Association between glycated albumin and sudden death in patients undergoing hemodialysis.

BACKGROUND: The frequency of sudden death and its risk factors in patients undergoing hemodialysis are unknown. This study was performed to examine the association between glycated albumin (GA) and sudden death in Japanese patients undergoing hemodialysis. METHODS: In total, 260 patients undergoing hemodialysis aged ≥18 years were retrospectively followed for a mean of 4.6 years. The patients' serum GA levels were divided into tertiles, and the patients' sex, age, albumin level, C-reactive protein (CRP) level, and cardiothoracic ratio (CTR) were selected as adjustment factors. A logistic regression model was used to calculate the odds ratio (OR) for the occurrence of sudden death by GA level. RESULTS: Ninety-one patients died during follow-up. Of the 91 deaths, 23 (25.2%) were defined as sudden deaths. Compared with non-sudden death cases, sudden death cases were significantly younger (p = 0.002) and had a higher proportion of men (p = 0.03), a higher proportion of diabetes (p = 0.008), and higher GA levels (p = 0.023). Compared with patients with the lowest GA levels (<15.2%), those with the highest GA levels (≥18.5%) had a sex- and age-adjusted OR for sudden death of 5.40 [95% confidence interval (CI): 1.35-21.85]. After adjusting for the albumin level, CRP level, and CTR in addition to sex and age, the OR for sudden death of patients with the highest GA levels increased to 6.80 (95%CI: 1.64-28.08); the relationship did not change. CONCLUSION: Serum GA levels were significantly associated with sudden death in patients undergoing hemodialysis.

Clinical study of blood purification therapy in critical care in Japan: results from the survey research of the Japan Society for Blood Purification in Critical Care in 2013.

To clarify the clinical status of blood purification therapy (BPT) in critical care in Japan, we conducted a cohort study using data from a nationwide registry of the Japan Society for Blood Purification in Critical Care in 2013. We enrolled 2227 patients treated with BPT (female, 39.1%; mean age, 65.5 ± 12.1 years) in the intensive care units of 43 facilities. Patient characteristics, modes of BPT, and survival rate for each disease were investigated. In total, BPT was performed 3053 times. Continuous renal replacement therapy (CRRT) (57.9%) was the most common mode of BPT, followed by intermittent renal replacement therapy (20.2%) and direct hemoperfusion with the polymyxin B-immobilized fiber column (PMX-DHP) (11.5%). Nafamostat mesilate (84.9%) was most frequently used as the anticoagulant. The 28-day survival rate was 56.8% in all patients. The most common mode for acute kidney injury (AKI) and multiple organ failure was CRRT, while PMX-DHP and CRRT were most common for sepsis. There was no significant difference in survival rates among AKI stages 1-3. Survival rate (38.3%) was significantly lower in patients with acute lung injury (ALI) than in those with multiple organ failure (41.8%) and those with sepsis (46.6%). Multivariate regression analysis revealed that the APACHE II score and the presence of acute ALI and acute hepatic failure were significantly associated with death. This large-scale cohort study showed the clinical status of BPT in Japan. Further investigations are required to clarify the efficacy of BPT for critically ill patients.

Angiotensin receptor blocker (ARB)-diuretic versus ARB-calcium channel blocker combination therapy for hypertension uncontrolled by ARB monotherapy.

Diuretics or calcium channel blockers (CCBs) are used concomitantly with an angiotensin II receptor blocker (ARB). However, it is not established which ARB-based combination therapy is the most effective and safe. This prospective randomized open-label study compared the efficacy and safety of a fixed-dose tablet of losartan (LST)-hydrochlorothiazide (HCTZ) (n = 99) and LST-amlodipine (AML) (n = 77) in Japanese patients whose hypertension was uncontrolled by ARB monotherapy. Blood pressure changed similarly over the 12-month study period. Only LST-HCTZ significantly increased serum uric acid (SUA) in patients with low baseline SUA (<5.6 mg/dL) but not in patients with high baseline SUA.

Comparison of sustained hemodiafiltration with continuous venovenous hemodiafiltration for the treatment of critically ill patients with acute kidney injury.

Despite improvements in medical care, the mortality of critically ill patients with acute kidney injury (AKI) who require renal replacement therapy (RRT) remains high. We describe a new approach, sustained hemodiafiltration, to treat patients who suffered from acute kidney injury and were admitted to intensive care units (ICUs). In our study, 60 critically ill patients with AKI who required RRT were treated with either continuous venovenous hemodiafiltration (CVVHDF) or sustained hemodiafiltration (S-HDF). The former was performed by administering a postfilter replacement fluid at an effluent rate of 35 mL/kg/h, and the latter was performed by administering a postfilter replacement fluid at a dialysate-flow rate of 300-500 mL/min. The S-HDF was delivered on a daily basis. The baseline characteristics of the patients in the two treatment groups were similar. The primary study outcome--survival until discharge from the ICU or survival for 30 days, whichever was earlier--did not significantly differ between the two groups: 70% after CVVHDF and 87% after S-HDF. The hospital-survival rate after CVVHDF was 63% and that after S-HDF was 83% (P < 0.05). The number of patients who showed renal recovery at the time of discharge from the ICU and the hospital and the duration of the ICU stay significantly differed between the two treatments (P < 0.05). Although there was no significant difference between the mean number of treatments performed per patient, the mean duration of daily treatment in the S-HDF group was 6.5 +/- 1.0 h, which was significantly shorter. Although the total convective volumes--the sum of the replacement-fluid and fluid-removal volumes--did not differ significantly, the dialysate-flow rate was higher in the S-HDF group. Our results suggest that in comparison with conventional continuous RRT, including high-dose CVVHDF, more intensive renal support in the form of postdilution S-HDF will decrease the mortality and accelerate renal recovery in critically ill patients with AKI.

A case report of acute renal failure and fulminant hepatitis associated with edaravone administration in a cerebral infarction patient.

A 60-year-old male with cerebral infarction was admitted to our hospital and treated with edaravone. On day 12 of hospitalization, he suddenly lost consciousness and went into shock. Based on the laboratory findings, acute renal failure (ARF), fulminant hepatitis, and disseminated intravascular coagulation (DIC) were diagnosed. We immediately initiated continuous hemodiafiltration for three days and performed three sessions of plasma exchange. Following this, a gradual improvement was observed in the patient's general condition and laboratory values. On day 17 of hospitalization, intermittent hemodialysis (HD) was initiated. On day 20 of hospitalization, his renal function started to improve with an increase in urine volume. HD was successfully discontinued on the same day. Although the drug lymphocyte stimulation test for edaravone was negative, edaravone-induced fulminant hepatitis was suggested based on liver biopsy findings. We present a case of ARF, fulminant hepatitis, and DIC due to edaravone administration that was successfully treated with blood purification techniques. Since the use of edaravone treatment is expected to increase in the future, it is essential that clinicians consider the potential adverse effects of this treatment. It is suggested that blood purification is effective in inducing remission in patients with complications due to edaravone treatment.

Plasma insulin is removed by hemodialysis: evaluation of the relation between plasma insulin and glucose by using a dialysate with or without glucose.

The aim of the present study was to evaluate the alteration in plasma immunoreactive insulin (IRI) and glucose concentrations due to hemodialysis (HD) treatment by using a dialysate with or without glucose in HD patients. We divided the patients into three groups: non-diabetic patients (n-DM group), well-controlled diabetic patients (HbA(1c) <7.0% [w-DM group]), and poorly-controlled diabetic patients (HbA(1c) > or = 7.0% [p-DM group]). Using a dialysate with a glucose concentration of 100 mg/dL (glu(+)-dialysate) and a glucose-free dialysate (glu(-)-dialysate), we studied the daily profiles of plasma glucose in the three groups. We measured the levels of plasma glucose and IRI at three time points (predialysis and 2 h and 4 h after the initiation of dialysis) at pre(A) and postdialyzer (V) sites in HD patients. There was a significant increase in the daily profiles of the plasma glucose level from the time before dinner until bedtime in both the w-DM and p-DM groups, when comparing the values on an HD day with those on a non-HD day. In the p-DM group, the use of the glu(-)-dialysate resulted in a significant hyperglycemia in the evening hours when compared with the use of the glu(+)-dialysate. In the DM group, the use of the glu(+)-dialysate resulted in a significant decrease in the plasma glucose and IRI levels during HD. However, in the n-DM group, there was no difference in the plasma glucose levels during HD. On the other hand, the use of a glucose-free dialysate led to a significant decrease in the plasma glucose and IRI levels during HD in all groups. The plasma IRI levels decreased significantly between the A and V sites at each point in all groups irrespective of the glucose concentration of the dialysate. The present study confirmed that the concentration of not only glucose but also IRI had decreased during the passage of the plasma through the dialyzer. In HD patients with diabetes, the glucose content of the hemodialysis solution plays an important role in preventing acute hypoglycemia and hyperglycemia on HD days.

Evaluation of the hemodialysis-induced changes in plasma glucose and insulin concentrations in diabetic patients: comparison between the hemodialysis and non-hemodialysis days.

Often, well-controlled plasma glucose levels but high hemoglobin A(1c) levels have been observed at prehemodialysis in diabetic patients. The present study aimed to evaluate this difference between fasting glucose and hemoglobin A(1c) levels. We investigated hemodialysis-induced alterations in the plasma glucose and insulin levels. Based on their glycemic control level at inclusion, subjects were divided into poor control (hemoglobin A(1c)> or =7.0%; n = 8) and good control groups (hemoglobin A(1c) <7.0%; n = 8). We measured their plasma glucose and immunoreactive insulin levels at arterial and venous sites at three time points (predialysis, 2 h and 4 h after starting dialysis); we also studied their daily plasma glucose profiles. In both the groups, the V-site plasma glucose and immunoreactive insulin levels were significantly decreased compared to the A-site levels at each time point. The A-site plasma immunoreactive insulin levels 4 h after dialysis were significantly decreased compared to the levels 2 h after dialysis. Comparison between hemodialysis and non-hemodialysis days revealed that the plasma glucose levels decreased significantly during hemodialysis and significantly increased between predinner and bedtime in the poor control group. The present study confirmed that hemodialysis decreased the plasma glucose and immunoreactive insulin levels. In the poor control group, hyperglycemia appeared posthemodialysis; this was attributed partly to the hemodialysis-induced decrease in the plasma immunoreactive insulin levels. These results suggest that although diet therapy has been effective in diabetic hemodialysis patients, hemodialysis caused hyperglycemia by absolute or relative plasma immunoreactive insulin deficiency.

[Drug-induced edema].

It is well known that there are many drugs which induce edema. Drug-induced edema can be divided into three types by the mechanism as follows, 1) sodium overload, 2) renal dysfunction and 3) hyperpermeability of blood vessel. In the category of sodium overload, edema is induced by much fluid replacement and antibiotics which contain large amount of sodium and sodium bicarbonate. As the category of renal dysfunction, NSAIDs, antihypertensive drugs, anticancer drugs and so on induce edema in patients with renal dysfunction. In the category of hyperpermeability of blood vessel, edema is induced by calcium antagonist, insuline and so on. In order to diagnose drug-induced edema early, it is important that we interrupt or reduce the quantity of suspicious drug.

Endotoxin removal by direct hemoperfusion with an adsorbent column using polymyxin B-immobilized fiber ameliorates systemic circulatory disturbance in patients with septic shock.

Direct hemoperfusion (DHP) with an adsorbent column using polymyxin B-immobilized fiber (PMX-F) has been shown to improve the state of shock in patients with septic shock. However, no evidence has been presented for a direct link between endotoxin removal by DHP with PMX-F and improvement in septic shock. We retrospectively analyzed clinical profiles of 24 patients with septic shock (16 patients, gram-negative; 8 patients, non-gram-negative septic shock) who underwent DHP with PMX-F. Patients with gram-negative septic shock were characterized by hyperdynamic circulation. DHP with PMX-F reduced blood endotoxin concentrations and ameliorated shock, with an improvement in hyperdynamic circulation in patients with gram-negative septic shock. Mean arterial pressure also was elevated after therapy in patients with non-gram-negative septic shock, but systemic hemodynamics were unaffected. Regardless of the causative microorganism, patients with endotoxemia (blood endotoxin level > 10 pg/mL) showed hyperdynamic shock, and DHP with PMX-F reduced blood endotoxin levels and ameliorated hyperdynamic circulation, whereas patients without endotoxemia showed features of shock without hyperdynamic circulation, and DHP with PMX-F ameliorated shock without affecting cardiac performance. In patients with gram-negative septic shock, blood endotoxin concentration correlated positively with cardiac output and negatively with systemic vascular resistance before DHP therapy. Reduction in blood endotoxin concentration by DHP therapy positively correlated with the reduction in cardiac output. Our findings indicate that the improvement in hyperdynamic circulation was related directly to endotoxin removal by the PMX-F column, and endotoxin has an important role in the development of hyperdynamic circulation in patients with gram-negative septic shock.

Expression of type-1 plasminogen activator inhibitor in the kidney of diabetic rat models.

INTRODUCTION: Intrarenal coagulation and fibrinolysis are thought to be involved in the pathogenesis of diabetic nephropathy. However, gene expression of fibrinolytic factors in diabetic nephropathy has not been clearly defined. Therefore we determined the gene expression of fibrinolytic factors in the kidneys of diabetic rats. MATERIALS AND METHODS: As a model of type1 diabetes male Sprague-Dawley rats were used. They were divided into three groups: control, streptozotocin (STZ)-induced diabetic, and insulin-treated diabetic. Otsuka Long-Evans Tokushima Fatty (OLETF) rats were used as a model of type 2 diabetes; and Long-Evans Tokushima Otsuka (LETO) rats, as the control. Renal gene expressions of type-1 plasminogen activator inhibitor (PAI-1), tissue-type PA (tPA), and urokinase-type PA (uPA) were examined by real-time PCR. Localization of PAI-1 mRNA was investigated by in situ hybridization. RESULTS: Renal PAI-1 mRNA levels (versus control) were increased by 60-80% in STZ-induced diabetic rats (10 days or 3 weeks post STZ injection); and insulin treatment reduced this increased expression to the control level. In OLETF rats (38 weeks old), the renal PAI-1 mRNA level was 2.5-fold higher than that in age-matched LETO rats. Both tPA and uPA mRNA levels were significantly lower than those in LETO rats. PAI-1 mRNA was observed in intraglomerular cells and tubular epithelial cells of both models. CONCLUSIONS: Renal PAI-1 gene expression is up-regulated in both type 1 and type 2 diabetic rats, and changes in gene expressions of fibrinolytic factors may play important roles in the development and pathogenesis of diabetic nephropathy.

Serum interleukin-18 binding protein increases with behavior different from IL-18 in patients with diabetic nephropathy.

We investigated alterations between serum interleukin 18 (IL-18) and IL-18 binding protein (18BP) in T2DM patients. 18 BP began to increase after IL-18 increased and reached a threshold, in which case kidney dysfunction would have developed. These data indicate that 18BP might express glomerular dysfunction more closely than IL-18.

Current status of blood purification in critical care in Japan.

In order to clarify the present status of blood purification therapy (BPT) in critical care in Japan, questionnaires investigating all the patients who were treated with BPT in 2005 were distributed. The number of patients who received BPT was 9,795, and the number of BPT performed was 11,623. The number and types of BPT treatment given are: continuous hemodiafiltration (CHDF)/hemofiltration (HDF) 5,443 (50.3%); continuous hemofiltration (CHF) 812 (7.5%); continuous hemodialysis (CHD) 877 (8.1%); simple plasma exchange 898 (8.3%); direct hemoperfusion (DHP) with polymyxin-B-coated textile (PMX-DHP) 1,625 (15.0%); DHP with activated carbon (AC-DHP) 129 (1.2%). The survival rates of patients with continuous therapies (CHDF, CHF, CHD) were as follows: multiple organ failure with CHDF 35%; sepsis with CHDF 65%; acute hepatic failure with CHDF 50%; acute renal failure with CHDF 66%; acute drug intoxication with AC-DHP 79%. In conclusion, continuous therapies such as CHDF, CHF and CHD were the most popular modes (> 65%) of BPT in Japan. The worst survival rate among diseases in critical care was found in multiple organ failure patients. The best survival rate was in those who suffered from acute renal failure.

Clinical evaluation of pneumonia-associated rhabdomyolysis with acute renal failure.

This study aims to evaluate the clinical features, diagnosis, and treatment efficacy in patients with pneumonia-associated rhabdomyolysis and acute renal failure. The subjects included six patients who had presented with rhabdomyolysis and acute renal failure due to bacterial or viral pneumonia on admission to our university hospital and the Yokohama Social Insurance Central Hospital between 2004 and 2005. The causative organisms were identified as Legionella pneumophila (N = 1), Staphylococcus epidermidis (N = 2), Staphylococcus aureus (N = 1), and Unknown (N = 2). For anuric or oliguric patients (N = 4), a blood purification therapy was performed, while conservative therapy was administered to those with a normal urine volume (N = 2). The patient suffering from L. pneumophila pneumonia did not survive, while the other patients regained full kidney function. It is important to identify, evaluate, and treat patients with bacterial or viral pneumonia-associated rhabdomyolysis and acute renal failure.