{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:31:18Z","timestamp":1786480278727,"version":"build-2736575974"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2022,12]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n Patients with CKD have a reduced platelet count, higher platelet volume, reduced platelet-leukocyte interactions, and higher nonclassic monocytes.<\/jats:p>\n <\/jats:list-item>\n \n Platelet-derived cytokines are one of the central cytokines in correlation analysis of 45-cytokine panel in patients with stages 4 or 5 CKD.<\/jats:p>\n <\/jats:list-item>\n \n Antiplatelet drugs had multifaceted effects on thromboinflammation, suggesting platelet-dependent and -independent inflammation in CKD.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n 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).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n 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 (\n n<\/jats:italic>\n =26) and CKD outpatients (\n n<\/jats:italic>\n =48) with a glomerular filtration rate (GFR) <30 ml\/min per 1.73 m\n 2<\/jats:sup>\n on 2 weeks of DAPT.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 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\n P<\/jats:italic>\n <0.05). There were no differences in platelet activation markers between CKD and controls. Although DAPT reduced platelet aggregation in both groups, it had multifaceted effects on thromboinflammatory markers in CKD, including a reduction in PDGF levels in all CKD individuals, reductions in IL-1\n \u03b2<\/jats:italic>\n and TNF-\n \u03b1<\/jats:italic>\n levels in select CKD individuals, and no change in a number of other cytokines. Significant positive correlations existed for baseline IL-1\n \u03b2<\/jats:italic>\n , PDGF, and TNF-\n \u03b1<\/jats:italic>\n levels with older age, and for baseline TNF-\n \u03b1<\/jats:italic>\n levels with presence of diabetes mellitus and worse albuminuria. Mean change in IL-1\n \u03b2<\/jats:italic>\n and PDGF levels on DAPT positively correlated with younger age, mean change in TNF-\n \u03b1<\/jats:italic>\n levels with higher GFR, and mean changes in PDGF, and TRAIL levels correlated with worse albuminuria. Minimum spanning trees plot of cytokines showed platelet-derived CD40L had a large reduction in weight factor after DAPT in CKD. Additionally, platelet-derived IL-1\n \u03b2<\/jats:italic>\n and PDGF were tightly correlated with other cytokines, with IL-1\n \u03b2<\/jats:italic>\n as the hub cytokine.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.34067\/kid.0005532022","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T18:25:11Z","timestamp":1666808711000},"page":"2036-2047","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":13,"title":["Platelet-Dependent Inflammatory Dysregulation in Patients with Stages 4 or 5 Chronic Kidney Disease: A Mechanistic Clinical Study"],"prefix":"10.34067","volume":"3","clinical-trial-number":[{"clinical-trial-number":"nct03649711","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02539160","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Adam","family":"Corken","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Arkansas for Medical Sciences, Little 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Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Smyth","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton L.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5901-391X","authenticated-orcid":false,"given":"Terry O.","family":"Harville","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, 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