Acute kidney injury (AKI) frequently occurs in critically ill patients with multiple organ failure in ICUs. AKI complicated with sepsis and multiple organ failure has been recognized as a syndrome related to both nephrology and critical care medicine. The establishment of a closer relationship between intensivists and nephrologists and the establishment of training programs for both fields has been suggested, with the designation of “critical care nephrology.” In Japan, critical care nephrology has developed with acute blood purification therapy in ICUs. AKI can result from different etiologies in diverse clinical contexts. Its impact on clinical outcomes is huge. Therefore, a multidisciplinary approach that integrates critical care medicine, nephrology, and blood purification must be undertaken to improve the management of AKI in clinical practice.

High Mobility Group Box 1 (HMGB1) is released from various cell types and acts as a pro-inflammatory ligand of Toll-like receptors and receptors for advanced glycation end-products. HMGB1 accelerates inflammation during sepsis, disseminated intravascular coagulation (DIC) and multiple organ failure; this often occurs via HMGB1-mediated crosstalk between inflammatory and coagulant processes. We assumed that HMGB1 metabolism was not predominantly dependent on renal function and, therefore, the degree of HMGB1 regulation in blood was independent of urine outflow. During septic shock, Polymyxin-B direct hemoperfusion (PMX-DHP) ameliorates any harmful effect on hemodynamics by not only endotoxin but also endogenous cannabinoid adsorption, and also improves pulmonary oxygenation by the indirect reduction of cytokines (IL-6, HMGB1, etc.) after the adsorption of activated mononuclear cells. However, whether PMX-DHP also directly adsorbs HMGB1 remains controversial; we therefore investigated this possibility at both the clinical and basic science levels, and found that PMX-DHP had no significant, direct effect on blood HMGB1 levels. In DIC, recombinant thrombomodulin (rTM), a very effective drug for this disease, exerts not only anticoagulant but also anti-inflammatory effects via direct anti-HMGB1 activity. Therefore, a combination of PMX-DHP and rTM for the treatment of DIC is expected to block the vicious cycle of a cytokine storm ending up and consequent multiple organ failure. Such combination therapy is effective in septic shock that is accompanied by DIC and is expected to improve patient survival rates.

Teicoplanin (TEIC) is an antibiotic that require high-dose loading at the start of treatment. The effect of continuous renal replacement therapy (CRRT) with a polymethylmethacrylate (PMMA) membrane on TEIC serum concentration (TEICc) in a high-dose regimen has not been clarified. Hence, we investigated the change in TEICc in the high-dose regimen under CRRT with a PMMA membrane. Our results indicated that TEIC elimination with the PMMA membrane affected the TEICc. Under CRRT with a PMMA membrane, the high-dose regimen reached the target area of the TEICc early.

【Objective】 We investigated the efficacies of recombinant thrombomodulin (rTM) during the Polymyxin B immobilized fiber column direct hemoperfusion (PMX-DHP). 【Method】 We retrospectively reviewed the medical records of patients who had been undergone PMX-DHP. All patients were divided into two groups: PMX-DHP with rTM, and PMX-DHP without rTM. The patient characteristics, outcomes, and changes of catecholamine needs, and platelets count were compared between two groups. 【Results】 There was no difference in the 28-day mortality between two groups. There was more decrease in catecholamine needs after the initiation of PMX-DHP in the group treated with rTM than the group without rTM. Although there was no statistical significance, the platelets count tended to recover when patients were treated with rTM. 【Conclusion】 In our study, rTM therapy combined with PMX-DHP showed no obvious positive effect on patients with septic shock. Further prospective study should be warranted to prove our hypothesis.

Results of recent studies suggest that acute kidney injury (AKI) increases the risk of chronic kidney disease (CKD) development and progression, but what biomarker, if any, can predict CKD progression in AKI survivors remains unclear. This prospective observational study examined data of 495 adult patients admitted to the ICU of our hospital. We respectively evaluated long-term renal outcomes of halving of the estimated glomerular filtration rate and incident end-stage renal disease. Of the 495 patients, 169 were followed-up for three years after ICU discharge. Among them, 30 (17.8%) showed CKD progression. Three urinary biomarkers were measured at ICU admission: L-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl-β-D-glucosaminidase (NAG). Progressors showed significantly higher L-FABP and NGAL levels. Step-wise multiple logistic regression analysis revealed that only urinary L-FABP was associated significantly with CKD progression after ICU discharge. Receiver operating characteristic analysis showed the area under the curve of urinary L-FABP as 0.69 (95%CI 0.57-0.78). Results of this three-year follow-up study clarified that measurement of urinary L-FABP at ICU admission is useful for predicting long-term renal function after ICU discharge, and that high-risk populations should be monitored closely at outpatient clinics.

Continuous blood purification therapy (CBP) is widely applied mainly in the field of intensive care and has been an essential method of achieving acute blood purification. However, it is also a reality that CBP is applied by trial and error, resulting in differences among facilities. The Tokai study group for continuous hemodialysis and filtration (CHDF) has attempted to share information on CBP through clinical conferences and the results of questionnaire surveys since 2008. In 2014, the 6th questionnaire survey was conducted to investigate the current status of CBP in the Tokai region. The questions were related to conditions of CBP, priming methods, and management systems for this procedure. Despite the differences in conditions, priming methods and cases, certain trends in the conditions, management methods, and so on, were revealed. The survey also revealed that management regarding changes in drugs and conditions during CBP, as well as handling of problems, is dealt with by clinical engineers at many facilities, suggesting that CBP is dependent on the staffing levels of on-duty clinical engineers. It appeared that we clinical engineers should also become involved, in the future, in standardization of CBP from our perspectives.

We investigated for cytokine absorption removal and circuit interval pressure of polymethymethacrylate (PMMA) membrane hemofilters with two different membrane surface area. We compared HEMOFEEL^® CH-1.0N(1.0m²) with HEMOFEEL^® CH-1.8W (1.8m²). Criteria for inclusion were patients who had surgery of generalized peritonitis with hypercytokinemia which IL-6 level is not less than 10,000pg/mL but not more than 100,000pg/mL at the start of continuous hemodiafiltration. It was analyzed from 11 cases using CH-1.0N and 9 cases using CH-1.8W. We made a comparative review of IL-6 level, inner circuit pressure, hemofilter life time, and 28 days survival rate at the beginning of the continuous hemodiafiltration, 6 hours later, 12 hours later, and 24 hours later. The data demonstrated that IL-6 level with the use of CH-1.8W increased to 1.3 times.

We evaluated the interleukin (IL)-6 adsorption ability of the polymethyl methacrylate (PMMA) hemofilter “Hemofeel CH-1.8W” (Toray Industries, Inc.), which has been used clinically since October 2013. 【Subjects】 We assessed 10 patients who received continuous renal replacement therapy (CRRT) with Hemofeel CH-1.8W whose IL-6 levels were ＞1,000pg/mL at 15min after the start of CRRT. 【Methods】 We measured IL-6 clearance at 15min, 1h, 24h and 48h after therapy commencement. 【Results】 Mean IL-6 clearance (mL/min) was 41.95±7.70 at 15min, 21.50±10.11 at 1h, 8.67±2.67 at 24h, and 13.34±16.77 at 48h. 【Conclusions】 IL-6 clearance was reduced significantly at 24h and 48h. These data suggest that the filter should be changed every 24h to keep its high adsorption performance.

We examined the dosage of anticoagulant given to a patient with thrombotic thrombocytopenic purpura (TTP) undergoing a combination of plasma exchange (PE) and hemodialysis (HD). The patient was a man in his seventies in whom HD was initiated for acute kidney injury in September 2011 and PE was initiated following a diagnosis of TTP in October of the same year. Due to the delirium symptoms, the patient underwent a combination of PE and HD 25 times from November 2011 to shorten his treatment time. The circuit was configured with the HD circuit as the base and the PE circuit was connected in a quasi-series before HD. Nafamostat mesylate (NM) was used as an anticoagulant. Activated clotting time (ACT) was measured and compared (1) before the plasma separator, (2) after the plasma separator, and (3) at the dialyzer outlet when NM was administered at 30mg/h from both the PE and HD circuits and when NM was administered at 30 mg/h from the PE circuit alone. Results revealed that ACT at the dialyzer outlet was approximately 330 s on an average irrespective of the NM dosage. In addition, no coagulation was observed within the circuit. The patient was safely treated with a reduced dosage of anticoagulant by combining PE and HD.

We experienced a case in which cryofiltration (CF) was performed for hepatitis C-associated cryoglobulinemia. Herein, we report the procedure and its therapeutic effect. The patient was a 68-year-old man who was positive for hepatitis C virus, rheumatoid arthritis, purpura on the lower limbs, and the cryoglobulin qualitative test, showing a course consistent with rapid progressive glomerular nephritis. After 2 CF sessions, his renal function showed a trend towards improvement; purpura on the lower limbs resolved, and pain was also alleviated. For hepatitis C-associated cryoglobulinemia, aggressive application of CF resulted in improved local circulation, which contributed to improved renal function and resolution of low limb purpura. In order to control the temperature of plasma, a cooling system for an artificial heart-lung machine was used. By controlling the surface temperature of the plasma circuit in a range of 15～20℃, we were able to keep the target temperature in a range of 4～10℃.

Insufficient bilirubin adsorption due to the performance limit of the devices and/or fibrin Precipitation is sometimes experienced. We report a case of post-operative liver failure. The patient underwent plasma bilirubin adsorption therapy using selective membrane plasma separator Evacure EC-4A10 as a primary filter. Bilirubin adsorption was performed 7 times, processing 30L of plasma per procedure. The time course changes of total bilirubin (T-Bil), fibrinogen (Fib), and platelet (Plt) were examined. The mean decreasing-rate of T-Bil after treatment was 53.6% (range: 45.5〜61.4%). The change of serum Fib and Plt were ranged within from −22% to ＋22% and within from −15% to ＋31%, respectively. It is suggested that fibrin deposition and hemolysis were prevented effectively by using Evacure EC-4A as a primary filter for plasma adsorption therapy.

We present a case of a 62-year-old woman who developed severe septic shock following flexible transurethral lithotripsy (f-TUL), showing favorable response after multidisciplinary treatment consisting mainly of acute blood purification therapy. The patient underwent f-TUL for nephrolithiasis of the right kidney. The operation was completed with no specific intraoperative complications. Blood pressure decreased and clouding of the consciousness as observed the day after the operation. Hematological examination showed high-level acute inflammatory reaction and lower platelet counts, indicative of severe septic shock and disseminated intravascular coagulation (DIC). The patient was transferred immediately to the intensive care unit (ICU). Multidisciplinary treatment comprising continuous hemodiafiltration (CHDF) and endotoxin adsorption therapy (PMX) was administered. The treatment was successful. The patient recovered from DIC at an early stage and left the hospital at 34 days after the operation. Risk of complication is expected to increase with the spread of f-TUL. Prompt action including acute blood purification therapy must be taken.

Using a 1.0m² and 1.8m² PMMA membrane hemofilter, a comparative study was made on life-time and each type of pressure value. A crossover was made using CH-1.0SX, CH-1.8W. Setting blood flow at 100mL/min, dialysate at 570mL/hr and filtration flow at 100mL/hr, ACT was controlled to be 200～350s on the retransfusion side. Pressure values of inlet-venous difference pressure, transmembrane pressure (TMP) were compared, and timing of circuit switching set at inlet pressure 350mmHg and greater, TMP 250mmHg and greater, and past 48 hours. Using Wilcoxon signed-rank sum test for statistical examination, p-value＜0.05 was considered as showing a significant difference. No case of circuit coagulation during CHDF was noticed, nor significant difference in operating time. Significant difference was seen in pressure values of both inlet-venous difference pressure and TMP. Different membrane surface areas didn’t show any difference in life-time, but both inlet pressure and TMP showed low values with CH-1.8W, indicating expectations for prolonged life-time, so further studies should be made.

As a first step to improving the spontaneous survival rate of acute liver failure (ALF), we developed an on-line continuous hemodiafiltration (CHDF) system to recover ALF patients from hepatic encephalopathy. It is necessary to maintain the biological safety of the dialysate when performing on-line CHDF therapy at the bedside in the ICU. For this purpose, two endotoxin retentive filter apparatuses and an automatic cleaning program in the off-period were incorporated into the dialysis machine, which was then fixed exclusively to one reverse osmosis machine. In addition, the control system for monitoring the dialysate flow rate and replacement volume was improved to more precisely fit 24 hours of operation in a relatively low flow rate mode compared with conventional hemodialysis. These mechanical improvements resulted in the capacity to make 288L per day of dialysate and divert 0～170L per day from the dialysate for fluid replacement. A clinical examination is planned to validate the utility of this machine in recovering ALF patients from hepatic encephalopathy.