Contributions to nephrology
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Clinical Trial
Continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter for severe acute pancreatitis.
It has been reported that hypercytokinemia plays a pivotal role in the pathophysiology of severe acute pancreatitis (SAP). In our previous reports, continuous hemodiafiltration (CHDF) using a polymethyl methacrylate (PMMA) membrane hemofilter (PMMA-CHDF) was found to be capable of efficiently removing various cytokines from circulating blood. The present study was undertaken to evaluate the efficacy of PMMA-CHDF aimed at cytokine removal in the treatment of SAP. ⋯ At the time of weaning from PMMA-CHDF, blood IL-6 level had decreased to 99 pg/ml. The mortality rate among patients who received PMMA-CHDF was 6.1%, and significantly lower than that of patients before the introduction of PMMA-CHDF under non-renal indication (25.0%). These findings suggest that PMMA-CHDF is effective for treatment of SAP and that it can be expected to contribute to improving the outcome of SAP patients.
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Acute kidney injury (AKI) is a common complication among critical illnesses. In severe cases, renal replacement therapy (RRT) is required. It has been reported that hospital mortality of the patients who require RRT is more than 60%. ⋯ RRT practice is not aligned with the best evidence and variations in practice may be responsible for significant morbidity. The BEST Kidney Study has generated several hypotheses related to RRT practice in the intensive care unit. Such hypotheses will need to be tested in future clinical trials and hopefully help reduce practice variations for patients with AKI requiring RRT.
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Sepsis involves a complex interaction between bacterial toxins and the host immune system. Endotoxin, a component of the outer membrane of Gram-negative bacteria, is involved in the pathogenesis of sepsis producing proinflammatory cytokines and activating the complement system, and is thus an ideal potential therapeutic target. Direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-F) has been shown to bind and neutralize endotoxin in both in vitro and in vivo studies. ⋯ In this study, PMX-F, when added to conventional therapy, significantly improved hemodynamics and organ dysfunction, and reduced 28-day mortality in this targeted population. There is clear biological rationale for endotoxin removal in the clinical management of severe sepsis and septic shock. The current literature seems to provide some support for this premise, and provides the basis for further rigorous study.
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Endotoxin, which consists of lipopolysaccharide (LPS), is an outer membrane component of the Gram-negative bacterial cell wall. Endotoxin in the blood stream from an infectious focus or through translocation from the gut plays an important role in the pathogenesis of severe sepsis and septic shock. It binds to monocytes and macrophages, activating them to trigger the production of a variety of mediators. ⋯ In Japan, PMX has been clinically used since 1994under the national health insurance system. It is estimated that over 80,000 patients have received PMX treatment in Japan. Not only has PMX been clinically used safely in Japan, but also in other countries.
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Endotoxin activity (EA) plays an essential role in sepsis syndrome pathogenesis. There has been considerable interest in measuring and removing EA to predict and improve the morbidity and mortality of patients with sepsis. We performed a prospective study to assess the prevalence of EA in critically ill patients and its association with organ dysfunction and outcome, as well as in septic shock. ⋯ Our study demonstrated that EA level is independent from the type or the source of infection, but reflects the severity of illness in critically ill septic shock patients. Extracorporeal EA removal (PMX-HP) was assessed following our ICU clinical practice. PMX-HP seems to have better outcome, but further studies are required to verify this hypothesis.