Risk factors for vitamin D deficiency in patients with chronic kidney disease.

OBJECTIVE: We conducted a cohort study to identify the risk factors for vitamin D deficiency in predialyzed patients with chronic kidney disease (CKD). METHODS: An observational study of 135 outpatients with stage 3-5 CKD was undertaken. Clinical and biochemical parameters were analyzed in terms of nutritional status, inflammation, and mineral metabolism in relation to serum levels of 25-hydroxyvitamin D [25(OH)D]. Levels of 25(OH)D lower than 15 ng/mL were considered to be deficient. RESULTS: The 25(OH)D-deficient group had a higher body mass index (24.1±4.2 kg/m(2) vs. 22.5±4.0 kg/m(2), p=0.0322), and had more diabetic patients (27.9% vs. 3.6%, p=0.0003). The multivariate analysis revealed that body mass index (odds ratio=2.758; 95% CI, 1.048-7.721; p=0.0398), the presence of diabetes (odds ratio=7.792; 95% CI, 1.808-55.439; p=0.0043), lower hemoglobin concentration (odds ratio=0.297; 95% CI, 0.099-8.732; p=0.821), higher serum levels of non-HDL cholesterol (odds ratio=3.570; 95% CI, 1.449-9.442; p=0.0053) and triglyceride (odds ratio=2.447; 95% CI, 0.779-1.776; p=0.0258) were the factors associated with low 25(OH)D levels. CONCLUSION: Vitamin D deficiency was common among the predialysis CKD patients, and the factors identified as being associated with vitamin D deficiency were diabetes and obesity.

Serum non-high-density lipoprotein cholesterol (non-HDL-C) levels and cardiovascular mortality in chronic hemodialysis patients.

BACKGROUND: Non-high-density lipoprotein cholesterol (non-HDL-C) has been proposed as a predictor of cardiovascular disease (CVD) in the general population. The aim of this study was to evaluate the utility of non-HDL-C in predicting CV mortality in chronic hemodialysis (HD) patients. METHODS: We calculated the serum non-HDL-C level of 259 HD patients by subtracting their HDL-C levels from their total cholesterol. Cox proportional hazards models were used to estimate the hazards ratio (HR) for CV mortality and the 95% confidence interval (CI). A receiver-operating characteristic (ROC) analysis was performed to estimate the relationship between sensitivity and specificity of a diagnostic parameter. RESULTS: There were 44 deaths (17.0%) during the follow-up period, 33 (12.7%) of which were due to CVD. A multivariate Cox analysis with adjustments for age, diabetes, dialysis vintage, systolic blood pressure, serum albumin, and lipid levels showed that non-HDL-C was an independent predictor of CV mortality (HR 1.015, 95% CI 1.004-1.025, p = 0.0083). An ROC analysis showed that the plots of the non-HDL-C levels yielded significant specificity and sensitivity for predicting the risk of CVD mortality in HD patients [area under the curve (AUC) 0.62416; p = 0.0366; cutoff value 111.0 mg/dl]. The Kaplan-Meier survival curves of HD patients showed significant differences in CV mortality according to their tertiles with respect to serum non-HDL-C levels (p = 0.0165). CONCLUSION: The results of this study suggest that serum non-HDL-C level is a significant CV mortality predictor of chronic HD patients.

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.

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.

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.