Contributions to nephrology
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Acute kidney injury (AKI) is a serious condition that affects many intensive care unit (ICU) patients. The most common causes of AKI in the ICU are severe sepsis and septic shock. The mortality of AKI in septic critically ill patients remains high despite our increasing ability to support vital organs. ⋯ It would seem logical, therefore, to focus on the glomerulus in trying to understand why such loss of GFR occurs. Recent experimental observations suggest that, at least in the initial phases of septic AKI, profound changes occur which involve glomerular hemodynamics and lead to loss of GFR. These observations imply that changes in the vasoconstrictor tone of both the afferent and efferent arterioles are an important component of the pathogenesis of septic AKI.
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Despite the identification of several of the cellular mechanisms thought to underlie the development of acute kidney injury (AKI), the pathophysiology of AKI is still poorly understood. It is clear, however, that instead of a single mechanism being responsible for its etiology, AKI is associated with an entire orchestra of failing cellular mechanisms. Renal microcirculation is the physiological compartment where these mechanisms come together and exert their integrated deleterious action. ⋯ Under pathological conditions, such as inflammation, shock or sepsis, however, the renal microcirculation becomes compromised, which results in a disruption of the homeostasis of nitric oxide, reactive oxygen species, and oxygen supply and utilization. This imbalance results in these compounds exerting pathogenic effects, such as hypoxemia and oxidative stress, resulting in further deterioration of renal microcirculatory function. Our hypothesis is that this sequence of events underlies the development of AKI and that integrated therapeutic modalities targeting these pathogenic mechanisms will be effective therapeutic strategies in the clinical environment.
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Acute kidney injury (AKI) remains a major clinical challenge, especially in combination with acute lung injury (ALI). Clinical as well as experimental studies have provided evidence for clinically relevant kidney-lung interactions, ultimately leading to a drastic reduction in survival. The crosstalk between AKI and ALI is a consequence of both direct loss of normal organ function and inflammatory dysregulation resulting from each organ failure. ⋯ Lung protective ventilation, including low tidal volume ventilation, is a cornerstone in the management of ALI. This approach has been shown to attenuate both the direct mechanical effects of ventilation and the inflammatory response arising from ALI and mechanical ventilation, ultimately reducing the incidence of extrapulmonary organ failure. The fact that multiorgan failure is not only the sum of organ functions lost, but also includes inflammatory dysregulation together with a lack of treatment options greatly emphasizes the need for future research in this area.
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Sepsis-induced acute kidney injury (AKI) is the most common form of AKI observed in critically ill patients. AKI mortality in septic critically ill patients remains high despite our increasing ability to support vital organ systems. This high mortality is partly due to our poor understanding of the pathophysiological mechanisms of sepsis-induced AKI. ⋯ Sepsis-induced renal microvascular alterations (vasoconstriction, capillary leak syndrome with tissue edema, leukocytes and platelet adhesion with endothelial dysfunction and/or microthrombosis) and/or an increase in intra-abdominal pressure could contribute to an increase in RVR. Further studies are needed to explore the time course of renal microvascular alterations during sepsis as well as the initiation and development of AKI. Doppler ultrasonography combined with the calculation of the resistive indices may indicate the extent of the vascular resistance changes and may help predict persistent AKI and determine the optimal systemic hemodynamics required for renal perfusion.
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The modern definition and classification of acute kidney injury (AKI) has now been applied to thousands of patients around the world and in different settings. Epidemiology is shedding intense light on the credibility of our fundamental notions of how AKI occurs and why. It is clear from multiple studies that sepsis is the leading etiology of AKI, although other settings associated with systemic inflammation (polytrauma, burns, pancreatitis, cardiopulmonary bypass) also represent important means of exposure. ⋯ Dissonance of mediator secretion and cell responses may lead to persistent injury and de novo chronic kidney disease. A number of soluble mediators initiate a variety of pathophysiological processes as kidney injury evolves. In this chapter, we will discuss the pathogenesis of AKI in light of new information concerning injury and repair, and focus on the controversies arising from emerging evidence.