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ABSTRACT: 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.
International Urology and Nephrology 03/2012; · 1.47 Impact Factor
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ABSTRACT: 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.
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/m<sup>2</sup>.
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.
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.
Internal Medicine 01/2012; 51(12):1479-85. · 0.94 Impact Factor
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ABSTRACT: 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).
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.
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.
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.
Clinical and Experimental Nephrology 07/2011; 15(6):831-40. · 1.37 Impact Factor
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ABSTRACT: 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.
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.
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 .
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 and investigative medicine. Medecine clinique et experimentale 01/2011; 34(5):E267. · 1.15 Impact Factor
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ABSTRACT: 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-β1 (TGF-β1) stimulation. Matrix metalloproteinase 1 (MMP1) is stimulated by Gal-1. HG conditions and TGF-β1 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.
Experimental Cell Research 11/2010; 316(19):3282-91. · 3.58 Impact Factor
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ABSTRACT: 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.
Internal Medicine 01/2010; 49(19):2129-32. · 0.94 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Internal Medicine 01/2010; 49(24):2669-75. · 0.94 Impact Factor
