English

Abstract

Introduction Platelets were first discovered in 1842, identified as ‘little globules’ or ‘granular masses’. Since then, our understanding of these small nonnucleated cells has massively increased, and over the years the humble platelet has been found to be a critical player in many physiological processes. Here, we explore the role of platelets in patients with renal diseases and examine their significance in outcomes. Conclusion It is clear that, far from being mere ‘particles in the blood’, platelets are remarkable and exciting cells that have highly evolved and intricate functions spanning far beyond just haemostasis, encompassing many other physiological processes. Introduction Far from the first somewhat tentative identification of platelets as distinct morphologic elements in the blood in the nineteenth century, we have now amassed much information about their structure and function1. They are non-nucleated fragments of megakaryocytes. As each megakaryocyte develops in the bone marrow under the control of thrombopoietin, it fragments yielding in excess of 1,000 platelets. In the absence of endothelial activation, platelets circulate in the blood for approximately 10 days before being cleared primarily by the spleen. Despite being simple cytoplasmic fragments, platelets have a remarkable structure, with various surface proteins involved in aggregation and adhesion and secretory granules releasing proteins involved in haemostasis, and the ability to alter their shape and size upon activation. Platelets are, of course, key players in the process of haemostasis and have long been credited as being fundamental to the formation of stable blood clots upon activation of the coagulation cascade and via their interaction with exposed subendothelial von Willebrand factor (vWF) in the microcirculation. Increasingly, however, they are recognised to have many additional functions and in particular are acknowledged as contributors to vascular inflammation and the development of atherosclerotic disease. They secrete mediators of inflammation (cytokines, chemokines, growth factors, adhesion molecules and coagulation factors) and interact with other cells (dendritic cells, leukocytes and progenitor cells) to promote their activation and recruitment to sites of inflammation2. The aim of this review is to discuss the role of platelets in the prognosis of renal disease. Discussion The authors have referenced some of their own studies in this review. These referenced studies have been conducted in accordance with the Declaration of Helsinki (1964), and the protocols of these studies have been approved by the relevant ethics committees related to the institution in which they were performed. All human subjects, in these referenced studies, gave informed consent to participate in these studies. Inflammation and cardiovascular disease Before examining the role of platelets in inflammation, it is important to remember that it has been long known that inflammation is involved in the development of atherosclerosis in the general population3,4. Atherosclerosis is now very much recognised as being a chronic inflammatory condition of the vessel wall, with the development of atherosclerotic lesions being shaped by immune responses and regulations5 and the haemostatic system acting as a moderator6. Elevated levels of hs-CRP and plasma proinflammatory cytokines, in particular the IL-1 and IL-6 pathways, have been repeatedly implicated in atherogenesis7. Equally, patients with chronic kidney disease (CKD) are well recognised to be in a proinflammatory state8 with evidence that CRP, IL1, 6 and TNFa are elevated alongside ICAM-1 and VCAM-1 and act as predictors of cardiovascular death9. Platelets in inflammation Platelets have been identified as being effector cells that enhance inflammatory responses, with the ability to ‘cross-talk’ with endothelial cells and leukocytes10. When activated, they release over 300 proteins and molecules—some (including chemokines, angiogenic factors, ADP/ATP, coagulation factors) preformed and stored in dense bodies or alpha-granules, others (thromboxane, reactive oxygen species, IL-1b) synthesised upon stimulation11. In addition to secreting these various biologically active factors, activated platelets have also been shown to shed membrane microparticles (MPs)12. MPs are phospholipidand protein-rich submicron particles 0.1–2 mm in size. They shed from the membranes of several cell types when they are injured, activated or undergoing apoptosis in response to * Corresponding author Email: Suzanne.Forbes@bartshealth.nhs.uk Department of Nephrology and Transplantation, Royal London Hospital, Barts Health NHS Trust, Whitechapel, E1 1BB