ABSTRACT
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.
Subject(s)
Acrylic Resins/chemistry , Acrylonitrile/analogs & derivatives , Acute Disease/therapy , Fibroblast Growth Factors/blood , Hemodiafiltration/instrumentation , Membranes, Artificial , Acrylonitrile/chemistry , Adsorption , Aged , Biomarkers/blood , Down-Regulation , Equipment Design , Female , Fibroblast Growth Factor-23 , Humans , Male , Middle Aged , Protein Binding , Surface Properties , Time Factors , Treatment OutcomeABSTRACT
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.
