégé: Kidney360
Pays: United States
ID NLM: 101766381
Informations de publication
Date de publication:
29 12 2022
29 12 2022
Historique:
received:
22
08
2022
accepted:
04
10
2022
entrez:
2
1
2023
pubmed:
3
1
2023
medline:
4
1
2023
Statut:
epublish
Résumé
Chronic kidney disease (CKD) is characterized by dysregulated inflammation that worsens with CKD severity. The role of platelets in modulating inflammation in stage 4 or 5 CKD remains unexplored. We investigated whether there are changes in platelet-derived thromboinflammatory markers in CKD with dual antiplatelet therapy (DAPT; aspirin 81 mg/d plus P2Y12 inhibitor). In a mechanistic clinical trial, we compared platelet activation markers (aggregation and surface receptor expression), circulating platelet-leukocyte aggregates, leukocyte composition (monocyte subtypes and CD11b surface expression), and plasma cytokine profile (45 analytes) of non-CKD controls ( Patients with CKD demonstrated a reduced mean platelet count, elevated mean platelet volume, reduced platelet-leukocyte aggregates, reduced platelet-bound monocytes, higher total non-classic monocytes in the circulation, and higher levels of IL-1RA, VEGF, and fractalkine (all Attenuated interactions between platelets and leukocytes in the CKD state coincided with no change in platelet activation status, an altered differentiation state of monocytes, and heightened inflammatory markers. Platelet-derived cytokines were one of the central cytokines in patients with CKD that were tightly correlated with others. DAPT had multifaceted effects on thromboinflammation, suggesting that there is platelet-dependent and -independent inflammation in stage 4 or 5 CKD.
Sections du résumé
Background
Chronic kidney disease (CKD) is characterized by dysregulated inflammation that worsens with CKD severity. The role of platelets in modulating inflammation in stage 4 or 5 CKD remains unexplored. We investigated whether there are changes in platelet-derived thromboinflammatory markers in CKD with dual antiplatelet therapy (DAPT; aspirin 81 mg/d plus P2Y12 inhibitor).
Methods
In a mechanistic clinical trial, we compared platelet activation markers (aggregation and surface receptor expression), circulating platelet-leukocyte aggregates, leukocyte composition (monocyte subtypes and CD11b surface expression), and plasma cytokine profile (45 analytes) of non-CKD controls (
Results
Patients with CKD demonstrated a reduced mean platelet count, elevated mean platelet volume, reduced platelet-leukocyte aggregates, reduced platelet-bound monocytes, higher total non-classic monocytes in the circulation, and higher levels of IL-1RA, VEGF, and fractalkine (all
Conclusions
Attenuated interactions between platelets and leukocytes in the CKD state coincided with no change in platelet activation status, an altered differentiation state of monocytes, and heightened inflammatory markers. Platelet-derived cytokines were one of the central cytokines in patients with CKD that were tightly correlated with others. DAPT had multifaceted effects on thromboinflammation, suggesting that there is platelet-dependent and -independent inflammation in stage 4 or 5 CKD.
Identifiants
pubmed: 36591354
doi: 10.34067/KID.0005532022
pii: 02200512-202212000-00009
pmc: PMC9802560
doi:
Substances chimiques
Cytokines
0
Platelet Aggregation Inhibitors
0
Tumor Necrosis Factor-alpha
0
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2036-2047Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR003108
Pays : United States
Informations de copyright
Copyright © 2022 by the American Society of Nephrology.
Déclaration de conflit d'intérêts
J.M. Arthur reports consultancy for Nephraegis Therapeutics and Travere Therapeutics; honoraria from Travere Pharmaceuticals; and an advisory or leadership role for Kidney360. All remaining authors have nothing to disclose.
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