A team of industry, government, and academic experts worked to change the shape of the plasma port of the plasma separator from a slip-in system (ISO8637) to a luer-lock system (ISO80369-7) as a measure to prevent a recurrence of a 2011 fatal mix-up of the blood purification column. For this conversion, the limited use of intermediate connector to link the old plasma separator and the new blood circuit was approved until the end of August 2020 by the Ministry of Health, Labour and Welfare of Japan. The new plasma separator was launched in September 2019, and the old plasma separator and blood circuit were discontinued in February 2020. This conversion project was promoted by the related academic societies and the MTJAPAN Blood Purification Subcommittee under the guidance of the government. In January 2020, the Central Social Insurance Medical Council reviewed the reimbursement price for plasma separators from a safety supply perspective, and on March, the government announced a revised price. This project provides an important perspective for future product development as an evaluation of safety measures taken collectively by industry, government, and academia.

Until recently, endotoxin (lipopolysaccharides-LPS) shock was not suspected to be caused primarily by the recognition of LPS by cell surface Toll-like receptor (TLR) -4. However, in 2013, intracellular caspase was discovered as a TLR-4-independent LPS sensor. Endotoxin shock can be defined as intracellular caspase-mediated pyroptosis (cell death), caused by intracellular LPS. Recent studies suggested an underlying pulmonary injury mechanism in endotoxin shock, where LPS in the blood is directly transported to the pulmonary vascular endothelial cells, to cause pyroptosis. These studies might imply the significance of removing LPS from the blood. However, even in the EUPHRATES study on polymyxin B direct hemoperfusion (PMX-DHP), the method of direct quantification of LPS was not adopted, and thus, the effect of removing LPS remains unknown. Hence, the outcome of endotoxin adsorption therapy, conducted in patients with high LPS levels, using optimal procedures with appropriate primary endpoints, should be evaluated.

Recent advances shed the light on the chirality of amino acid. D- and L-amino acids have different metabolism pathways and biological functions in the human body. Accumulating study revealed that gut microbiota-derived D-amino acids play key roles in the central nervous system, heart and skin. However, little is known about the roles for the kidney. We explored the pathophysiological functions of D-amino acid, especially D-Serine (Ser), in ischemia-reperfusion induced acute kidney injury. Moreover, we demonstrated that D-Ser could have potential as a novel biomarker for AKI. However, further studies are needed to clarify the potential ability of D-amino acids for progressive kidney diseases.

Metabolic characteristics of acute kidney injury (AKI) are hyperglycemia and increased catabolism of body protein. So, nutritional therapy for AKI patients is essential to lessen energy intake 80％ lower than basal energy expenditure (20-30 kcal/kg BW/day), and increase protein intake greater than 1.2g/kg body weight /day. Since electrolyte abnormality during continuous renal replacement therapy (CRRT) is a risk factor for the development of AKI, comorbidity and mortality, it is necessary to check serum potassium, phosphorous and magnesium routinely. In addition, due to easy loss of water-soluble vitamins and micronutrients from the dialysate, it is important to monitor blood levels of these nutrients in patients on CRRT.

The administrations of circulatory agonists such as epinephrine and norepinephrine are indispensable in shock state induced by various causes including sepsis. Circulatory agonists must be administered in various amounts depending on the hemodynamic state and the kind of the drug. Some severely ill patients are undergoing hemodialysis due to chronic renal failure, or suffer from acute renal failure or acute exacerbation of chronic renal failure, which need blood purification. When using circulatory agonists in patients with severe renal failure or dialysis, 1) grasp the pharmacokinetics, 2) select hepatic metabolic drugs as much as possible, 3) unavoidable When using renal metabolic drugs, it is necessary to adjust the dose and perform blood levels and ECG regularly.

Neonates and children can have a long life after acute blood purification therapy (BPT) and acute kidney injury（AKI）, and it is important to prevent complications to ensure a healthy life. In patients whose renal function declines after acute BPT/AKI, the management of chronic kidney disease is required. In neonates, the detection rate of renal dysfunction early after AKI is low, and follow-up from neonatal to young adulthood is required to detect increases in blood pressure, microalbuminuria, and decreased estimated glomerular filtration rate. In addition, comprehensive growth/development, physical/mental health status, and social adaptation evaluations are required over time and from multiple aspects. When necessary, we provide development support, nursing care, pharmacotherapy, and school and work support. If growth hormone decreases or hypothyroidism occur, treatments such as hormone replacement therapy are provided. After acute BPT/AKI, comprehensive follow-up and supportive care are required with collaboration among specialized pediatric departments. For patients who require long-term intervention, a careful transition to adult care is required.

Although developments in extracorporeal renal replacement therapy (RRT) have extended its use to neonates, several difficulties could emerge in neonatal RRT due to the application of universal RRT machines designed for adults. Neonatal RRT must be performed at low blood flow rates owing to the difficulty in obtaining vascular access. However, in cases where prompt solute removal is desired, a thick vascular access can be obtained through the internal jugular vein, which will enable optimal blood flow and continuous hemodialysis or hemodiafiltration that is not limited by blood flow rates. Meanwhile, for the safety continuous hemodialysis would be chosen to avoid hemodynamic instability, because of long RRT circuit life. The extracorporeal circuit volume of RRT is excessively larger than the circulating blood volume of neonates, thereby putting these patients at risk for hemodilution and hemodynamic instability. Thus, to avoid these complications, the RRT circuit must be primed, prior to neonatal RRT, using artificially packed red blood cells; however it is needed to associated with transfusion-related complications. Neonatal RRT devices are used clinically in Europe and have been shown to be effective and might improve the prognosis of neonates in the future. Japan is currently developing an ultra-small neonatal RRT device but is yet to analyze its effectiveness in the clinical setting. We hope that small-volume RRT devices for neonates will continue to be developed and applied in the clinical settings.

The incidence of acute kidney injury (AKI) as diagnosed by international standardized criteria as well as its mortality have undergone extreme variations. Although AKI is a significant worsening mortality factor, a higher prevalence may lead to better patient management, thereby lowering mortality. Here, we investigated the correlation between AKI incidence and its associated mortality. We conducted a systematic review of studies on AKI reporting its incidence and mortality. Literature searches were performed in PubMed, EMBASE, and Cochrane Library, within the time frame of 2004 to 2018. The correlation among AKI incidence, mortality, and AKI-attributable fraction of mortality was evaluated using a regression model. Subgroup analysis on adult ICU patients was also performed. As a result, 287 cohorts were eligible (adults: 203 cohorts comprising 7,076,459 patients; children: 84 comprising 69,677 patients) . Within adult cohorts, AKI patients’ mortality increased (regression coefficient (β)= 0.12, P=0.03) but the attributable fraction of mortality decreased (β=−0.43, P＜0.001) with the increasing AKI incidence. In adult ICU cohorts, the mortality of patients with AKI significantly decreased (β=−0.25, P＜0.001) as the incidence of AKI increased. In conclusion, cohorts with high AKI incidence had a relatively low mortality attributable to AKI, which suggests an advantage of frequent AKI occurrence and more experienced AKI management. Further study is needed, however, to address the heterogeneity of included cohorts and to confirm the causality.

Various types of dialysis membranes are used in continuous hemodiafiltration (CHDF), including polysulfone (PS) membranes, polymethylmethacrylate (PMMA) membranes, and acrylonitrile (AN69ST) membranes. Each type of membrane has a characteristic structure and differences in the adsorption and filtration properties for these membranes have been reported. In this study, we focused on proteins in filtrate during CHDF and proteins adsorbed to the membranes after CHDF in order to assess the adsorption and filtration characteristics of PS, PMMA, and AN69ST membranes. Subjects were patients with sepsis or septic shock who underwent CHDF. Proteins in filtrate and proteins adsorbed to the surface of membranes were evaluated using filtrate samples taken during CHDF and hollow fibers removed from the membranes after CHDF. We found that the AN69ST membrane preferentially adsorbed proteins with wide isoelectric points, and the PMMA membrane had a preference for high molecular weight proteins. The PS membrane had a very high filtration efficiency, in particular, for proteins with a molecular weight of up to about 10 kDa. These differences suggested the involvement of membrane structure and protein binding properties, as well as differences in the negative charge of the membranes. The properties uncovered in this study may be involved in the mechanisms underlying the anti-inflammatory effects of these membranes.

Streptococcal toxic shock syndrome (STSS) is a critical disease with a high mortality rate in which multiple organ dysfunction, including acute kidney injury (AKI), progresses rapidly. The incidence of STSS in Japan has been increasing in recent years. We encountered five cases of STSS complicated with AKI at the Saitama Medical University International Medical Center. All cases involved septic shock and disseminated intravascular coagulation. Blood purification therapy was administered to four patients. These patients recovered from AKI and survived to discharge. However, one patient developed cardiopulmonary arrest and was transported; the patient died before the initiation of blood purification therapy. The progression of STSS is extremely rapid; thus, positive patient prognosis relies heavily on prompt and appropriate treatment.

An 87-year-old man was transferred to our hospital because he could not move. He was diagnosed with influenza A infection and admitted to our department. The levels of serum creatinine (Cr) and creatine phosphokinase were elevated from 1.07mg/dL and 7,542U/L to 2.5mg/dL and 96,700U/L on the second day of hospitalization, respectively. T2 fat suppression muscle magnetic resonance imaging showed high-intensity signals in the trunk and thigh muscles. Therefore, he was diagnosed with acute kidney injury due to rhabdomyolysis associated with influenza A infection. Hemodialysis was initiated on the fourth day of hospitalization because of oliguria and increase in serum Cr level to 6.8mg/dL. Hemodialysis was performed 14 times in 28 days and finally withdrawn. On the 50th day of hospitalization, he was discharged. Although rhabdomyolysis is one of the complications associated with influenza infection, it rarely leads to severe acute kidney injury that requires hemodialysis. Here, we report a case of rhabdomyolysis and severe acute kidney injury complicated by influenza A infection.

The AN69ST membrane hemofilter has been reported to absorb nafamostat mesilate (NM). To prevent such absorptions, our hospital adopts a 2-way method wherein NM is injected into the venous side as well. The success rate of the conventional 2-way method was as high as 94% when dialysis was performed with 1 hemofilter for 22 hours or longer, but the required dose of NM was high 41.0 ± 9.7 mg/hr. Activated clotting time before and after the hemofilter was not extended, but the venous chamber was the site of the coagulation in all subjects in whom the target could not be achieved; notably, no coagulation was observed in the hemofilter. Based on the above findings, we inferred that the AN69ST membrane was a hemofilter with excellent anticoagulant ability and prepared a new protocol that substantially reduced NM on the arterial side. The target achievement rate of the new protocol was 95％. Compared to the conventional protocol, the NM dose could be reduced by 55％ to 18.5±2.4 mg/hr without increasing the circuit clotting.

【Background】Continuation of CRRT may extend the time to death but may not necessarily be a treatment that meets the patient’s and family’s will and wishes when the patient is not able to survive without CRRT. We evaluated the appropriateness of CRRT termination in ICU death cases. 【Methods】Among CRRT patients who stayed in the ICU for seven days or more, the timing of CRRT termination and the duration from the end of CRRT to death were examined in death cases. 【Results】Of sixty-five patients, CRRT was terminated in seventeen patients (26%) before death. CRRT was terminated after informed consent from the patient’s family following a conference by multi-occupations about the patient’s condition. The median duration from CRRT termination to death was 201 minutes. 【Discussion & conclusion】Different from ventilators and assisted circulators, the termination of CRRT is less likely to lead directly to death of the patient. If deterioration of the patient’s condition has been suppressed by CRRT, however, termination of CRRT may define the time to death. When a patient is considered to be in the terminal stage of disease, we should present the possibility of being unable to save life, and support to allow time for the family to be fully convinced.