Contributions to nephrology
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Endotoxin removal by polymyxin B immobilized cartridge inactivates circulating proapoptotic factors.
Severe sepsis and septic shock continue to be major clinical challenges due to high associated mortality. Lipopolysaccharide (LPS) is a component of the cell membrane of Gram-negative bacteria, and is believed to initiate septic-induced signaling, inflammation and organ damage, including acute renal failure. Polymyxin B (PMX-B) hemoperfusion of septic patients can improve survival and decreasing organ dysfunction by removing circulating LPS. Unfortunately, some clinicians have been slow to adopt this novel therapy due to the lack of understanding of the cellular mechanisms involved in this treatment. Apoptosis, or programmed cell death, is known to contribute to acute renal failure and overall organ dysfunction during sepsis, and can be activated by LPS-initiated signaling pathways. Therefore, the protective renal effects associated with PMX-B hemoperfusion of septic patients may result from alterations in cellular apoptosis. This chapter will review recent data regarding the role of apoptosis prevention in the mechanism leading to the improved outcome and decreased acute renal failure associated with PMX-B hemoperfusion during sepsis. ⋯ The protective effects of extracorporeal therapy with PMX-B on the development of acute renal failure result, in part, through its ability to reduce the systemic proapoptotic activity of septic patients on renal cells.
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Multicenter Study Clinical Trial
Plasma dia-filtration for severe sepsis.
The mortality rate in severe sepsis is 30-50%, and independent liver and renal dysfunction impacts significantly on hospital and intensive care mortality. If 4 or more organs fail, mortality is > 90%. Recently, we reported a novel plasmapheresis--plasma diafiltration (PDF)--the concept of which is plasma filtration with dialysis. ⋯ On average, 12.0 +/- 16.4 sessions (range 2-70) per patient were performed. The 28-day mortality rate was 36.4%, while the predicted death rate was 68.0 +/- 17.7%. These findings suggest that PDF is a simple modality and may become a useful strategy for treatment of patients with septic multiple organ failure.
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Continuous renal replacement therapy (CRRT) has been extensively used in Japan as renal support for critically ill patients managed in the ICU. In Japan, active research has also been conducted on non-renal indications for CRRT, i.e. the use of CRRT for purposes other than renal support. Various methods of blood purification have been attempted to remove inflammatory mediators, such as cytokines, in patients with severe sepsis or septic shock. ⋯ In evaluating the efficacy of CRRT for non-renal indications, it is essential to focus on patients subjected to be studied, such as severe sepsis or septic shock, and to evaluate its indication, commencement, termination of therapy and also its therapeutic effects based on analysis of blood levels of the target substances to be removed (e.g. cytokines). IL-6 blood level appears to be useful as a variable for this evaluation. It is expected that evidence endorsing the validity of these methods now being attempted in Japan will be reported near future.
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Polymyxin B fiber column is a medical device designed to reduce blood endotoxin levels in sepsis. Gram-negative-induced abdominal sepsis is likely to be associated with high circulating endotoxin. In June 2009, the EUPHAS study (Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis) was published in JAMA. ⋯ The PaO(2)/FiO(2) ratio increased slightly (235 to 264; p = 0.049) in the polymyxin B group, but not in the conventional therapy group (217 to 228; p = 0.79). SOFA scores improved in the polymyxin B group, but not in the conventional therapy group (change in SOFA: -3.4 vs. -0.1; p = 0.001), and 28-day mortality was 32% (11/34 patients) in the polymyxin B group and 53% (16/30 patients) in the conventional therapy group (unadjusted HR: 0.43, 95% CI: 0.20-0.94; adjusted HR: 0.36, 95% CI:0.16-0.80). The study demonstrated how polymyxin B hemoperfusion added to conventional therapy significantly improved hemodynamics and organ dysfunction and reduced 28-day mortality in a targeted population with severe sepsis and/or septic shock from intra-abdominal Gram-negative infections.
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Fluid overload may occur in patients with heart failure. Further complications may arise when cardiorenal syndromes develop and the kidneys are unable to eliminate the accumulated fluid. Diuretics represent the fist line of treatment, although in some case they may be ineffective or even dangerous for the patient. ⋯ Then, an evaluation of biomarkers of heart failure and a careful analysis of body fluid composition by bioimpedance vector analysis should be carried out to establish the level of hydration and to guide fluid removal strategies. Last but not least, an adequate extracorporeal technique should be employed to remove excess fluid. Preference should be given to continuous forms of ultrafiltration (slow continuous ultrafiltration, continuous venovenous hemofiltration); these techniques guided by a continuous monitoring of circulating blood volume allow for an adequate restoration of body fluid composition minimizing hemodynamic complications and worsening of renal function especially during episodes of acute decompensated heart failure.