In view of the above considerations, the ECF/ICF ratio measured by MF-BIA may be highly related to the MIA complex, and could be defined as a novel integrated marker reflecting both fluid overload and malnutrition ( Fig 1). At high frequencies, currents flow across both intra- and extracellular spaces however, at low frequencies, currents flow mainly through extracellular space allowing the assessment of ECF, ICF, and TBF. It is possible to distinguish between total body fluid (TBF) and ECF with multi-frequency bioimpedance analysis (MF-BIA), by using the resistance of cell membranes to relatively low-frequency currents. In addition, malnutrition caused by inflammation could deplete body cell mass, which eventually leads to the decrease in intracellular fluid (ICF) volume, and the relative increase in ECF/ICF volume ratio. Conversely, hypoalbuminemia and increased vascular permeability caused by inflammation will enhance extravascular fluid shift, resulting in ECF volume overload. Fluid overload might also play an important role in the development of arteriosclerosis, through the increase in vessel wall stress caused by arterial distension (Laplace’s law). It has been proposed that fluid overload act as an inflammatory stimulus by immune activation resulting from poor tissue perfusion, and bowel edema- induced translocation of bowel endotoxins into the circulation. There are also several supporting data showing the causal relationships between extracellular fluid (ECF) overload and the MIA complex. Among the MIA components, inflammation seems to play a pivotal role in the pathogenesis of malnutrition and arteriosclerosis by the following mechanisms: (1) inflammatory response is responsible for malnutrition by increased protein catabolism and muscle wasting and (2) uremic inflammation is known to promote extra-osseous deposition of calcium to vessel walls, resulting in vascular calcification and arteriosclerosis. Recently, a strong association between malnutrition, inflammation, and arteriosclerosis/atherosclerosis (the so-called MIA syndrome) have been described and proposed as the main causes of morbidity and mortality in chronic hemodialysis patients. For a long time, fluid overload and malnutrition have been known to be major risk factors for morbidity and mortality in chronic hemodialysis patients.
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