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Am J Physiol Renal Physiol 294: F220-F228, 2008. First published August 1, 2007; doi:10.1152/ajprenal.00279.2007
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Differential effects of dialysis and ultrafiltrate from individuals with CKD, with or without diabetes, on platelet phosphatidylserine externalization

Yingjie Wang,1 Werner Beck,2 Reinhold Deppisch,2 Sally M. Marshall,1 Nicholas A. Hoenich,1 and Michael G. Thompson1

1Faculty of Medical Sciences, Newcastle University, Newcastle-Upon-Tyne, United Kingdom; and 2Gambro Corporate Research, Hechingen, Germany

Submitted 19 June 2007 ; accepted in final form 30 July 2007

Individuals with chronic kidney disease (CKD) and/or diabetes mellitus (DM) are at increased risk of cardiovascular events and have elevated externalization of phosphatidylserine (PS; which propagates thrombus formation) in a small subpopulation of platelets. The purpose of this study was to examine the effect of 1) removing uremic toxins by hemodialysis on PS externalization in patients with either CKD or CKD and DM and 2) ultrafiltrate (UF) from these individuals on PS externalization in healthy platelets. PS externalization was quantified by a fluorescence-activated cell sorter using annexin V in platelet-rich plasma. PS externalization was elevated threefold in CKD patients and returned to basal values during 3-h hemodialysis. In contrast, it was elevated fivefold in individuals with CKD and DM and was still threefold above control after 3-h treatment. UF significantly increased PS externalization in a small subpopulation of platelets from healthy controls. The effect of UF from individuals with CKD and DM was significantly greater than that from patients with CKD alone, and the responses were partially inhibited by the protein kinase C{delta} (PKC{delta}) inhibitor rottlerin and the 5-hydroxytryptamine (5-HT)2A/2C receptor antagonist ritanserin. The data suggest that uremic toxins present in UF mediate PS externalization in a small subpopulation of platelets, at least in part, via the 5-HT2A/2C receptor and PKC{delta} and demonstrate that DM further enhances platelet PS externalization in CKD patients undergoing hemodialysis. This may explain, at least in part, the additional increase in vascular damage observed in CKD patients when DM is present.

cell signaling; thrombosis; 5-HT2A/2C receptors


Address for reprint requests and other correspondence: M. G. Thompson, Framlington Place, Faculty of Medical Sciences, Newcastle Univ., Newcastle-Upon-Tyne, UK NE2 4HH (e-mail: m.g.thompson{at}ncl.ac.uk)






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