Contributions to nephrology
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Fluid management in critically ill patients is a complex process as aggressive fluid resuscitation is commonly utilized for initial hemodynamic support and fluid administration often contributes to fluid retention, particularly when there is impaired kidney function. Recent evidence suggests that fluid accumulation is associated with adverse outcomes. It is unclear whether fluid retention is simply a marker of the severity of organ failure or a mediator of events. In this article we review the evidence and provide a framework for future studies to refine these concepts further.
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Endothelial cells play a key role in initiating and propagating the inflammatory response seen in ischemia, infections and sepsis. Situated in a key position between the epithelial cells and white blood cells (WBC), they interact and respond to signals from both cell types. ⋯ This last event is in large part responsible for a chronic reduction in regional perfusion, subsequent increased vulnerability to recurrent acute kidney injury, and acceleration of chronic kidney disease progression to end-stage renal disease. Glomerular endothelial dysfunction may lead to preglomerular shunting of blood flow allowing kidney blood flow to remain close to normal while resulting in a reduction in glomerular filtration rate.
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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) can no longer be considered a surrogate marker for severity of illness. Recent epidemiologic data demonstrate the association of AKI and mortality. Even small decreases of kidney function are associated with increased mortality. ⋯ Infection and antimicrobial therapy can be the cause of AKI, but infection can also be a consequence of AKI. Finally, inadequate antimicrobial dosing probably plays an important role in the morbidity and mortality of AKI. These findings have led to a paradigm shift: patients die because of AKI rather than with AKI.
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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.