Current drug targets
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Current drug targets · Dec 2009
ReviewNovel therapeutic targets for prevention and therapy of sepsis associated acute kidney injury.
Sepsis associated Acute Kidney Injury (SA-AKI) is the leading cause of AKI in the hospital setting and its incidence is increasing. Although the exact pathophysiology and phenotype of SA-AKI are not known, it is widely accepted that SA-AKI has a multi-injury pathway. ⋯ Promising agents that are in development include toll-like receptor inhibition, IL-10 augmentation, modulators of the protein C pathway, and mesenchymal stem cell mediated therapeutics. The aim of this review is to review the pathophysiology of SA-AKI and the therapeutic interventions that are under development to treat this complex and morbid disease.
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Septic acute kidney injury (AKI) occurs between 15% and 20% of all intensive care unit admissions and its mortality ranges from 20% to 60%. The incidence and mortality of septic AKI has remained high throughout the last 10 years, whereas our understanding of septic AKI pathogenesis has remained limited. ⋯ Improvement of knowledge about this condition seems to be most important in order to find valid diagnostic exams to exactly identify septic AKI and effective therapies to treat it: both of them are currently lacking. Finally, new preventive strategies might be experimented in order to protect critically ill patients from septic AKI.
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Imaging of the kidneys can provide valuable information in the work up and management of acute kidney injury. Several different imaging modalities are used to gather information on anatomy of the kidney, to rule out obstruction, differentiate acute kidney injury (AKI) and chronic kidney disease and to obtain information on renal blood flow and GFR. ⋯ In this review the basics of ultrasonography are reviewed with an emphasis on findings in AKI. The new developments in different imaging modality and their potential uses in AKI are reviewed as well.
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Current drug targets · Sep 2009
ReviewUse of corticosteroids in critically ill septic patients : a review of mechanisms of adrenal insufficiency in sepsis and treatment.
Adrenal insufficiency has being reported with increased frequency in critical ill patients with sepsis and other inflammatory states. Its incidence varies widely depending on the criteria used to define it and the patient population studied. Increased glucocorticoid action is essential in the stress response to acute injury and even minor degrees of adrenal insufficiency can be fatal. ⋯ Whether exogenous corticosteroid support may be beneficial in critical illness is still matter of debate: most international guidelines recommend that the decision to treat patients with corticosteroids should be based on clinical criteria (low blood pressure poorly responsive to vasopressor despite adequate fluid resuscitation) rather than on tests of the hypothalamic-pituitary-adrenal axis alone. As regards specifically the role of steroids in the treatment of sepsis and septic shock, at present there are no strong evidence-based recommendations. More studies are needed to reach consensus about several issues: which is the best target population, whether a cosyntropin test should be used to guide treatment, whether fludrocortisones should be given along with hydrocortisone, and how long treatment should continue.
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Statins are widely prescribed cholesterol lowering agents that exert their effects by inhibiting 3-hydroxy-3methylglutaryl co-enzyme A reductase. With their modulatory effects on the atherogenic lipid profile, the role of statin therapy is expanding amidst the growing obesity epidemic. The cholesterol lowering effects of statin therapy remains central in the long term management of coronary artery disease and cerebrovascular disease. ⋯ Clinical research into plaque histology, vulnerable high risk plaques and plaque rupture has improved our insight into the pathophysiology of these acute vascular events. Non lipid lowering effects of statin, the so called pleitrophic effects, have become the focal point of investigation. This review discusses recent experimental and clinical evidence supporting the role of statin in perioperative medicine.