Kazo Kaizu

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.

Clinical study of influenza-associated rhabdomyolysis with acute renal failure.

AIMS Influenza-associated rhabdomyolysis induces renal failure with a fatal outcome. The aim of this study is to evaluate the clinical features, diagnosis, and treatment efficacy of influenza-associated rhabdomyolysis patients with acute renal failure (ARF). MATERIALS AND METHODS The subjects included 6 patients who had presented with rhabdomyolysis and ARF due to influenza infection on admission to our university hospital and its 2 affiliated hospitals between January 2002 and February 2004. We retrospectively examined the cases. RESULTS All the patients (n = 6) were males, and none of them had received an influenza vaccine. The viruses were identified as influenza A (n = 5) and B (n = 1). Muscular weakness was observed in many cases (n = 5), whereas pain or tenderness was observed in only 1 case (n = 1). For anuric or oliguric patients (n = 4), blood purification therapy was performed, while for patients in whom the urine volume was normal (n = 2), conservative therapy was administered. CONCLUSION Careful medical attention is necessary when patients have muscle pain and weakness. Early recognition of rhabdomyolysis allows prompt institution of an appropriate therapy that includes blood purification and may minimize the renal dysfunction associated with this disorder.

Best Practice for Diabetic Patients on Hemodialysis 2012

1. Predialysis casual plasma glucose and glycated albumin (GA) levels are recommended as indicators for glycemic control. 2. The hemoglobin A1c (HbA1c) level might be used only as reference, because HbA1c level decreases in the presence of anemia or erythropoiesis-stimulating agents (ESAs) and may not accurately represent glycemic control in hemodialysis patients. 3. Tentative targets for glycemic control: predialysis casual plasma glucose levels (or 2-h postprandial plasma glucose levels) <180– 200 mg/dL and GA levels <20.0% are recommended for hemodialysis patients. GA levels <24.0% are suggested for hemodialysis patients with a history of cardiovascular events and who have hypoglycemic episodes.Further studies are required to definitively determine target values. 4. In glycemic control, multiple indicators, including predialysis casual plasma glucose and GA levels, should be comprehensively evaluated to reduce the risk of hypoglycemia and improve the prognosis of patients.

Plasma Insulin is Removed by Hemodialysis: Evaluation of the Relation Between Plasma Insulin and Glucose by Using a Dialysate With or Without Glucose

Abstract:  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 (HbA1c <7.0% [w‐DM group]), and poorly‐controlled diabetic patients (HbA1c≥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.

Combination therapy of pioglitazone with voglibose improves glycemic control safely and rapidly in Japanese type 2-diabetic patients on hemodialysis.

AIMS Unfortunately, clinicians are diagnosing a growing number of patients on hemodialysis (HD) with insulin-resistant, Type 2 diabetes in Japan. While alpha-glucosidase inhibitors (alpha-GI) such as oral antidiabetic agents are indicated for Japanese diabetics on HD, pioglitazone and other PPARgamma agonists are now contraindicated. No prospective study has evaluated the use of thiazolidinediones in diabetics with end-stage renal disease (ESRD) in combination with alpha-GI. In this study we evaluated the efficacy and safety of pioglitazone in Japanese diabetics on HD. METHODS An open-label randomized study was performed on 31 Type 2 diabetics on HD with unstable glycemic control receiving constant doses of voglibose. The patients were randomly assigned to two groups: a combination therapy group (pioglitazone group) administered pioglitazone (fixed dose 30 mg) plus voglibose, and a monotherapy group (control group) administered voglibose alone. The efficacy of the treatments was determined by monitoring glycemic control (plasma glucose and HbA1c) and insulin resistance. Insulin resistance was assessed using the homeostasis model assessment for insulin resistance (HOMA-R). Safety and tolerance were determined by monitoring clinical and laboratory parameters. RESULTS The pioglitazone was effective in reducing plasma glucose and HbA1c from the baseline levels from Week 4 onward. It was also effective in reducing triglycerides. HOMA-R decreased significantly at 4 weeks in the pioglitazone group, and the decrease continued up to the last measurement at Week 12. Systolic and diastolic blood pressures at 4 weeks were statistically lower in the pioglitazone group than in the control group. No serious adverse effects such as hypoglycemia, liver impairment or rhabdomyolysis were observed in any of the patients. CONCLUSIONS Pioglitazone was safe and effective as a treatment for diabetics on dialysis therapy. The 30 mg daily dose of pioglitazone was sufficient for Japanese HD patients, obese and nonobese alike. The combination therapy of pioglitazone with voglibose will add to the list of first-line drug treatments for glycemic control in uremic Type 2 diabetes.

Renal hemodynamics in Otsuka Long-Evans Tokushima fatty rat, a model rat of spontaneous non-insulin-dependent diabetes mellitus with obesity

Renal hemodynamic features in obese non-insulin-dependent diabetic rats remain unknown. We investigated renal hemodynamic and morphologic changes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats at the age of 5 and 10 months compared with age-matched lean nondiabetic control rats (LETO). OLETF rats showed obesity compared with age-matched LETO rats. Hyperglycemia was mild in 5-month-old OLETF rats and moderate in 10-month-old OLETF rats. The absolute value for glomerular filtration rate (GFR) was significantly higher in OLETF rats than in age-matched LETO rats at the age of 5 and 10 months. Ten-month-old OLETF rats had significantly higher absolute values for renal plasma flow (RPF) than age-matched LETO rats but not 5-month-old OLETF rats. Stepwise multiple regression analysis revealed that body weight was a powerful determinant of GFR and RPF. When factored for body weight, no difference in GFR was demonstrated between 5-month-old OLETF and LETO rats, whereas 10-month-old OLETF rats still had significantly higher GFR and RPF than age-matched LETO rats. Renal hypertrophy was demonstrated in both 5- and 10-month-old OLETF rats even when factored for body weight. Glomerular volume was significantly increased in 10-month-old OLETF rats, but the ratio of glomerular volume to body weight was not different among the groups. Both absolute value for glomerular capillary length free from mesangial area and the value factored for glomerular area were significantly longer in OLETF rats than in age-matched LETO rats. Mesangial matrix expansion was remarkable in 10-month-old OLETF rats, and the glomerular sclerosis index was significantly higher in 10-month-old OLETF rats than in age-matched LETO rats. Stepwise multiple regression analysis revealed that body weight, hemoglobin A1c, and hypertriglyceridemia were powerful determinants for kidney weight and glomerular volume. These data suggest that renal hyperfiltration and hypertrophy observed in 10-month-old OLETF rats are related to diabetic metabolic disorders and that obesity-related conditions may be involved in the renal hemodynamic and morphologic features in OLETF rats.

Efficacy of pioglitazone on type 2 diabetic patients with hemodialysis

AIMS Unfortunately, growing number of type 2 diabetic hemodialysis (HD) patients with insulin resistance are now being diagnosed in Japan. Worse still, PPARgammaagonists such as pioglitazone are now contraindicated in diabetic HD patients in Japan. In this study we evaluated the efficacy of pioglitazone in diabetics on HD. METHODS Following a 12-week baseline period, we enrolled a study population of poorly controlled diabetic HD patients who had mean hemoglobin A1c (HbA1c) levels greater than 6.5% at baseline and who were not receiving insulin injection therapy. The patients were administered pioglitazone 15mg daily with their morning meal for the first 4 weeks. Subsequently, the doses were titrated by dose-doubling to a maximum of 30mg/day if no adverse effects appeared. The efficacy was determined by monitoring glycemic control (plasma glucose and HbA1c), and insulin resistance (plasma immunoreactive insulin (IRI) and homeostasis model assessment for insulin resistance (HOMA-R)). Safety and tolerance were determined by monitoring clinical and laboratory parameters. RESULTS Pioglitazone was effective in reducing plasma glucose and HbA1c from the baseline levels from week 4 after the commencement of treatment. The agent was also effective in reducing triglycerides. Plasma IRI and HOMA-R, two parameters of insulin resistance, decreased significantly at 4 weeks, and the decreases continued for 24 weeks. Systolic and diastolic blood pressures were statistically lower at 8 weeks. No serious adverse effects such as hypoglycemia, liver impairment, or rhabdomyolysis were observed in any of the patients. CONCLUSIONS Pioglitazone was effective in the treatment of diabetics on dialysis therapy. Pioglitazone might have the potential to reduce the number of type 2 diabetics on HD who ultimately require insulin injection therapy.

Evaluation of the Hemodialysis‐induced Changes in Plasma Glucose and Insulin Concentrations in Diabetic Patients: Comparison Between the Hemodialysis and Non‐hemodialysis Days

Abstract:  Often, well‐controlled plasma glucose levels but high hemoglobin A1c levels have been observed at prehemodialysis in diabetic patients. The present study aimed to evaluate this difference between fasting glucose and hemoglobin A1c 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 A1c≥7.0%; n = 8) and good control groups (hemoglobin A1c <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.

A Case Report of Acute Renal Failure and Fulminant Hepatitis Associated With Edaravone Administration in a Cerebral Infarction Patient

Abstract:  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 patients 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.

The influence of hemodialysis membranes on the plasma insulin level of diabetic patients on maintenance hemodialysis.

AIM The aim of the present study was to evaluate the alteration in plasma immunoreactive insulin (IRI) concentrations due to hemodialysis (HD) treatment by using three types of membranes in diabetic HD patients. METHOD We recruited 20 outpatients on maintenance HD with diabetes for this crossover study. HD was performed using membranes made of cellulose triacetate (CTA), polyester-polymer alloy (PEPA), and polysulphone (PS). These membranes were used for 2 weeks (6 HD sessions) in each patient in a randomized order decided by drawing lots. Blood samples were obtained at the beginning and end of the HD session from the blood tubing at the arterial (A) site. At 60 min after the initiation of dialysis, blood samples were obtained from the blood tubing at both the A and venous (V) sites of the dialyzer. RESULTS The plasma IRI levels decreased significantly at the sites an hour after initiating HD in all membranes. The clearance of IRI was significantly higher in the case of the PS membrane when compared with the CTA and PEPA membranes. CONCLUSIONS It was concluded that plasma insulin is cleared by HD, and the rate differs for each membrane. Plasma insulin clearance with the PS membrane is higher than that with the PEPA and CTA membranes.