438 Platelets, Inflammation and Thrombosis in Chronic Kidney Disease

Abstract

OBJECTIVES/GOALS: Platelets reside at the nexus of thrombosis and inflammation which make them an ideal target of investigation to understand mechanisms underlying chronic kidney disease (CKD)-related inflammatory and thrombotic dysregulation. Our objective is to determine whether a pro-inflammatory state in CKD is exacerbated by platelets. METHODS/STUDY POPULATION: Aim 1 will investigate effects of engineered reduction in the interaction of platelets with leukocytes [by disruption of one of the platelet surface receptor (GPIb-IX)] in the development of CKD in murine models. Aim 2 will investigate effects of platelet inhibitors on the development of CKD in murine models. RESULTS/ANTICIPATED RESULTS: We anticipate that the proposed studies in Aim 1 will demonstrate reduction in the interaction of platelets with leukocytes results in exacerbation of kidney injury upon CKD induction with cisplatin. We also anticipate that inhibition of platelets in Aim 2 with P2Y12 receptor inhibitors results in reduction in kidney injury upon CKD induction with cisplatin. DISCUSSION/SIGNIFICANCE: Upon successful completion of the proposed studies, we shall be able to better describe the role of platelets as modulators of inflammation in CKD. This will be a significant stride towards understanding the pathophysiology of a pro-inflammatory state in CKD and how platelets exacerbate inflammation and thrombosis in this population.