Contributions to nephrology
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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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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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Sustained high-efficiency daily diafiltration using a mediator-adsorbing membrane (SHEDD-fA) is an effective, intensive modality for sepsis treatment. Here we describe the effectiveness of SHEDD-fA, which makes the best use of three principles: dialysis, filtration and adsorption, for mediator removal in the treatment of severe sepsis. SHEDD-fA was initiated after adequate fluid resuscitation and catecholamine support had been provided. ⋯ Because SHEDD-fA is an intensive and high-efficiency modality, removal of useful drugs or nutrients may be observed. Despite the fact that removal of useful substances cannot be ignored, we believe that an appropriate stage or timing can be identified so that we can avoid a vicious cycle and use blood purification with effective diffusion, filtration and adsorption. We demonstrate that SHEDD-fA may be an effective, intensive modality for the treatment of patients with severe sepsis and is a possible modality for cytokine modulation therapy.
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Since 1994, a polystyrene fiber cartridge used for extracorporeal hemoperfusion, to which polymyxin B is bound and immobilized, has been used in septic patients in order to absorb and remove circulating lipopolysaccharide, thereby neutralizing the effects of this endotoxin. This therapy gradually gained acceptance as the amount of evidence increased from initial small clinical studies to a carefully conducted systematic review, and ultimately to the multicentered randomized clinical trial conducted in Italy, entitled the EUPHAS Study (Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock). While the conclusions of this initial randomized controlled trial were in agreement with previous studies, it possessed some important limitations, including a slow accrual rate, enrolling only 64 patients between 2004 and 2007, inability to blind treating physicians, and a premature study termination based on the results of the scheduled interim analysis. ⋯ In response, Italian investigators and users of this treatment have designed a new prospective multicentered, collaborative data collection study, entitled EUPHAS 2. The aim of the EUPHAS 2 project is to collect a large database regarding polymyxin B-hemoperfusion treatments in order to better evaluate the efficacy and biological significance of endotoxin removal in clinical practice. Additionally, this study aims to verify the reproducibility of the data currently available in the literature, evaluate the patient population chosen for treatment and identify subpopulations of patients who may benefit from this treatment more than others.
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The extracorporeal carbon dioxide removal (ECCO(2)R) concept, used as an integrated tool with conventional ventilation, plays a role in adjusting respiratory acidosis consequent to tidal volume (Vt) reduction in a protective ventilation setting. This concept arises from the extracorporeal membrane oxygenation (ECMO) experience. Kolobow and Gattinoni were the first to introduce extracorporeal support, with the intent to separate carbon dioxide removal from oxygen uptake; they hypothesized that to allow the lung to 'rest' oxygenation via mechanical ventilation could be dissociated from decarboxylation via extracorporeal carbon dioxide removal. ⋯ The future development of more and more efficient devices capable of removing a substantial amount of carbon dioxide production (30-100%) with blood flows of 250-500 ml/min is foreseeable. Moreover, in the future ARDS management should include a minimally invasive ECCO(2)R circuit associated with noninvasive ventilation. This would embody the modern mechanical ventilation philosophy: avoid tracheal tubes; minimize sedation, and prevent ventilator-induced acute lung injury and nosocomial infections.