Mass spectrometry-based proteomic analysis of proteins adsorbed by hexadecyl-immobilized cellulose bead column for the treatment of dialysis-related amyloidosis.

Background: Dialysis-related amyloidosis (DRA) is a severe complication in end-stage kidney disease (ESKD) patients undergoing long-term dialysis treatment, characterized by the deposition of β-microglobulin-related amyloids (Aβ2M amyloid). To inhibit DRA progression, hexadecyl-immobilized cellulose bead (HICB) columns are employed to adsorb circulating β-microglobulin (β2M). However, it is possible that the HICB also adsorbs other molecules involved in amyloidogenesis.

Difelikefalin for Hemodialysis Patients with Pruritus in Japan.

BACKGROUND: Difelikefalin, a peripherally specific selective agonist of kappa opioid receptors, has been approved for the treatment of pruritus in hemodialysis patients in the United States. However, there is limited evidence for postdialysis intravenous use in non-U.S.

Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis.

Dialysis-related amyloidosis (DRA), a serious complication among long-term hemodialysis patients, is caused by amyloid fibrils of β2-microglobulin (β2m). Although high serum β2m levels and a long dialysis vintage are the primary and secondary risk factors for the onset of DRA, respectively, patients with these do not always develop DRA, indicating that there are additional risk factors. To clarify these unknown factors, we investigate the effects of human sera on β2m amyloid fibril formation, revealing that sera markedly inhibit amyloid fibril formation.

Efficacy and Safety of Difelikefalin in Japanese Patients With Moderate to Severe Pruritus Receiving Hemodialysis: A Randomized Clinical Trial.

Importance: Patients with pruritus receiving hemodialysis frequently experience oppressive physical and psychiatric symptoms that directly affect their quality of life and increase mortality. However, treatment options are limited.

Objective: To determine the clinically recommended dose of difelikefalin, a κ-opioid receptor agonist, based on the efficacy, dose response, safety, and pharmacokinetics.

Adsorption of Protein-Bound Uremic Toxins Using Activated Carbon through Direct Hemoperfusion in vitro.

Background/aims: Accumulation of protein-bound uremic toxins (PBUTs) is associated with mortality due to various systemic disorders in patients with chronic kidney disease (CKD), especially in those undergoing dialysis treatment. The clinical outcomes of such patients could be improved by removing sufficient amounts of PBUTs; however, conventional dialysis lacks this ability. We examined the efficacy of activated carbon in adsorbing circulating PBUTs through direct hemoperfusion (DHP) in vitro.

Indoxyl Sulfate Promotes Macrophage IL-1β Production by Activating Aryl Hydrocarbon Receptor/NF-κ/MAPK Cascades, but the NLRP3 inflammasome Was Not Activated.

In chronic kidney disease (CKD) patients, accumulation of uremic toxins is associated with cardiovascular risk and mortality. One of the hallmarks of kidney disease-related cardiovascular disease is intravascular macrophage inflammation, but the mechanism of the reaction with these toxins is not completely understood. Macrophages differentiated from THP-1 cells were exposed to indoxyl sulfate (IS), a representative uremic toxin, and changes in inflammatory cytokine production and intracellular signaling molecules including interleukin (IL)-1, aryl hydrocarbon receptor (AhR), nuclear factor (NF)-κ, and mitogen-activated protein kinase (MAPK) cascades as well as the NLRP3 inflammasome were quantified by real-time PCR, Western blot analysis, and enzyme-linked immunosorbent assay.

Adsorption of Protein-Bound Uremic Toxins Through Direct Hemoperfusion With Hexadecyl-Immobilized Cellulose Beads in Patients Undergoing Hemodialysis.

An accumulation of protein-bound uremic toxins (PBUTs) is one of major reasons for development of uremia-related complications. We examined the PBUT removal ability of a hexadecyl-immobilized cellulose bead (HICB)-containing column for patients undergoing hemodialysis. Adsorption of indoxyl sulfate (IS), a representative PBUT, to HICBs was examined in vitro.

Effect of Predialysis Recombinant Human Erythropoietin on Early Survival After Hemodialysis Initiation in Patients With Chronic Kidney Disease: Co-JET Study.

Progression of anemia in patients with chronic kidney disease (CKD) is associated with an increased risk of death and hospitalization. It is not sufficiently clear whether treating renal anemia with recombinant human erythropoietin (rHuEPO) has a beneficial effect on early survival after hemodialysis (HD) initiation in patients with CKD. The study was an open-label multicenter retrospective cohort study to evaluate the relationship between rHuEPO treatment and early survival after HD initiation in patients with CKD.

Orally active prostacyclin analogue beraprost sodium in patients with chronic kidney disease: a randomized, double-blind, placebo-controlled, phase II dose finding trial.

Background: Evidence increasingly points to the importance of chronic hypoxia in the tubulointerstitium as a final common pathway to end-stage renal disease (ESRD). Beraprost sodium (BPS) is an orally active prostacyclin (PGI2) analogue demonstrating prevention of the progression of chronic kidney disease (CKD) in various animal models by maintaining renal blood flow and attenuating renal ischemic condition.

Methods: This multicenter, randomized, double-blind, placebo-controlled, phase II trial was designed to determine the recommended dose of the sustained-release form of BPS (TRK-100STP 120 μg/day or 240 μg/day) in Japanese patients with CKD.

Depression's influence on the Asthma Control Test, Japanese version.

Background: Depression has been linked to poorer asthma control in asthmatic patients. Although the Japanese version of the Asthma Control Test (ACT-J) is frequently used as a simple, practical evaluation tool in clinical care settings in Japan, knowledge regarding its efficacy for assessing asthma control in asthmatic patients with depression is limited. Thus, we retrospectively investigated cut-off values of the ACT-J for well-controlled asthma, and explored depression's influence on the test with a questionnaire survey.

Impacts of recombinant human erythropoietin treatment during predialysis periods on the progression of chronic kidney disease in a large-scale cohort study (Co-JET study).

The effect of recombinant human erythropoietin (rHuEPO) treatment on the progression of chronic kidney disease (CKD) has not been fully evaluated in Japan. We therefore retrospectively evaluated this in a sub-cohort of a prospective multicenter study to investigate optimal hemoglobin (Hb) level of CKD patients on hemodialysis (HD) treated with rHuEPO; Japan Erythropoietin Treatment Study for Target Hb and Survival (JET study). Effect of rHuEPO treatment during predialysis period to delay initiation of HD was retrospectively assessed in 2434 patients from the JET study comparing groups with and without rHuEPO treatment.

Low hemoglobin levels and hypo-responsiveness to erythropoiesis-stimulating agent associated with poor survival in incident Japanese hemodialysis patients.

Although erythropoiesis-stimulating agents (ESAs) are effective at treating anemia, the association between hemoglobin (Hb) levels and survival is still unclear, especially for the incident Japanese hemodialysis (HD) population. The Japan Erythropoietin Treatment (JET) Study is an open multi-center, prospective, observational study designed to evaluate the relationship between the maintenance of Hb levels and new HD patient prognosis after the first administration of epoetin beta. Landmark analyses were performed to examine the relationship between Hb levels at 6 months and survival.

Analysis of the influenza A (H1N1) 2009 pandemic infection in Japanese asthmatic patients: using a questionnaire-based survey.

Background: Influenza infection is known to be an exacerbating factor in the control of asthma, therfore its prevention is critical in managing asthma. The aim of this study was to investigate the influenza A H1N1 2009 pandemic virus (H1N1 pdm09) infection in adult asthmatic patients.

Methods: Data were obtained from a questionnaire-based survey of asthmatic patients conducted from September to October 2010 in Niigata Prefecture.

The Asthma Control Test, Japanese version (ACT-J) as a predictor of Global Initiative for Asthma (GINA) guideline-defined asthma control: analysis of a questionnaire-based survey.

Background: The 2006 Global Initiative for Asthma (GINA 2006) guidelines emphasize the importance of evaluating the control rather than the severity of asthma. The Asthma Control Test (ACT) is well known to be an excellent tool for evaluating asthma control in the clinical setting. This study aimed to evaluate the ACT, Japanese version (ACT-J) as a predictor of asthma control as defined by the GINA 2006 guidelines in actual clinical practice.

Survey of the effects of a column for adsorption of β2-microglobulin in patients with dialysis-related amyloidosis in Japan.

Dialysis-related amyloidosis is a serious complication of long-term hemodialysis. Its pathogenic mechanism involves accumulation of β2-microglobulin in the blood, which then forms amyloid fibrils and is deposited in tissues, leading to inflammation and activation of osteoclasts. Lixelle, a direct hemoperfusion column for adsorption of β2-microglobulin, has been available since 1996 to treat dialysis-related amyloidosis in Japan.

The Asthma Control Test, Japanese Version (ACT-J) as a Predictor of Global Initiative for Asthma (GINA) Guideline-Defined Asthma Control: Analysis of a Questionnaire-Based Survey.

Background: The 2006 Global Initiative for Asthma (GINA 2006) guidelines emphasize the importance of evaluating the control rather than the severity of asthma. The Asthma Control Test (ACT) is well known to be an excellent tool for evaluating asthma control in the clinical setting. This study aimed to evaluate the ACT, Japanese version (ACT-J) as a predictor of asthma control as defined by the GINA 2006 guidelines in actual clinical practice.

High target hemoglobin with erythropoiesis-stimulating agents has advantages in the renal function of non-dialysis chronic kidney disease patients.

We investigated the long-term effects of maintaining high hemoglobin (Hb) on renal function in patients with chronic kidney disease not on dialysis. Subjects (Hb < 10 g/dL and serum creatinine (Cr) 2-6 mg/dL) were randomized to either a high Hb group (N = 161, 11.0 ≤ Hb < 13.

Efficacy of using the Japanese version of the asthma control test for determing the level of asthma control in clinical settings.

Background: The Asthma Control Test (ACT) is frequently used for the evaluation of asthma control in clinical care setting because it does not require the use of pulmonary function tests, which can be difficult for general practitioners to use. However, few large-scale studies have investigated the efficacy of the Japanese version ACT (J-ACT) in actual use during clinical care.

Methods: The aim of this study was to analyze the efficacy of the J-ACT in a clinical care setting.

Influence of underweight on asthma control.

Background: Although the association between asthma control and body mass index (BMI) has been thoroughly investigated, most of this work has focused on the influence on asthma incidence or the effect of obesity on asthma control. To date, there have been no published studies on the influence of underweight on asthma control.

Methods: The aim of this study was to investigate the influence of underweight, as defined by the Japan Society for the Study of Obesity (JASSO), on asthma control in Japanese asthmatic patients.

Analysis of depression in asthmatic patients using the Japanese version of Patient Health Questionnaire-9.

Background: Previous studies show that depression plays an important role in asthma. However, the association between asthma control and severity, and depression is inconclusive.

Methods: To investigate the association between asthma control and severity, and depression, we assessed differences in asthma control and asthma severity between groups with various grades of depressive state as defined by the PHQ-9 score using data from the Japanese version of Patient Health Questionnaire-9 (J-PHQ-9) and a questionnaire survey including the Asthma Control Test (ACT).

Significance of urinary full-length and ectodomain forms of megalin in patients with type 2 diabetes.

Objective: Megalin, an endocytic receptor in proximal tubule cells, is involved in the mechanisms of albuminuria in diabetic nephropathy (DN). To develop efficient novel biomarkers associated with the pathogenesis of DN, we investigated urinary megalin excretion in type 2 diabetes.

Research Design And Methods: Sandwich enzyme-linked immunosorbent assay systems were established with monoclonal antibodies against the NH(2) (amino [A]-megalin assay) and COOH (C-megalin assay) termini of megalin to analyze urinary forms of megalin in 68 patients with type 2 diabetes.

Hypogammaglobulinemic patient with polyarthritis mimicking rheumatoid arthritis finally diagnosed as septic arthritis caused by Mycoplasma hominis.

Hypogammaglobulinemia is a reduction or absence of immunoglobulin, which may be congenital or associated with immunosuppressive therapy. In addition to infectious diseases, autoimmune diseases have also been reported in patients with hypogammaglobulinemia. A 26-year-old man with hypogammaglobulinemia had multiple joint pain and swelling with erosive changes in the proximal interphalangeal joint of the right middle finger on X-ray film, mimicking rheumatoid arthritis (RA).

Integrin α1/β1 and α2/β1 as a receptor for IgA1 in human glomerular mesangial cells in IgA nephropathy.

IgA nephropathy (IgAN) is characterized by mesangial deposition of IgA1 and galactose-deficient IgA1 is expected to play a pathogenic role. However, the identity of the receptor for IgA1 is still controversial. Hence, the aim of this study was to explore the receptor for galactose-deficient IgA1.

Positive outcomes of high hemoglobin target in patients with chronic kidney disease not on dialysis: a randomized controlled study.

Correcting anemia in patients with chronic kidney disease (CKD) to higher hemoglobin (Hb) levels may be associated with increased risk. No optimal target for Hb has been established. This controlled study examined 321 patients with CKD who were not on dialysis, had a Hb level of <10g/dL, and a serum creatinine of 2.