The role of platelets in acute kidney injury

Acute kidney injury (AKI) has emerged as a major public health problem, caused by a broad range of etiologies, of which systemic inflammation-induced AKI and ischemia reperfusion (I/R) induced AKI, account for the greater part of AKI cases in hospital setting. Both I/R and systemic inflammation result in renal macro- and microcirculation alterations leading to hypoxemic insults, resulting in an up regulation of inflammation and haemostatic processes. For still not completely understood reasons inflammation and hemostasis often tip towards an exaggerated and poorly controlled response, causing decreased renal blood flow, sustained hypoxia and subsequently increased irreversible renal tissue damage.
Platelets are recognized as important first responding actors in the development of acute inflammatory and hemostatic processes, and therefore form interesting targets to control the inflammatory and hemodynamic output in AKI. The aim of the research described in this dissertation, was to study the involvement of platelets in acute renal disease. Although we could not find solid evidence for platelets as a causative factor in human AKI, the work in this dissertation does provide evidence of intra-renal platelet activation upon renal I/R injury in mice. Most importantly, we reveal a close interaction between intra-renal platelet activation, necrotic cells, release of mitochondrial DNA and intra-renal neutrophil extracellular trap formation upon renal I/R, which together may form a potentially targetable driving force in AKI.