Rationale and trial design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON).

Background: Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic triterpenoid that reduces oxidative stress and inflammation through Nrf2 activation and inhibition of NF-κB was previously shown to increase estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes mellitus. To date, no antioxidant or anti-inflammatory therapy has proved successful at slowing the progression of CKD.

Clinical correlates of ambulatory BP monitoring among patients with CKD.

Background And Objectives: Ambulatory BP monitoring (ABPM) allows a better risk stratification than office BP in hypertensive patients. However, the clinical relevance of ABPM has not been extensively investigated in the CKD population.

Design, Setting, Participants, & Measurements: Within the Chronic Kidney Disease Japan Cohort study, 2977 patients enrolled (62% men, aged 60.

Risk factors for increased left ventricular hypertrophy in patients with chronic kidney disease.

Background: Although left ventricular hypertrophy (LVH) has been established as a predictor of cardiovascular events in chronic kidney disease (CKD), the relationship between the prevalence of LVH and CKD stage during the predialysis period has not been fully examined.

Methods: We measured left ventricular mass index (LVMI) in a cross-sectional cohort of participants in the Chronic Kidney Disease Japan Cohort (CKD-JAC) study in order to identify factors that are associated with increased LVMI in patients with stage 3-5 CKD. LVH was defined as LVMI>125 g/m2 in male patients and >110 g/m2 in female patients.

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.

Long- and short-term treatment with imatinib attenuates the development of chronic kidney disease in experimental anti-glomerular basement membrane nephritis.

Background: Imatinib is a selective tyrosine kinase inhibitor that can block platelet-derived growth factor (PDGF) receptor activity. Imatinib is also known as an anti-inflammatory agent. We examined the therapeutic effects of long- or short-term imatinib treatment in Wistar-Kyoto (WKY) rats with established anti-glomerular basement membrane (GBM) nephritis.

Effects of anemia correction by erythropoiesis-stimulating agents on cardiovascular function in non-dialysis patients with chronic kidney disease.

Anemia is a significant risk factor for patients with chronic kidney disease (CKD). Here, we investigated the effects of anemia correction on cardiac functions in CKD patients. Pre-dialysis CKD patients (n = 171) without known risk factors for cardiovascular disease (CVD) other than CKD with hemoglobin (Hb) concentrations < 10.

Effect of renal impairment on the pharmacokinetics of memantine.

The effect of renal impairment on the pharmacokinetics of a single oral dose of memantine (10 mg) was determined in Japanese subjects. Subjects were assigned to four groups based on baseline creatinine clearance (CL(CR)): normal renal function (> 80 mL/min, n = 6), and mild (50 to ≤ 80 mL/min, n = 6), moderate (30 to < 50 mL/min, n = 6), and severe renal impairment (5 to < 30 mL/min, n = 7). Mean memantine maximum plasma concentration (C(max)) was similar in the groups (12.

Prescription patterns and mineral metabolism abnormalities in the cinacalcet era: results from the MBD-5D study.

Background And Objectives: Prescription patterns for hemodialysis patients with secondary hyperparathyroidism have varied widely since market introduction of cinacalcet. This study examined associations between prescription patterns and subsequent laboratory values.

Design, Setting, Participants, & Measurements: Using a Mineral and Bone Disorder Outcomes Study for Japanese CKD Stage 5D Patients subcohort, 1716 prevalent hemodialysis patients (4048 sets for repeated measures between January 2008 and July 2009) with an intact parathyroid hormone (iPTH) level >180 pg/ml who used intravenous vitamin D receptor activator (VDRA) without cinacalcet were selected.

Understanding measurements of vitality in patients with chronic kidney disease: connecting a quality-of-life scale to daily activities.

Background: Many patients with chronic kidney disease (CKD) suffer from fatigue caused by anemia, but that anemia can be reversed. Successful treatment can be measured as a decrease in fatigue and an increase in energy or vitality, particularly on the vitality (VT) subscale of the SF-36. Changes in VT scores are most commonly interpreted in terms of minimally important differences or standardized effect sizes, but neither a minimally important difference nor a standardized effect size provides information about how patients' activities are affected.

Blood pressure levels and mortality risk among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study.

KDOQI practice guidelines recommend predialysis blood pressure <140/90 mm Hg; however, most prior studies had found elevated mortality with low, not high, systolic blood pressure. This is possibly due to unmeasured confounders affecting systolic blood pressure and mortality. To lessen this bias, we analyzed 24,525 patients by Cox regression models adjusted for patient and facility characteristics.

Granulomatous interstitial nephritis in a renal allograft.

We describe a middle-aged woman in whom granulomatous interstitial nephritis (GIN) developed in a renal allograft. She had undergone bowel resection due to an uncertain diagnosis of active granulomatous bowel disease 30 years earlier. Thereafter, frequent hyperoxaluria as well as calcium oxalate stone and recurrent urinary tract infections had resulted in a progressive deterioration in kidney function over a period of 20 years.

Disappearance of association in diabetic patients on hemodialysis between anemia and mortality risk: the Japan dialysis outcomes and practice pattern study.

We previously demonstrated that anemia was not associated with mortality in hemodialysis patients with cardiovascular disease (CVD). Since diabetes mellitus (DM) accelerates CVD, the influence of DM on the relationship between anemia and mortality was examined using the data obtained from 1,385 DM patients and 2,583 non-DM hemodialysis patients recruited into the Dialysis Outcomes Practice Pattern Study in Japan (J-DOPPS). When all patients were stratified into four groups on their hematocrit levels, mortality rate was significantly and steadily lower in the subgroups with the higher levels of hematocrit by the Kaplan-Meier method (p = 0.

Turnover of focal adhesions and cancer cell migration.

Cells are usually surrounded by the extracellular matrix (ECM), and adhesion of the cells to the ECM is a key step in their migration through tissues. Integrins are important receptors for the ECM and form structures called focal adhesions (FAs). Formation and disassembly of FAs are regulated dynamically during cell migration.

Vitamin D receptor activators inhibit vascular smooth muscle cell mineralization induced by phosphate and TNF-α.

Background: Vascular calcification is a highly regulated process. Tumor necrosis factor-α (TNF-α) has been shown to accelerate the highly regulated osteogenic process in vascular smooth muscle cells (VSMCs). Vitamin D receptor activators (VDRAs) have been associated with beneficial cardiovascular outcomes in patients with chronic kidney disease.

Olmesartan medoxomil is associated with decreased plasma AGEs, pentosidine, and N-(epsilon)-carboxymethyl-lysine levels in hemodialysis patients.

Background: Advanced glycation end products (AGEs) are associated with comorbidity and death among patients on hemodialysis (HD). Angiotensin II type 1 receptor blockers (ARBs) can decrease the formation of AGEs in vitro. This study examines the ability of various ARBs to decrease plasma AGE levels in hypertensive patients on HD.

[Bone and calcium update; diagnosis and therapy of metabolic bone disease update. Advances in treatment of CKD-MBD].

Secondary hyperparathyroidism and vascular calcification are major clinical states in CKD-MBD (chronic kidney disease-mineral and bone disorder) . Recently fibroblast growth factor 23-klotho axis has been shown to be implicated in the pathogenesis of secondary hyperparathyroidism. Vascular calcification has been identified to be a highly regulated process.

Oxidized high-density lipoprotein as a risk factor for cardiovascular events in prevalent hemodialysis patients.

Background And Objectives: Here, we assessed the impact of oxidized high-density lipoprotein (oxHDL), dysfunctional HDL, on mortality and cardiovascular disease (CVD) events in prevalent HD patients and compared oxHDL to interleukin-6 (IL-6), a strong predictor of CVD events in HD patients.

Design, Setting, Participants, And Measurements: This prospective study examined a cohort of prevalent HD patients (n=412). Blood samples were obtained at baseline to measure lipids, high-sensitive C-reactive protein (hsCRP), IL-6, oxidized low-density lipoprotein, N-terminal pro B-type natriuretic peptide, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase, adiponectin, and oxHDL.

IL-17A stimulates granulocyte colony-stimulating factor production via ERK1/2 but not p38 or JNK in human renal proximal tubular epithelial cells.

We investigated the potential role of IL-17A in the induction of granulocyte colony-stimulating factor (G-CSF), a critical granulopoietic growth factor, in human renal proximal tubular epithelial cells. Human renal proximal tubular cells (HK-2, ATCC) were used to characterize the effects of IL-17A or IL-17F on G-CSF production, using ELISA, real-time RT-PCR, and immunoblotting. The cell surface expression of IL-17 receptors (IL-17Rs) was analyzed by flow cytometry.

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.

The blood compatibilities of blood purification membranes and other materials developed in Japan.

The biocompatibilities in blood purification therapy are defined as "a concept to stipulate safety of blood purification therapy by an index based on interaction in the body arising from blood purification therapy itself." The biocompatibilities are associated with not only materials to be used but also many factors such as sterilization method and eluted substance. It is often evaluated based on impacts on cellular pathways and on humoral pathways.

Olmesartan medoxomil treatment is associated with decreased plasma B-type natriuretic peptide levels in patients on hemodialysis.

Background: High levels of plasma B-type natriuretic peptide (BNP) are associated with cardiac heart failure and death among patients on hemodialysis (HD). A recent study has demonstrated that the angiotensin II type 1 receptor blocker lowers BNP concentrations. Here, we examined whether the ability of olmesartan medoxomil (OM; a novel angiotensin II type 1 receptor blocker) to decrease plasma BNP levels is concentration dependent in hypertensive patients on HD.