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During hyperinflammatory conditions that can occur in acute critical illness, such as shock or hypoperfusion, inflammatory mediators activate the endothelium, fueling a proinflammatory host-response as well as procoagulant processes. These changes result in shedding of the glycocalyx, endothelial hyperpermeability, edema formation, and lead to disturbed microcirculatory perfusion and organ failure. Different fluid strategies that are used in shock may have differential effects on endothelial integrity. Collectively, low protein content fluids seem to have negative effects on the endothelial glycocalyx, aggravating endothelial hyperpermeability, whereas fluids containing albumin or plasma proteins may be superior to normal saline in protecting the glycocalyx and endothelial barrier function. Targeting the endothelium may be a therapeutic strategy to limit organ failure, which hitherto has not received much attention. Treatment targets aimed at restoring the endothelium should focus on maintaining glycocalyx function and/or targeting coagulation pathways or specific endothelial receptors. Potential treatments could be supplementing glycocalyx constituents or inhibiting glycocalyx breakdown. In this review, we summarize mechanisms of endothelial dysfunction during acute critical illness, such as the systemic inflammatory response, shedding of the glycocalyx, endothelial activation, and activation of coagulation. In addition, this review focuses on the effects of different fluid strategies on endothelial permeability. Also, potential mechanisms for treatment options to reduce endothelial hyperpermeability with ensuing organ failure are evaluated. Future research is needed to elucidate these pathways and to translate these data to the first human safety and feasibility trials.The immune system is an evolutionary hallmark of higher organisms that defends the host against invading pathogens and exogenous infections. This defense includes the recruitment of immune cells to the site of infection and the initiation of an inflammatory response to contain and eliminate pathogens. However, an inflammatory response may also be triggered by noninfectious stimuli such as major surgery, and, in case of an overshooting, still not comprehensively understood reaction, lead to tissue destruction and organ dysfunction. Unfortunately, in some cases, the immune system may not effectively distinguish between stimuli elicited by major surgery, which ideally should only require a modest inflammatory response, and those elicited by trauma or pathogenic infection. Surgical procedures thus represent a potential trigger for systemic inflammation that causes the secretion of proinflammatory cytokines, endothelial dysfunction, glycocalyx damage, activation of neutrophils, and ultimately tissue and multisystem organ destruction. In this review, we discuss and summarize currently available mechanistic knowledge on surgery-associated systemic inflammation, demarcation toward other inflammatory complications, and possible therapeutic options. These options depend on uncovering the underlying mechanisms and could include pharmacologic agents, remote ischemic preconditioning protocols, cytokine blockade or clearance, and optimization of surgical procedures, anesthetic regimens, and perioperative inflammatory diagnostic assessment. Currently, a large gap between basic science and clinically confirmed data exists due to a limited evidence base of translational studies. We thus summarize important steps toward the understanding of the precise time- and space-regulated processes in systemic perioperative inflammation.In the perioperative setting, acute kidney injury (AKI) is a frequent complication, and AKI itself is associated with adverse outcomes such as higher risk of chronic kidney disease and mortality. Various risk factors are associated with perioperative AKI, and identifying them is crucial to early interventions addressing modifiable risk and increasing monitoring for nonmodifiable risk. Different mechanisms are involved in the development of postoperative AKI, frequently picturing a multifactorial etiology. For these reasons, no single renoprotective strategy will be effective for all surgical patients, and efforts have been attempted to prevent kidney injury in different ways. Epigenetics inhibitor Some renoprotective strategies and treatments have proven to be useful, some are no longer recommended because they are ineffective or even harmful, and some strategies are still under investigation to identify the best timing, setting, and patients for whom they could be beneficial. With this review, we aim to provide an overview of recent findings from studies examining epidemiology, risk factors, and mechanisms of perioperative AKI, as well as different renoprotective strategies and treatments presented in the literature.Acute kidney injury (AKI) remains a common complication in the perioperative setting affecting patients’ short- and long-term outcome. Because therapeutic options are restricted to the use of renal replacement therapy, preventive strategies have become increasingly important. Several substances have been investigated for preventing AKI with limited to no effects. The lacking effectiveness of all these therapies might be caused by the fact that the therapy was started too late. In all the studies, therapy was initiated once a reduced kidney function occurred. In contrast to the classical functional biomarkers, new renal biomarkers allow to identify kidney damage without a loss of function thus enabling the implementation of preventive measures at the stage of renal stress. The most promising preventive strategy to date seems to implement a bundle of supportive measures in patients at high risk for AKI as recommended by the Kidney Disease Improving Global Outcomes (KDIGO) group. This strategy includes the avoidance of nephrotoxic drugs and contrast agents, avoidance of hyperglycemia, optimization of perfusion pressure and hemodynamics with consideration of a functional hemodynamic monitoring, and close monitoring of renal function in patients at high risk for AKI. This review discusses new renal biomarkers for identifying kidney damage, the background of why the different measures of the KDIGO bundle might positively affect renal function and prevent the development of AKI, and presents the current literature of biomarker-based approaches in AKI.