The Japanese Society for Apheresis clinical practice guideline for therapeutic apheresis.

Most of the diseases for which apheresis therapy is indicated are intractable and rare, and each patient has a different background and treatment course prior to apheresis therapy initiation. Therefore, it is difficult to conduct large-scale randomized controlled trials to secure high-quality evidence. Under such circumstances, the American Society for Apheresis (ASFA) issued its guidelines in 2007, which were repeatedly revised until the latest edition in 2019. The ASFA guidelines are comprehensive. However, in the United States, a centrifugal separation method is mainly used for apheresis, whereas the mainstream procedure in Japan is the membrane separation method. The target diseases and their backgrounds are different from those in Japan. Due to these differences, the direct adoption of the ASFA guidelines in Japanese practice creates various problems. One of the features of apheresis in Japan is the development of treatment methods using hollow-fiber devices such as double filtration plasmapheresis (DFPP) and selective plasma exchange and adsorption-type devices such as polymyxin B-immobilized endotoxin adsorption columns. Specialists in emergency medicine, hematology, collagen diseases/rheumatology, respiratory medicine, cardiovascular medicine, gastroenterology, neurology, nephrology, and dermatology who are familiar with apheresis therapy gathered for this guideline, which covers 86 diseases. In addition, since apheresis therapy involves not only physicians but also clinical engineers, nurses, dieticians, and many other medical professionals, this guideline was prepared in the form of a worksheet so that it can be easily understood at the bedside. Moreover, to the clinical purposes, this guideline is designed to summarize apheresis therapy in Japan and to disseminate and further develop Japanese apheresis technology to the world. As diagnostic and therapeutic techniques are constantly advancing, the guidelines need to be revised every few years. In order to ensure the high quality of apheresis therapy in Japan, both the Japanese Society for Apheresis Registry and the guidelines will be inseparable.

The Superiority of AN69ST Membrane in the Adsorption of Fibroblast Growth Factor-23.

BACKGROUND: The most frequent cause of acute kidney injury (AKI) needing renal replacement therapy is sepsis, with the prognosis of patients with septic AKI worse than for other causes of this disease. Recent studies have shown that fibroblast growth factor-23 (FGF-23) levels, one of the phosphaturic and prognostic factors in chronic kidney disease, are also elevated in patients with AKI and correlate with an increased risk of death or a need for dialysis. In addition, FGF-23 was found to inhibit the extra-renal synthesis of 1,25-dihydroxyvitamin D by human monocytes. Therefore, the elevated expression of FGF-23 may play a crucial role in defining the immune response to vitamin D and this, in turn, may be a key determinant of infection in patients. Continuous renal replacement therapy (CRRT) is often essential for the treatment of septic AKI. However, reports related to the influence of CRRT on serum FGF-23 levels are lacking. In this study, we undertook preliminary in vitro investigations evaluating the effect of different types of CRRT membranes on FGF-23 adsorption. METHODS: To study how FGF-23 is adsorbed by hemofiltration fiber, in vitro experiments were performed based on a batch method using three types of fiber: polysulfone (PS), polymethyl methacrylate (PMMA), and acrylonitrileco-methallyl sulfonate surface treatment (AN69ST) fiber. RESULTS: The adsorptive properties of the various membranes were determined from measuring changes in the concentration of FGF-23 in a solution containing the membrane after incubation for 60 or 240 minutes. The amount of FGF-23 adsorbed by an AN69ST membrane was significantly more than for other membranes (P < 0.01). The amounts adsorbed by PS and PMMA membranes were similar. CONCLUSIONS: We found an AN69ST membrane has a greater capacity for FGF-23 adsorption than two other membranes tested. Although this is an in vitro study, we believe the present findings indicate an exciting new direction in the treatment of septic AKI and highlight the necessity of acute clinical investigations using AN69ST-CRRT.

Continuous Hemodiafiltration with an AN69ST Hemofilter (AN69ST-CHDF) as FGF-23-Lowering Therapy.

BACKGROUND: Recent studies have shown that fibroblast growth factor-23 (FGF-23) is elevated not only in chronic kidney disease (CKD), but also in acute illnesses such as acute kidney injury, septic shock, and acute heart failure. FGF-23 would be not only a simple biomarker but also a direct toxic factor in acute illness. Therefore, lowering circulating FGF-23 levels in clinical practice would be an exciting and valuable interventional strategy. Continuous hemodiafiltration (CHDF) is often performed for the treatment of the aforementioned acute illnesses. We have previously reported that an acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane has a greater capacity for in vitro FGF-23 adsorption than polysulfone and polymethyl methacrylate membranes. However, reports related to the influence of AN69ST-CHDF on serum FGF-23 levels in acute illness are lacking. In this study, we investigated the effect of AN69ST-CHDF on circulating FGF-23 concentrations in clinical practice. METHODS: Subjects comprised six inpatients who underwent AN69ST-CHDF for an acute illness. Blood samples for the measurement of serum FGF-23 were collected at 0, 3, and 12 hours post-treatment. Blood samples were also drawn from the extracorporeal circuit at the inlet and outlet of the hemofilter 3 hours after CHDF initiation, in order to calculate the clearance of serum FGF-23. RESULTS: Three and 12 hours after the start of AN69ST-CHDF, circulating FGF-23 levels decreased from baseline values with a marginal statistical significance (p = 0.0625 and 0.0938, respectively). An FGF-23 clearance of 27.5 [interquartile range: 19.4 - 29.2] mL/minute 3 hours after the initiation of AN69ST-CHDF was achieved. CONCLUSIONS: Our results suggest that AN69ST-CHDF can be a novel FGF-23 lowering therapy for acute illnesses requiring acute blood purification.

Effective combination therapy of polymyxin-B direct hemoperfusion and recombinant thrombomodulin for septic shock accompanied by disseminated intravascular coagulation: a historical controlled trial.

Disseminated intravascular coagulation (DIC) and multiple organ failure often occur via the crosstalk between inflammation and coagulation, which is mediated by High Mobility Group Box 1 (HMGB1). In septic shock, Polymyxin-B direct hemoperfusion (PMX-DHP) ameliorates hemodynamics by endogenous cannabinoid adsorption and improves pulmonary oxygenation by indirect cytokine reduction through the adsorption of activated mononuclear cells. However, PMX-DHP has no direct effect on HMGB1 circulating in the plasma. In cases with DIC, recombinant thrombomodulin (rTM), an effective drug for DIC, exerts not only anticoagulation but also antiinflammatory properties via direct anti-HMGB1 activity. Therefore, a combination of PMX-DHP and rTM is expected to block the vicious cycle of a cytokine storm ending up with multiple organ failure in DIC. The aim of this study was to investigate the efficacy of combination therapy for septic shock associated with DIC. This study comprised 22 consecutive patients with sepsis-induced DIC who received PMX-DHP. The initial eight patients were treated without rTM (historical control group), and the following 14 patients were given rTM (rTM group). The baseline Sequential Organ Failure Assessment (SOFA) score or age was not different between both groups. Sixty-day survival rate in the rTM group was significantly higher than that in the control group (85.7% vs. 37.5%, P = 0.015). A combination of PMX-DHP and rTM may be effective in septic shock accompanied by DIC and is expected to improve survival rates.