Contributions to nephrology
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All aspects of current treatment of acute kidney injury (AKI), including renal replacement therapy (RRT), are basically supportive. Emergent RRT is indicated in the management of AKI with refractory pulmonary edema, hyperkalemia or metabolic acidosis, or when uremic symptoms or signs develop. More aggressive practitioners use prophylactic RRT inpatients with sustained anuria, persistent oliguria with progressive azotemia and a probable glomerular filtration rate < 10 ml/min, or to prevent uncontrolled positive fluid balance in patients with AKI. ⋯ The approach to RRT dosing in AKI is more evidence-based. Outcomes in single-center studies of higher intensity versus standard RRT (intermittent and/or continuous) have been in consistent. However, two large multicenter negative randomized trials have shifted the weight of evidence towards suggesting provision of an effectively delivered standard dose of RRT in AKI, rather than seeking to increase RRT intensity.
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Review Comparative Study
Acute kidney injury, acute lung injury and septic shock: how does mortality compare?
Acute kidney injury (AKI), acute lung injury (ALI) and sepsis are all commonly encountered in critically ill patients. Although considered as separate conditions, largely for therapeutic purposes, a common inflammatory response is often implicated in their pathophysiologies and they are frequently present simultaneously. Mortality rates in critically ill patients suffering from renal failure, respiratory failure or severe sepsis are quite similar at about 40%, and all increase substantially when these conditions coexist. Most intensive care unit patients will die from multiple rather than individual organ failure, and further research is needed to evaluate the patterns of organ failure in surviving and nonsurviving critically ill patients, as well as the importance and mechanisms of organ-organ crosstalk in such patients.
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The pathogenesis of sepsis-induced acute kidney injury (AKI) is not fully understood, and may involve altered systemic hemodynamics and renal circulation, renal hypoxia and perhaps direct tubular toxicity. Oxidative stress, induced by systemic and intrarenal generation of reactive oxygen species (ROS) can directly exert renal parenchymal damage and may intensify renal microvascular and functional dysregulation, with a feedforward loop of hypoxia and ROS generation. Herein we review compelling evidence that sepsis is associated with systemic and intrarenal intense oxidative and nitrosative stress with a depletion of antioxidant capacity. ⋯ Though oxidative and nitrosative stress are likely to participate in the pathogenesis of sepsis-induced AKI, it is impossible to clearly identify their isolated independent role and renal-specific effect since there are complex interactions involved linking various affected organs, ROS generation with altered systemic hemodynamics, compromised microcirculation, hypoxia and distorted cellular function. Facing this complex disease entity, alleviation of oxidative stress single-handedly is unlikely to be effective in the prevention of sepsis-associated renal dysfunction. However, the addition of antioxidants to a comprehensive treatment strategy seems a reasonable approach.
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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.