Relationship between responsiveness to erythropoiesis-stimulating agent and long-term outcomes in chronic hemodialysis patients: a single-center cohort study.

BACKGROUND: Responsiveness to erythropoietin-stimulating agent (ESA) may be associated with mortality risk in hemodialysis (HD) patients. The aim of the present study was to assess the relationship between responsiveness to ESA and long-term outcome in chronic HD patients. METHODS: Patients on HD therapy for more than 6 months were enrolled in this cohort study. The first year was used to assess the longitudinal dialysis status of patients; the subsequent years were used to assess the time-dependent risk of all-cause mortality. Hazard ratios were estimated using a Cox proportional model for the association between ESA dose and hemoglobin (Hb) level and mortality, adjusting for potential confounders. The ESA resistance index (ERI) was determined as the weekly weight-adjusted dose of ESA divided by Hb concentration. Patients were divided into three groups by tertiles of ERI. RESULTS: Of the 320 subjects enrolled, 105 died during the follow-up period of 70.4 ± 29.0 months. When subjects were stratified by epoetin dose and Hb level into four groups, those who had low Hb despite a high dose of epoetin were associated with the highest risk of mortality among the four groups (adjusted hazard ratio 1.86; 95 % confidence interval 1.25-2.75). These highest risk subjects had older age, lower body mass index, and lower serum levels of albumin, triglyceride, and transferring saturation. The impact of serum albumin and serum ferritin on mortality risk in an adjusted Cox proportional hazards model was in accordance with low Hb and higher ESA. There was no significant difference between the mortality risk and tertile of ERI. CONCLUSIONS: High ESA dose and low Hb level were associated with an increased risk of all-cause mortality. However, the responsiveness to ESA estimated by ERI was not related to mortality risk. These findings suggest that the responsiveness to ESA should be evaluated by different methods in HD patients.

Additional reduction in serum phosphorus levels by pulverized lanthanum carbonate chewable in hemodialysis patients.

Lanthanum carbonate (LC) is one of the relatively new phosphate binders. The general LC dosage form is a chewable pharmaceutical preparation. This investigation was targeted to subjects who do not chew LC chewable preparations adequately, for the purpose of studying the clinical efficacy of changing to pulverized prescriptions, such as changes in serum phosphorus levels (P levels). The study took place at Minamisenju Hospital in October 2011, with 41 subjects on maintenance hemodialysis. We pulverized all of the LC chewable medicines of the LC insufficient mastication group (non-chewing: NC group, n = 18) using a crusher, and changed them to pulverized prescriptions. The testing period was set at 10 weeks. In the NC group, there was a significant lowering of P levels from 5.86 ± 1.31 mg/dL before pulverization of the LC chewable preparation (week 0) to 5.38 ± 1.26 mg/dL after 2 weeks of administration of the pulverized medication (P = 0.0310), 5.20 ± 1.25 mg/dL after 4 weeks (P = 0.0077), and 5.12 ± 1.34 mg/dL after 6 weeks (P = 0.0167). P levels in other patients than NC group showed no significant change. In this study, the P levels in the NC group was lowered significantly by changing the LC chewable to the pulverized prescription, and the residual LC images on the abdominal X-rays disappeared to the point where they could barely be confirmed.

Serum osteocalcin levels are useful as a predictor of cardiovascular events in maintenance hemodialysis patients.

BACKGROUNDS: Osteocalcin (OC) is a known bone metabolic marker and a regulator of glucose and fat metabolisms. Although bone and energy metabolisms are known risk factors for cardiovascular disease (CVD) in hemodialysis (HD) patients, few studies have examined the correlation between OC and CVD. The purpose of this study was to investigate the impact of serum OC levels on the emergence of new CVD events in HD patients. METHODS: We designed a longitudinal, observational cohort study in which the study patients were divided into low- and high-serum OC groups based on a median serum OC level of 71.5 ng/ml. RESULTS: Cardiovascular disease events were observed in 29 of 126 patients (23.0 %). The number of cumulative CVD events in the low-serum OC group was significantly higher than that in the high-serum OC group, as evaluated by the Kaplan-Meier method (p = 0.0021, log-rank test). Multivariate Cox proportional hazards analysis demonstrated that a low level of serum OC is a significant predictor of a higher incidence of CVD events [hazard ratio, 2.925; 95 % confidence interval, 1.048-9.066; p = 0.0401] after adjustment. CONCLUSION: Serum OC level is a significant, independent prognostic factor for CVD events in maintenance HD patients. OC may be useful in predicting new CVD events in HD patients.

Left atrial volume is an independent predictor of all-cause mortality in chronic hemodialysis patients.

OBJECTIVE: An enlarged left atrium (LA) has recently been identified as a risk factor for adverse cardiovascular outcomes in various pathologic conditions. However, few studies have evaluated its prognostic value in hemodialysis (HD) patients. METHODS: We conducted an observational study to investigate whether an enlarged LA predicted all-cause mortality in 174 HD patients. Patients were stratified into two groups based on the LA volume index (LAVI) value of 32 mL/m2. RESULTS: An increased left atrial volume index (LAVI >32 mL/m(2)) was present in 28 (16.1%) of the HD patients. During the follow-up period (50.1 ± 22.4 months), 77 patients (44.3%) died. A Kaplan-Meier analysis revealed that the 7-year survival rate was significantly lower in the group whose LAVI was >32 mL/m(2) than in the group whose LAVI was ≤ 32 mL/m(2) (p=0.0033). Multivariate analyses adjusted for echocardiographic parameters and clinical and laboratory data showed that increased LAVI was an independent predictor of all-cause mortality (hazard ratio 1.030, 95% confidence interval 1.004-1.056, p=0.0260). Moreover, increased LAVI had a higher predictive value for all-cause mortality (area under the receiver operating characteristic curve=0.612, p=0.0059) among the measured echocardiographic parameters. CONCLUSION: The results of the present study suggested that measurement of LAVI may be helpful in the risk stratification of HD patients and in providing therapeutic direction for their management.

Correlation of new bone metabolic markers with conventional biomarkers in hemodialysis patients.

BACKGROUND: New bone metabolic markers have become available clinically for evaluating chronic kidney disease mineral and bone disorders (CKD-MBD). The aim of this study was to correlate these new bone metabolic markers with conventional markers in regular hemodialysis (HD) patients. METHODS: One hundred forty three HD patients underwent cross-sectional assessment. Two bone formation markers, bone-specific alkaline phosphatase (BAP) and osteocalcin (OC), and one bone resorption marker, amino-terminal telopeptides of type 1 collagen (NTx), were selected for study. RESULTS: Both circulating OC and NTx levels showed positive correlations with serum intact parathyroid hormone (iPTH) levels. The levels of NTx and OC showed a strongly positive correlation, although they are known to be markers of different aspects of bone metabolism: bone formation and resorption. Patients with high iPTH (≥300pg/mL) had significantly higher levels of all the three bone markers compared with patients with low or normal iPTH . CONCLUSION: Serum OC and NTx levels may be useful markers of serum iPTH levels for evaluating bone turnover in HD patients and may eventually prove useful in the management of patients with CKD-MBD.

Clinical outcomes in patients with chronic kidney disease: a 5-year retrospective cohort study at a University Hospital in Japan.

BACKGROUND: Latent chronic kidney disease (CKD) population appears to be a serious health problem in Japan. The purposes of the present study were to determine risk factors for CKD progression and to evaluate the rate of decline in estimated glomerular filtration rate (eGFR). METHODS: A retrospective cohort study of adult patients with CKD was conducted at a University Hospital in Japan. The primary outcome was rate of change in eGFR over time. Age-based eGFR was calculated by the Modification of Diet in Renal Disease study equation for Japan. Blood and urine specimens were collected at study entry along with information regarding blood pressure (BP), body mass index and medications. Patients were monitored for up to 5 years. RESULTS: A total of 1115 patients were enrolled with mean (SD) age of 63.1 (16.5) years; 43.1% were women, and 16.4% had diabetes. At study entry, body mass index was 23.3 (3.9) kg/m(2), and mean BP was 125.4 (16.0) mmHg. Systolic BP, creatinine, uric acid and urinary protein levels differed significantly among patients grouped by CKD stages, and the values tended to increase in the higher disease stages. Time-to-event analysis showed that 3.45% of patients experienced a 50% eGFR decline. The slope of the eGFR decline was -1.01 (mL/min per 1.73 m(2)) per year, as assessed by repeated-measures analysis (-1.18 in men and -0.78 in women). In addition, the slope of the decline tended to be smaller in the higher CKD stages (stage 5, -0.31%; stage 4, -1.32%; stage 3, -0.75%; stage 2, -1.10%; stage 1, -2.33%). Serum creatinine and diabetes were identified as predictors of CKD progression by time-to-event analysis, but not by repeated-measures analysis. Conversely, urinary occult blood, blood glucose, and treatment with angiotensin-converting enzyme inhibitors, and anti-platelet agents were identified by repeated-measures analysis but not by time-to-event analysis. CONCLUSIONS: The slope of the eGFR decline was influenced by CKD stages, underlying diseases and medications taken by patients. Long-term follow-up of patients will provide critical insights into factors affecting progression of CKD.

Cardiovascular autonomic neuropathy studied by a laser-Doppler blood flowmeter in hemodialysis patients.

OBJECTIVE: Orthostatic hypotension during a hemodialysis (HD) session affects not only the modality but daily quality of life for HD patients because many of them have combined dysfunction of both sympathetic and parasympathetic nervous systems. Although various non-invasive methods have been applied for the evaluation of autonomic function, no monitor has been devised for measuring the dysfunction during blood purification therapy. PATIENTS AND METHODS: We evaluated the usefulness of laser-Doppler blood flowmeter (LDF) for measuring autonomic function of stable 34 regular HD patients and 24 healthy controls. The LDF device was applied for autonomic test by measuring periflux blood flow decreasing velocity (PDV) accompanied with Valsalva maneuver. We also evaluated the correlation between PDV and conventional tests for atherosclerosis. RESULTS: The average PDV (3.79±1.77) in HD population level was significantly lower than that of healthy controls (8.72±6.00). We also found a significant correlation between PDV and conventional methods such as heart rate variability and ankle-brachial blood pressure index. CONCLUSION: Measurement of PDV by LDF is as useful as a conventional method for evaluating autonomic function in HD patients. The convenience of the device offers the benefit of daily and frequent measurement of autonomic dysfunction.

A case of AL amyloidosis with renal rupture.

We report a 59-year-old woman with AL amyloidosis who presented with massive bleeding from the right kidney, in whom emergency surgery proved to be life saving. The patient had been diagnosed as having AL amyloidosis 16 years previously. After 5 years, hemodialysis had been initiated. In 2007, a large right-sided perinephric, intracapsular hematoma was detected. Right nephrectomy was performed and the patient recovered with no sequelae. Histopathological examination revealed a greater degree of amyloid deposition in the resected kidney than that at the time of diagnosis. Amyloid angiopathy may promote bleeding.

Suppression of renal fibrosis by galectin-1 in high glucose-treated renal epithelial cells.

Diabetic nephropathy is the most common cause of chronic kidney disease. We investigated the ability of intracellular galectin-1 (Gal-1), a prototype of endogenous lectin, to prevent renal fibrosis by regulating cell signaling under a high glucose (HG) condition. We demonstrated that overexpression of Gal-1 reduces type I collagen (COL1) expression and transcription in human renal epithelial cells under HG conditions and transforming growth factor-ß1 (TGF-ß1) stimulation. Matrix metalloproteinase 1 (MMP1) is stimulated by Gal-1. HG conditions and TGF-ß1 treatment augment expression and nuclear translocation of Gal-1. In contrast, targeted inhibition of Gal-1 expression reduces COL1 expression and increases MMP1 expression. The Smad3 signaling pathway is inhibited, whereas two mitogen-activated protein kinase (MAPK) pathways, p38 and extracellular signal-regulated kinase (ERK), are activated by Gal-1, indicating that Gal-1 regulates these signaling pathways in COL1 production. Using specific inhibitors of Smad3, ERK, and p38 MAPK, we showed that ERK MAPK activated by Gal-1 plays an inhibitory role in COL1 transcription and that activation of the p38 MAPK pathway by Gal-1 plays a negative role in MMP1 production. Taken together, two MAPK pathways are stimulated by increasing levels of Gal-1 in the HG condition, leading to suppression of COL1 expression and increase of MMP1 expression.