Contributions to nephrology
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Several large observational studies or randomized controlled trials in the field of critical care nephrology have been completed and reported, or recently completed or have recently begun recruitment. These studies provide important information to guide our appreciation of current practice and consider new potentially effective intervention for the prevention or attenuation of acute kidney injury or suggest new avenues for the use of renal replacement therapy (RRT) in the treatment of sepsis. In particular, two studies, the ATN study and the RENAL study (both multicenter randomized controlled trials of > 1,000 patients) provide, for the first time, level I evidence to guide the practice of RRT in critically ill patients and to better define the optimal intensity of such RRT in this setting. Clinicians practicing in the field of critical care nephrology need to be aware of these trials, their details, their findings or design or current recruitment rate and likely time of completion to continue to offer their patients the highest level of evidence-based medical care.
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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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Review Case Reports
Diuretic therapy in fluid-overloaded and heart failure patients.
Diuretics are the most commonly used drugs to treat clinically diagnosed fluid overload in patients with heart failure. There is no conclusive evidence that they alter major outcomes such as survival to hospital discharge or time in hospital compared to other therapies. However, they demonstrably achieve fluid removal in the majority of patients, restore dry body weight, improve the breathlessness of pulmonary edema and are unlikely to be subjected to a large double-blind randomized controlled trial in this setting because of lack of equipoise. ⋯ Such therapy often requires more intensive monitoring than available in medical wards. If diuretic therapy fails to achieve its clinical goals, ultrafiltration by semipermeable membranes is reliably effective in achieving targeted fluid removal. The combination of diuretic therapy and/or ultrafiltration can achieve volume control in essentially all patients with heart failure.
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Blood purification in critical care can perform 2 main functions: as an artificial support for failing organs (such as artificial kidney or liver support) and as a remover of causative humoral mediators of critical illness (such as severe sepsis and acute respiratory distress syndrome). As an artificial kidney, continuous blood purification (such as continuous hemofiltration and continuous hemodiafiltration, CHDF) is widely applied in intensive care units. The intensity of renal replacement therapy, however, has been reported to have no impact upon the efficacy of the blood purification in terms of clinical outcome. ⋯ However, our understanding of the pathophysiology of sepsis has changed since the concept of pattern recognition receptors and pathogen-associated molecular patterns was introduced. According to this, CHDF with a cytokine-adsorbing polymethylmethacrylate membrane hemofilter is preferable and more effective than direct hemoperfusion with an endotoxin-adsorbing polymyxin-B immobilized column in the treatment of sepsis and septic shock. Blood purification in critical care is gaining popularity, and is widely for both renal and non-renal indications.
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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.