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Clinical impact of enhanced cytokine clearance with sustained high-efficiency daily diafiltration using a mediator-adsorbing membrane (SHEDD-fA) in patients with severe sepsis


SHEDD-fA is an effective modality that makes the best use of three principles in the treatment of severe sepsis: diffusion, convection and adsorption. We reported the efficacy of SHEDD-fA for the treatment of severe sepsis at the 31st ISICEM 2011 [1]. Here we present the blood clearance (CL) of seven important cytokines with SHEDD-fA.


Ten critically ill patients were studied who were on SHEDD-fA, at QB = 150 ml/minute, QF = 1,500 ml/hour (post dilution) and QD = 300 to 500 ml/minute as a nonrenal indication. In order to maximize cytokine adsorption efficiency, we used a large-size (2.1 m2) PMMA dialyzer. Blood samples were taken to measure the CL of plasma cytokines (HMGB-1, IL-6, IL-8, IL-10, G-CSF, MCP-1 and MIP-1) at 1 hour and 3 hours after initiation (in one cytokine by 62 to 107 samples).


The median values of CL with interquartile ranges of each cytokine (molecular weight: kDa) were: HMGB1 (30 kDa), 53.1 ml/minute (2.1 to 12.5); IL-6 (21 kDa), 39.9 ml/minute (12.4 to 70.6); IL-8 (8 kDa), 64.1 ml/minute (-0.5 to 82.0); IL-10 ml/minute (35 to 40 kDa), 45.6 ml/minute (0.5 to 88.3); G-CSF (19 kDa), 33.2 ml/minute (9.3 to 60.8); MCP-1 (8.7 kDa), 68.5 ml/minute (-14.4 to 125.4); and MIP-1 (7.8 kDa), 66.5 ml/minute (18.6 to 100.0). In particular, CL of HMGB1 was positively correlated with pre-SHEDD-fA blood levels, indicating the mechanism of HMGB1 removal was through adsorption. As a result of enhancing the intensity of the dosage, CL (53 ml/minute) of HMGB1 was higher than that (25 ml/minute) of an in vitro experiment that we reported at the 31st ISICEM 2011. See Figure 1.

Figure 1
figure 1

Correlation between clearance and blood level of cytokines.


Taking into account the fact that the creatinine CL of native kidney function is 100 ml/minute, our findings suggest that SHEDD-fA is a feasible adjusted modality for the treatment of patients with severe sepsis, with or without acute kidney injury. Considering our other laboratory findings, deep filtration may enhance blood clearance.


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    Nishida O, et al.: Contrib Nephrol. 2011, 173: 172-181.

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Correspondence to O Nishida.

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Nishida, O., Nakamura, T., Kuriyama, N. et al. Clinical impact of enhanced cytokine clearance with sustained high-efficiency daily diafiltration using a mediator-adsorbing membrane (SHEDD-fA) in patients with severe sepsis. Crit Care 16, P383 (2012).

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  • PMMA
  • Severe Sepsis
  • Kidney Function
  • Acute Kidney Injury
  • Clinical Impact