A reconsideration of effective mediator removal based on hemofiltration principles

Taking the HMGB1, notable alarmin, removal by hemofiltration for instance

Abstract

Cytokines play a pivotal role in severe sepsis and can lead to the development of tissue damage, metabolic acidosis, hypotension and even death. Uuseful convective removal for mediators from the human circulation has not been achieved to date, although many cytokines have a molecular weight of 20-30kD which is below the theoretical cut-off point of the commercial membranes currently used. On the other hand, adsorption has been identified as a major mechanism for cytokine removal both in vitro and in vivo；nevertheless the membranes used are not specifically designed. Recently new high cut-off membranes or new adsorbing-membranes have developed for septic acute kidney injury；however, there is no clinical-protocol design of taking the choice of the membrane into account. The ability of HMGB1 adsorption for AN69ST was extremely high according to the report of the HMGB1 removal by Dr. Yumoto et al. The removal of the substance such as HMGB1 which is very well adsorbed to the AN69ST membrane could be maximized to blood flow rate when using adsorption membrane, but when using high cut-off membrane the removal would be limited within the filtration flow rate. As to adsorption mechanism, there is the report that the adsorption reaches saturation in a short time outside Japan. However, a quantity of adsorption or adsorption time will depends on the degree of fitting the mediator to membrane together well. In this review, we reconsidered the effective removal of the causative mediators based on the principle of the hemofiltration taking the in vitro experiment for the removal of HMGB1 as an example.