Ulcerative colitis and Crohn disease are chronic inflammatory disease with an intractable, recurrent course. The molecular mechanism of these diseases remain unknown. Leukocytapheresis (LCAP) and Granulocytapheresis (GCAP) have been found effective for the treatment of UC and CD. The mechanisms of these therapies are postulated to block recruitment of immune cells to inflamed mucosa and to urge restoration of epithelial cells.

Therapeutic apheresis may be applied as treatment for various diseases, in which evidence of its efficacy has been established by randomized controlled trials, or apheresis can remove the pathogenic substance. Among neuroimmunological diseases, myasthenia gravis, Guillain-Barré syndrome, chronic inflammatory demyelinating neuropathy, and multiple sclerosis are accepted as covered under insurance and are applicable diseases that can be treated with apheresis in Japan. Apheresis can be also performed for neuromyelitis optica and autoimmune encephalitis. The modalities of the apheresis used in treatment of neuroimmunological disease are plasma exchange, double filtration plasmapheresis and immnoadsorption plasmapheresis. These seem to be equally effective in each disease mentioned above, but there is as yet no clinical trial evidence about which modality is most suitable for each disease. The condition of a patient needing apheresis therapy in neuroimmunological diseases is often severe and serious, and if the opportunity is not availed, recovery often becomes difficult. Thus it is important to enforce apheresis therapy immediately when necessary, while performing an appropriate differential diagnosis.

Plasma exchange therapy has been found to be effective for anti-glomerular basement membrane (GBM) disease, antineutrophil cytoplasmic antibody-associated vasculitis (AAV), IgA vasculitis, and cryoglobulinemic vasculitis. The most common indications are life-threatening or organ function-threatening manifestations. For AAV, plasma exchange (PE) therapy is recommended for patients with either severe renal impairment or diffuse alveolar hemorrhage. The largest trial published to date is the MEPEX (Methylprednisolone versus Plasma Exchange) trial, which recruited individuals who had a serum creatinine level of ＞5.66mg/dL. PE therapy appeared to be of value in preventing end-stage renal disease at 12 months, but long-term follow-up revealed no statistically significant benefit for the PE group. The PEXIVAS (Plasma Exchange and Glucocorticoids for Treatment of ANCA-Associated Vasculitis) trial is a global factorial randomized controlled trial. Eligible patients had a severe manifestation defined as either renal involvement, with a documented estimated glomerular filtration rate of ＜50mL/min, or lung hemorrhage. In the Japanese insurance system, administration of plasma exchange therapy is allowed only for patients with rapidly progressive glomerulonephritis caused by anti-GBM disease. Two courses of PE, composed of seven times in 2 weeks, are permitted. Concerning IgA vasculitis and cryoglobulinemic vasculitis, no global guidelines have been established and no randomized controlled trial has been conducted to evaluate the efficacy of PE therapy. Case series and reports support the efficacy of PE therapy for refractory or severe cases.

In the intensive care unit, physicians have to direct a variety of therapeutic strategies, including acute blood purification, with a multidisciplinary team composed of nurses and clinical engineers. Physicians frequently have to lead several teams at once for a patient, as either an expert or a non-expert. The key to conducting a team smoothly is communication. TeamSTEPPS^® has shown that leadership, situation monitoring, mutual support, and communication compose the core framework and competencies. Although electronic health records can be considered beneficial communication tools, unexpected communication errors can arise as a result of excess patient information. To resolve these patient safety issues, continuous education programs for medical staff and up-to-date standard operating procedures could be helpful with WHO Patient Safety Curriculum Guide. Thus, the promotion of patient-centered communications among both multidisciplinary teams and professional associates is important to reduce human error in patients undergoing acute blood purification.

Kidney injury molecule 1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury, and its ectodomain is shed into the lumen. The usefulness of urinary KIM-1 for early diagnosis of acute kidney injury (AKI) especially in cardiac surgery patients has been demonstrated by systematic review and meta-analysis. However, its usefulness for predicting prognosis and AKI severity, and in patients with sepsis has not been elucidated. It has been shown that KIM-1 upregulation in the kidney, following an injury, has a critical role in kidney repair. Thus, KIM-1 is gaining attention as a novel therapeutic target of AKI. Recent reports reveal that KIM-1 levels in blood might reflect not only kidney injury, but also other organ injuries and/or disease prognosis. Therefore, further investigations about the origin of circulating KIM-1 and its role are required.

Acute kidney injury (AKI) is diagnosed by rising serum creatinine (Cr) level (increase rate) and decreasing urine volume. However, as the serum Cr level has a low sensitivity for glomerular filtration rate loss in early stages, biomarkers that diagnose AKI more specifically and earlier, as well as reflect the severity are expected. As a low molecular weight protein (molecular weight is 13.3kDa) which is produced in a constant amount from whole nucleated cells, Cystatin C (Cys-C) is expected to be a biomarker of AKI, since it begins to rise above the reduced renal function in early stages compared with Cr. The most usefulness of Cys-C is being compatible with automatic biochemical analyzer, and possibility to practically apply in clinic. AKI is affected by complex factors such as damaged parts of the kidney or time elapsed since the damage occurred. Thus, not only Cys-C but various combinations of biomarkers are required, and the establishment of new biomarkers is urgently needed.

【Aim】This study examined the IL-6 adsorption performance of sepXiris100^® over time when used in clinical practice from July, 2014. sepXiris100^® is a continuous renal replacement therapy (CRRT) membrane produced by the Baxter Corp. 【Methods】Eight participants took part in the study. CRRT therapy data were recorded if IL-6 clearance was more than 1,000pg/mL after the first 15min of therapy. IL-6 clearance was measured at 15min, 1h, 24h and 48h after the start of therapy. 【Results】Mean IL-6 clearance （mL/min） was 17.3±5.1 at 15min, 7.2±7.1 at 1h, 6.5±5.6 at 24h and 10.2±11.8 at 48h. 【Conclusion】At 1h after therapy started, there was a marked decrease in IL-6 clearance compared with the first 15min of therapy. This sharp decrease did not continue and adsorption seemed to level out within 24h and increased slightly at 48h.

Continuous hemofiltration (AN-CHF) using an AN69ST hemofilter often causes blood coagulation in the venous chamber. We have postulated that this is due to the adsorption of nafamostat mesilate (NM), although this remains to be investigated. In our ICU, only prefilter NM administration was previously employed, but, subsequently, pre- and post-filter NM administration were introduced. Sepsis patients who received AN-CHF were selected and compared retrospectively regarding the administration methods (Method A: prefilter administration of NM at 30mg/hr; Method AV：prefilter at 25mg/hr and postfilter at 5mg/hr). Considering time loss due to CHF exchange and the inconvenience of exchange off duty, we defined cases where AN-CHF was performed for more than 22 hours with a single filter as “target achievement.” As a result, no significant difference was noted in lifetimes (23.5 hours for Method A vs. 23.2 hours for Method AV, p＝0.60) or target achievement rates (85.1% for Method A vs. 78.9% for Method AV, p＝0.34). Sequential organ failure assessment scores (odds ratio: 0.997, p=0.0002) and Method AV (odds ratio: 0.216, p=0.011) were included as factors contributing to target achievement. In conclusion, the divided administration of NM prefilter at 25mg/hr and postfilter at 5mg/hr was not effective for circuit lifetime in this study.

We performed ultrafiltration experiments of albumin (Alb) in vitro using prototype dialyzers, including polyester polymer alloy (PEPA) membrane with the same permeability, surface area of 0.81m² and packing density of hollow fibers and with different design factors in order to clarify the mechanisms of Alb transport. Ratios of effective length (L) to the diameter of housing （D） （L/D） were 9.3 (long & slim: LS), 5.1 (normal: N) and 2.9 (short and thick: ST), respectively, and the inner diameters of hollow fiber (d) were 170, 210 and 245μm. Therefore there examined total of 3×3=9 models. The test solution was prepared with chemical Alb dissolved in aqueous phosphate buffer of pH=7.4. Ultrafiltration experiments were performed for 12 hours at 310K. The flow rate of the test solution was 100mL/min, and that of ultrafiltration was 10mL/min. The minimum amount of Alb leakage at 12 hours was 1.2g in LS with d=170μm and the maximum was 4.3g in ST with d=245μm. The amount of Alb leakage can be expressed as a function of the average wall shear rate of the test solution. Therefore, it may be possible to control the Alb leakage by changing the d and/or other design factors.

Hemodialysis patients have a worse prognosis than non-dialysis patients. In addition to sudden cardiac death, they are at an increased risk to many acute onset conditions. This retrospective study evaluated hemodialysis patients who received cardiopulmonary resuscitation at our hospital between April 1, 2011 and May 31, 2016. The percentage of patients at our hospital who require hemodialysis increased annually, and the risk of sudden death was more than a hundredfold greater than in patients who did not require hemodialysis. Of the 117 cases of sudden death at our hospital, 17 were hemodialysis patients and all the patients who received cardiopulmonary resuscitation were hemodialysis patients. Emergency hospital admission of hemodialysis patients was more frequent for acute onset conditions than admission for other reasons. The possibility of rehabilitation of hemodialysis patients requiring cardiopulmonary resuscitation is very low. Hemodialysis patients had a variety of admission diagnoses ; the most common were acute cardiovascular complications against a background of previous heart disease. For these reasons, cardiovascular monitoring, including electrocardiography and management of electrolytes, during and after hemodialysis is important for early detection and prevention of acute onset events.

The circuits used in CRRT are exchanged every 48 hours at our hospital. During this 48-hour period, circuit obstruction is sporadically observed in some cases. Therefore, the hemofilter lifetime, the rate of achieving 48-hour CRRT, the difference between the arterial and venous pressures in a circuit, and the reasons for circuit exchange were compared between two types of hemofilters differing in membrane material and size (a polysulfone [PS] membrane hemofilter and a large surface area polymethyl methacrylate [PMMA] membrane hemofilter). The results indicated that the rate of achieving 48-hour CRRT was significantly higher with PS (36.7%) than with PMMA (68.7%) (p=0.00064). Moreover, blood clot formation in the chambers of the blood circuits, not hemofilter clotting, accounted for half of all circuit exchanges. This suggested that clot formation in CRRT circuits is affected not only by the performance of hemofilters but also by the biocompatibility of the membrane materials. Furthermore, this study found that large surface area PMMA membrane hemofilters are superior to PS membrane hemofilters in terms of suitability for use in CRRT not only for patients with sepsis but also for all other cases.

To elucidate the fouling mechanism of hemofilters, an aqueous ultrafiltration experiment was conducted. The hemofilters tested were AEF-10 (polysulfone membrane; henceforth abbreviated AEF), CH-1.3W (polymethylmethacrylate membrane; abbreviated CHW), and FLX-10GW (polyester polymer alloy membrane；abbreviated FLX). The albumin concentration of the aqueous test solution was 0.4g/dL and 4.0g/dL, the test solution flow rate (Q_B)was 100mL/min, and the total filtrate flow rate (Q_Ft) was held constant at 50mL/min. Sieving coefficient (s.c.) values for AEF hemofilters were initially high and then decreased with time at both albumin concentrations, but s.c. values for CHW and FLX hemofilters decreased with time as the albumin concentration increased from 0.4g/dL to 4.0g/dL. In addition, the filtrate flow rates at the inlet (Q_Fi) and outlet (Q_Fo) of the test solution were estimated from the material balance formula. With AEF hemofilters, Q_Fi and Q_Fo values were almost the same regardless of the albumin concentration. With CHW hemofilters, Q_Fi was higher than Q_Fo when the albumin concentration was 0.4g/dL, and the difference increased at concentrations of 4.0g/dL. With FLX hemofilters, Q_Fi and Q_Fo were almost the same when the albumin concentration was 0.4g/dL, but Q_Fi was higher when the concentration was 4.0g/dL. Therefore, fouling may occur at different sites depending on the hemofilter used, likely due to varying physicochemical features of the hemofilters.

Hematogenous dissemination of Klebsiella pneumoniae from a liver abscess causes systemic infection due to potent toxicity. We report a case of systemic septic embolism caused by Klebsiella pneumoniae, which originated from a liver abscess in a patient with type 2 diabetes mellitus who recovered following intensive care. A 52-year-old woman with a history of type 2 diabetes mellitus was admitted to hospital because of a high fever and consciousness disorder, and was diagnosed with systemic septic infection (multiple liver abscesses, pulmonary embolisms, meningitis and pyelonephritis). At admission, disseminated intravascular coagulation and multiple organ failure was detected. Blood culture showed heavy growth of Klebsiella pneumoniae. The patient’s general condition steadily improved after antibiotic treatment with polymyxin B hemoperfusion (PMX-DHP) and continuous hemodiafiltration (CHDF) in the intensive care unit. However, growth of a lung cavity lesion caused acute respiratory failure, and artificial respiratory care was required. A percutaneous gastrostomy tube was also placed. The patient’s general condition improved after weaning from positive pressure ventilation. Finally, oral ingestion was possible, and she was transferred to a rehabilitation hospital. Blood purification therapy from an early stage of disease was useful for multiple organ failure.

An 18-year-old woman was admitted to an area hospital for abdominal pain, diarrhea, and fever, but her condition deteriorated, and she was transported to our hospital. The patient also had melena, hematuria, hemolytic anemia, thrombopenia, and an enterohemorrhagic Escherichia coli O157 infection. The diagnosis was hemolytic uremic syndrome （HUS）, and treatment centering on supportive therapy was initiated. Acute kidney injury developed on the 4th day in the hospital, and continuous blood purification therapy was introduced. On the 7^th day in the hospital, the patient developed visual and auditory hallucinations, for which steroid semi-pulse therapy and plasma exchange were administered for 2 consecutive days. The hallucinations stopped, and her general condition rapidly improved. Continuous blood purification therapy was withdrawn on the 12th day in the hospital, and the patient was discharged with no renal or neurological sequela on the 25^th day in the hospital. Shiga toxin and inflammatory cytokines are involved in the brain complications observed in HUS. Inhibition and removal of cytokines by both steroid semi-pulse therapy and blood purification may have a specific therapeutic effect. Since only a few adult cases of HUS complicated by encephalopathy have been reported, and the prognosis is poor, we report this case with the aim of establishing a treatment method in the future.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is tick-borne and caused by the SFTS virus that was newly identified in China. Increasing number of cases of SFTS are being reported in Japan since 2013. We report two cases of SFTS that were expected to severe but good progress with steroid therapy and continuous hemodiafiltration (CHDF) with AN69ST membrane hemofilter at an early stage. Case 1 was of a 83-year-old man. The patient presented with a consciousness disorder on the second day of hospitalization, was shifted to the ICU, and started steroid therapy and CHDF with AN69ST membrane hemofilter, his consciousness disorder was improved, and was shift out of the ICU on the fifth day of hospitalization. Case 2 was of a 68-year-old man. The patient presented with consciousness disorder on the fourth day of hospitalization and was shifted to the ICU; his consciousness disorder was improved with the same treatment, and was shifted out of the ICU on the fifth day of hospitalization. It was thought that providing mathemaical treatment including AN69ST-CHDF at an early stage maintain severe patients clinical status effectively.

【Patient】The patient was a 63-year-old woman who presented with a fever of 39℃ and diarrheal symptoms for the past 8 days. Infectious enteritis was diagnosed at a nearby clinic where she was hospitalized for routine tests. Thrombocytopenia and hemophagocytic images in the bone marrow were observed. Secondary HPS from bacterial infection was suspected, and she was brought to this hospital to be treated for sepsis and DIC. She experienced septic shock during steroid pulse therapy for HPS. PMMA-CHDF for removing mediators such as cytokines and PMX-DHP for removing and inhibiting other mediators such as endotoxin were administered by a series circuit. From initiation to 24h and 48h, her systolic blood pressure (mmHg) increased (75, 110, and 130, respectively), CAI decreased (11.6, 6.1, and 3.9, respectively), and urine output (mL/h) increased (70, 98, and 120, respectively). Hemodynamics improved rapidly, and the pathological condition of HPS trended towards quiescence. 【Conclusion】Hypercytokinemia was considered the cause of the underlying condition of HPS. Treatment with CHDF and PMX-DHP using a PMMA membrane for the purpose of removing and inhibiting mediators such as cytokines at the onset of secondary HPS caused by bacterial infection was effective.

【Background】The core mechanism underlying the pathogenesis of adult Still’s disease is the excessive production of inflammatory cytokines in association with an infection；this results in a loss of control of monocyte and macrophage activation.【Case】An approximately 70-year-old woman was admitted to our hospital because of persistent fever and rash. Oral prednisolone administration was initiated in hopes of reaching a diagnosis. On the 7th day, the patient was diagnosed with adult Still’s disease, and steroid pulse therapy was initiated. The patient’s fever abated immediately, but began reemerging a few days later. Decreased urine volume was also observed at this time. The addition of an immunosuppressive agent to her treatment regimen was ineffective. On the 25th day, continuous renal replacement therapy (CRRT) was initiated for the purpose of removing cytokines, resulting in a prompt reduction in her body temperature. Tocilizumab was used to control the disease condition, and other oral medications such as prednisolone were reduced. The patient was discharged from the hospital on the 58th day, without any recurrence of fever while in hospital. 【Conclusion】Here, we report a case of adult Still’s disease that could be remarkably controlled by a combination of CRRT and tocilizumab therapy. This effect could have been achieved by the adsorption of overproduced cytokines. However, further study is required to substantiate this.

Sepsis-induced cardiomyopathy, in which myocardial trauma is caused by sepsis, has been previously reported and is usually a reversible myocardial disorder requiring several days recovery after sepsis has been cured. We report a case of sepsis-induced cardiomyopathy due to an obstructive urinary tract infection followed by rapid deterioration. The patient’s life was saved by improvement of circulatory dynamics using polymyxin B column-direct hemoperfusion (PMX-DHP) and a polymethyl methacrylate membrane combined with continuous hemodiafiltration (PMMA- CHDF). This intervention removed the need for percutaneous cardiopulmonary support (PCPS). In this case, blood purification therapy rapidly restored cardiac function. Thus endotoxin and cytokine removal using PMX-DHP or PMMA-CHDF should be considered for efficient restoration of cardiac function in cases of life threatening sepsis-induced cardiomyopathy.

A 70-year-old Japanese woman visited her home doctor with a complaint of sustained cough and was diagnosed as having interstitial pneumonia. Seven months later, she was admitted to a regional hospital with complaints of general malaise and appetite loss. Because of the acute deterioration of her renal function (serum creatinine 4.2mg/dL), she was referred to our hospital. On admission, her myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA)≥300U/mL and proteinase3(PR3)-ANCA 9.7U/mL suggested ANCA-positive rapidly progressive glomerulonephritis. After admission, methylprednisolone pulse therapy was administered from day 3. On day 4, she was placed on a ventilator because of respiratory failure with hemoptysis. From day 5, plasma exchange was initiated. On day 18, she was released from the respirator. On days 26 and 57, cyclophosphamide was administered. On day 85, her MPO-ANCA level decreased and her renal function recovered, and she was finally discharged. We describe a case of severe ANCA-associated vasculitis in which the high-grade pulmonary-renal syndrome was successfully treated by quick induction of plasma exchange.

A 43-year-old male was admitted because he experienced a sense of fullness in the abdomen for two weeks. Examination revealed high C-reactive protein level, thrombocytopenia, pleural effusion, ascites, and multiple lymphadenopathies. Although the pathological findings of an axillary lymph node biopsy were consistent with those of hyaline-vascular Castleman’s disease, he was diagnosed with TAFRO syndrome based on clinical characteristics 10 days after admission. Treatment with steroids and tocilizumab was initiated, but his ascites worsened and acute prerenal failure progressed because of hypovolemia despite daily use of albumin preparation. Cell-free and concentrated ascites reinfusion therapy (CART) and hemodiafiltration (HDF) was initiated on the 11th and 19th day after admission, respectively. Ascites was controlled with HDF twice a week and ascites filtration and reinfusion with HDF (AFR-HDF) once a week, and the dose of albumin preparation was decreased. The disease displayed gradual remission with the administration of many types of immunosuppressive therapy, and the patient was discharged from the hospital on the 152th day after admission. No effective treatment for TAFRO syndrome has been established. AFR-HDF can be an effective treatment for TAFRO syndrome in case of refractory ascites and acute renal failure.

We retrospectively compared the effects of treatment conditions between different filtration flow rates (Qf) on filter life as well as those of the treatment itself using a polymethylmethacrylate (PMMA) membrane in patients undergoing continuous hemodiafiltration (CHDF). We used a PMMA membrane in 39 patients undergoing CHDF and classified the patients into one of two groups：low-filtration (LF) group (n=10) and high-filtration (HF) group (n=29). The filter life was significantly longer in the LF group than in the HF group. With respect to parameter changes before and after CHDF, significantly reduced catecholamine index and lactic acid level were found in both groups. As no significant difference was found in the rate of decrease between the groups, improved hemodynamic effects were considered to be equivalent. These findings suggest that improved hemodynamic effects are equivalent if blood purification flow rates are the same, regardless of Qf.

The AN69ST membrane for sepsis patients is covered by insurance and it is expected to be effective. On the other hand, it has become a matter of particular concern that the adsorption of nafamostat mesilate by membranes might shorten the lifetime (lifetime of membranes and blood circuits). A reduced lifetime is associated with several problems such as reduced treatment efficiency, increased workload associated with circuit exchanges, and increased economic burden. In this study, we compared the priming method using nafamostat mesylate in pursuit of the effect of prolonging the lifetime of the AN69ST membrane and the method of anticoagulant addition injection (A/V dispensation method) from the side of blood transmission that has been conventionally carried out. A significant extension of lifetime was therefore recognized using the A/V method.