Acute kidney injury (AKI) requiring renal replacement therapy (RRT) has a poor prognosis, as indicated by its mortality rate of 50%～60%. Biomarkers for early detection, prediction of prognosis and guidance of treatment have been proposed as a novel strategy for AKI. Another strategy is to administer RRT for an appropriate term, as treatment could be discontinued for most patients with AKI. Although repeated RRT administration is a poor prognostic factor, repeated administration is necessary in 30％～40％ patients after discontinuation. Therefore, a practical biomarker to indicate appropriate RRT discontinuation is useful. Decreasing levels of urinary neutrophil gelatinase-associated lipocalin (NGAL) and hepatocyte growth factor (HGF) in 7days and 14days from starting RRT have recently been reported to predict RRT discontinuation. A panel of urinary biomarkers combined with clinical parameters may be a useful tool to indicate RTT discontinuation.

The incidence of acute kidney injury (AKI) has increased annually, and the prognosis of AKI is particularly poor in cases arising in intensive care units (ICU). Implementation of blood purification does not necessarily improve the outcome of AKI, and the successive and concurrent impairment of various distant major organs such as the heart, lung, brain and liver is thought to be a factor associated with poor prognosis. In the intervention of AKI, it is therefore quite important not only to consider the indication of renoprotective and renal replacement therapies, but also to constantly monitor the possible onset of major organ impairment. Inflammatory mediators play a key role in the mechanism common to the onset of distant organ impairment caused by AKI. The inflammatory mediators induced as a result of ischemic injury and various other injuries in the kidneys are not only involved in injury localized to the kidneys, but they activate systemic innate immunity as well. Consequently, in addition to activation of Toll-like receptors, reactive oxygen species, and complements, inflammatory mediators also promote the expression of chemokines specific to each organ and induce the activation of neutrophils and macrophages, ultimately leading to abnormalities in the physiological function of each distant organ. In cases of multiple distant organ disorders due to AKI, multiple inflammatory mediators, which are most notably associated with systemic inflammatory response syndrome (SIRS), are produced, and treatments targeting a single mediator may not be expected to be sufficiently effective. Therefore, with the objective of eliminating inflammatory mediators, it has been considered important to implement hemofiltration (as a non-renal indication) from an early stage before indication of blood purification in patients at risk of developing multiple organ failure due to AKI.

Continuous renal replacement therapy (CRRT) plays a crucial role in the treatment of acute kidney injury (AKI) occurring in an ICU. Many clinical researchers who have examined CRRT treatment settings and CRRT initiation timing have provided verifiable results, but some critical issues remain unresolved. This article presents a review of the evidence reported to date related to 1) advantages of CRRT against intermitted dialysis, 2) early initiation, 3) optimal therapeutic dose and its evaluation, and 4) hemofilter selection. Moreover, discussion of this topic, which demands further clinical investigation, is presented. Determining the best CRRT treatment settings and CRRT initiation timing depends on the condition of each AKI patient. Nevertheless, such choices should always be based on evidence. Further investigation must be conducted to establish new evidence related to these issues, which has been evaluated only insufficiently in clinical research to date.

Renal replacement therapy (RRT) for critically ill patients with acute kidney injury (AKI) is provided as either intermittent renal replacement therapy (IRRT) or continuous renal replacement therapy (CRRT). Intermittent hemodialysis (IHD), which is a typical modality of IRRT, is often complicated by hypotension and inadequate fluid removal. Sustained low-efficiency dialysis (SLED) is a novel RRT appropriate for a broad range of solutes and volume removal. SLED is a slower dialytic modality run for prolonged periods (6- to 12-hour) using conventional hemodialysis machines with modification of blood and dialysate flows. SLED allows units where CRRT equipment or personnel are unavailable to offer a treatment modality that should achieve similar benefits as CRRT. Although SLED can technically be classified as a type of IRRT based on treatment duration, it combines the advantages of IRRT and CRRT and affords better hemodynamic stability, correction of hypervolemia, and solute removal. In Japan, we need to consider the definition and positioning of SLED as one of the RRT modalities.

High mobility group box 1 (HMGB1) is released from various types of cells and is a pro-inflammatory ligand of Toll-like receptors and receptors for advanced glycation end products (RAGE). It is known that HMGB1 accelerates inflammation during sepsis and disseminated intravascular coagulation (DIC). Polymyxin B immobilized fiber column direct hemoperfusion (PMX-DHP) is an effective therapeutic modality for sepsis by directly adsorbing endotoxin. However, whether or not PMX-DHP directly adsorbs HMGB1 remains controversial. In order to answer this question, we measured time-dependent and column-dependent changes in serum HMGB1 concentration in the clinical setting. However, we did not see any significant reduction in serum HMGB1 level. Next, we investigated the effects of polymyxin B-immobilized fiber on HMGB1 concentration in experimental HMGB1 solution in vitro. Consistent with the clinical data, there was no significant adsorption of HMGB1. We conclude that PMX-DHP does not directly reduce the blood HMGB1 level during treatment. Its remote effect may play an important role in regulating HMGB1.

Acute kidney injury (AKI) remarkably increases mortality of critically ill patients treated in intensive care unit (ICU). Recently, several biomarkers have been developed for the early detection of AKI. There are few reports which evaluate the serial measurement of new biomarkers. Urinary L-type fatty acid-binding protein (L-FABP) as a new biomarker of AKI has approved to be reimbursement since 2011 in Japan. We prospectively studied 274 adult critically ill patients, 159 (58.0%) of whom were diagnosed as AKI. Urinary L-FABP was measured at ICU admission and 24 hours later. The minimum of urinary L-FABP is the most useful for detecting the worsening AKI and severe AKI requiring CHDF. These results show that serial measurement of urinary L-FABP can contribute to predict the poor outcomes of AKI in ICU patients.

In recent years, use of blood purification systems with monitoring of the blood removal status based on changes of the blood removal pressure has become popular. However, there are no reports on the influence of differences of the blood removal pressure on the actual blood flow rate among 3 blood purification systems manufactured by Asahi Kasei Medical Co., LTD., ACH-Σ^® (hereafter referred to as Σ), Plasauto iQ21^® (iQ), and Plasauto LC^® (LC). Therefore, we studied the influence of changes of the blood removal pressure on the actual blood flow rate for these systems.［Methods］The blood pump flow rate was set at 50, 80, 150 and 200mL/min, and the blood removal pressure at －70, －100, －150, and －250mmHg. The weight of a mimic blood discharged for one minute was measured 3 times each with an electronic balance. The actual blood flow rate was calculated from the mimic blood weight and the relative flow rate error was obtained using the formula, {(actual flow rate−blood pump setting flow rate)/blood pump setting flow rate}×100. [Results] Regression equations revealed the following relationships between the relative flow rate error (y) and blood removal pressure (x): Σ: y＝0.0249x－3.694, iQ: y＝0.0384x＋4.544, LC: y＝0.0417x＋0.666. [Conclusion] The slope of the regression equation for Σ was smaller than the slope values for iQ and LC, therefore, Σ may be said to not be influenced by the blood removal pressure. These findings have implications for the understanding of each device characteristic because of each device affect the different actual flow rate on the blood removal pressure.

Dialysis efficiency of continuous hemodiafiltration (CHDF) basically depends on the amount of dialysate and ultrafiltration flow. Small membrane surface area (MSA) hemofilter is expected to benefit the patients with unstable hemodynamics because of the smaller amount of priming volume, but how the size of MSA contributes to the efficiency and durability of CHDF is still unknown. To elucidate the benefit and the effect of small MSA hemofilter on CHDF in critical settings, we conducted two-story studies. The first step is the preliminary saline-based experiment in vitro to elucidate the determinants of dialysis efficiency. In this study, the amount of dialysate was limited to the extent of the reimbursement. Consequently, we found only the amount of dialysate determine the dialysis efficiency. Thus, neither the size of MSA nor the amount of blood flow was the determinant of the efficiency. Based on the preliminary results, we scrutinized and compared 37 small MSA filter (AEF03, Asahi-kasei Co.Ltd, Tokyo, Japan) and 32 large MSA filter (AEF07 Asahi-Kasei Co.Ltd) used in our Hospital in terms of the life-time and inter-circuit pressure. Consequently, we found the small MSA filter AEF03 comparable to AEF07. According to these two studies, we suggest that AEF03 be less invasive because the former is expected to yield the stabilization of hemodynamics without reducing the dialysis efficiency. We supposed that the benefit of small MSA is attributable to the reduction of priming volume, and blood loss retained by the circuit as well as the exposure time of the blood to the external environment.

A patient died due to a mistake in the replacement of a blood purification device in November, 2011 at Kyoto University Hospital. In this article, the accident is briefly reviewed, and recurrence prevention measures presently implemented are described. The patient was a male in his fifties with decompensated liver cirrhosis undergoing chronic maintenance hemodialysis. He was emergently admitted as a brain-dead donor was found while he was waiting for a liver transplantation. Following partial brain-dead liver transplantation, continuous hemodiafiltration (CHDF) was initiated. On the 7th postoperative day, a plasma separator was mistaken for a hemofilter in the replacement of the CHDF channel, causing rapid exacerbation of the condition and death of the patient 13 hours after the replacement. Post-hoc examination revealed problems including: (1) poor management of materials that can be mixed up, (2) inadequacy of the CHDF execution system, and (3) inability to detect the cause of the rapid exacerbation of the condition until the death of the patient in holiday and night medical examinations. As a result, a 24-hour system for CHDF channel assembly by clinical engineers was established, a manual of the CHDF procedure to be shared by the entire hospital was prepared, and education of the staff in blood purification therapy was intensified.

Acute kidney injury (AKI) is a frequent and severe complication after cardiovascular surgery. Indications of continuous renal replacement therapy (CRRT) for patients with AKI have been proposed. However, there is often less discussion of when to discontinue CRRT as well as what conditions are required for transferring to intermittent hemodialysis (HD). In this retrospective study of electronic medical records, we examined on the effects between presence or absence of mechanical ventilator support and re-introduction of CRRT in patients with AKI. When CRRT was stopped, 32 patients were supported with a mechanical ventilator while 41 patients had no support. The rate of change in body weight after the surgery were higher, sequential organ failure assessment (SOFA) score was higher and central venous pressures were higher in patients supported with a ventilator (all were p＜0.05). The rate of re-introduction to CRRT was higher (p＜0.01) in patients supported with a ventilator. The adjusted odds ratio to re-introduction was 5.20 (95%CI: 1.15～23.4). These data suggest that the presence or absence of mechanical ventilator support in addition to evaluation of renal function should be considered when CRRT is discontinued.

We report 2 cases of hypothermia treated in which the patients were successfully rewarmed by hemodialysis. Case 1: The patient was a male in the 7th decade of life who was found lying on the floor at his workplace and was brought to our hospital. On arrival, his consciousness level was JCS 3, and his GCS score was 11 points. His body temperature was 28.4℃, systolic blood pressure 80mmHg, blood urea nitrogen 139.8mg/dL, and serum creatinine 19.72mg/dL. Hemodialysis was initially performed with a 34.6℃ dialysate, and its temperature was gradually raised to 39.0℃. At the end of a 3-hour dialysis session, body temperature had risen to 33.5℃. Case 2: The patient was a male in the 7th decade of life who was found lying on the ground in a park early in the morning by a police officer on patrol and was brought to our hospital. On arrival, his consciousness level was JCS 100, and his GCS score was 8 points. His body temperature was 27.5℃, and his systolic blood pressure was unmeasurable. Hemodialysis was initially performed with a 37.5℃ dialysate, and its temperature was gradually raised to 39.0℃. At the end of a 2-hour dialysis session his body temperature had risen to 33.3℃. Rewarming was achieved safely in both cases by raising the temperature of the dialysate by 1.6～1.7℃ per hour. We concluded that hemodialysis is useful as a means of safely rewarming hypothermia patients as other methods of extracoporeal circulation.

[Background] The use of columns is the predominant method of treatment in the removal of white blood cells (WBC), but limitations are known to exist regarding the processing volume. In this study, the authors implemented a WBC removal therapy using centrifugation in regard to a patient with acute lymphocytic leukemia, who emonstrated an abnormally high WBC count, in an attempt to achieve a speedy remission. [Case] 39-year-old male. He visited a local clinic for consultation due to palpitations and shortness of breath occurring. He was thereafter transferred to this hospital under emergency conditions with a suspicion of leukemia. On arrival, the patient was alert, with blood pressure of 128/64mmHg, temperature of 37.5℃, respiratory rate 20 breaths/min, and SpO2 94% (RA). Blood tests showed a WBC count of 438,500/μL, a red blood cell count of 1,520,000/μL, hemoglobin level of 4.3g/dL, hematocrit level of 12.7%, a blood platelet count of 16,000/μL and a PT-INR level of 1.34. [Method] We used a COBE^® Spectra (TERUMO BCT) ultracentrifuge, taking blood access from both upper limb veins, and implementing centrifugation using ACD-A liquid anticoagulant. [Results] After centrifugation the WBC fell to 177,100/μL. [Conclusions] It was suggested that the therapy using centrifugation could also lead to a curative effect safely.

The symptoms of nafamostat masilate (NM) hypersensitivity are diverse and range from minor ones such as chills to severe ones such as shock. Although discontinuation of NM is considered when minor symptoms of NM hypersensitivity appear, NM is sometimes used with careful observation because of concerns regarding the exacerbation of bleeding tendency due to changes in heparin. At present, it is impossible to diagnose as NM hypersensitivity at the bedside. A non-invasive continuous hematocrit monitor has been widely used as a method to detect blood volume variations (ΔBV) during hemodialysis. We experienced one case who was presumptively diagnosed with NM hypersensitivity, in whom ΔBV showed paradoxical variations that were unrelated with water removal. A 73-year-old man with end-stage of renal disease started hemodialysis 7 years ago. He had used NM at the initiation of dialysis. He was admitted to our hospital, because of intractable pleural effusion. The anticoagulant was changed in NM from heparin because of the presence of bloody plural effusion. During every dialysis therapy using NM, an acute and atypical change in ΔBV was observed with the emergence of chills and trepidation approximately 60 minutes after the start of dialysis. When the anticoagulant was changed in heparin, these symptoms and change in ΔBV were not observed. Subsequently, the patient was diagnosed as being positive for NM specific IgE antibodies.