Evaluation of bone is of great importance in chronic kidney disease patients, as these patients are at an increased risk for fractures. We treated a hemodialysis patient suffering from ...hyperparathyroid bone disease with cinacalcet hydrochloride and concurrent administration of maxacalcitol and alfacalcidol for a year. Hyperparathyroid bone disease is characterized by cortical thinning, increased cortical porosity, reduced trabecular bone volume, and increased hypomineralized matrix volume, and there is little information to date about the effects of treatment with cinacalcet hydrochloride on the bone fragility in patients with hyperparathyroid bone disease. In the present study, histological and backscattered electron microscopic evaluation of this combination treatment revealed an excellent improvement of both bone volume and bone morphology. This treatment improved cortical thinning, cortical porosity, and trabecular thinning. Furthermore, the treatment also reduced hypomineralized matrix volume, indicative of improved mineralization by osteocytes. We speculate that the intermittent maxacalcitol administration may have effectively stimulated the vitamin D receptors expressed on osteocytes and osteoblasts, resulting in increased mineralization. Our approach for evaluating the bone in patients with chronic kidney disease by backscattered electron microscopy is novel.
Summary
Serum sclerostin levels could be closely associated with serum phosphate and fibroblast growth factor-23 levels in hemodialysis patients with low intact parathyroid hormone (PTH) levels. ...Further study is required to indicate whether these close associations are present in patients with spontaneously low PTH levels without any vitamin D treatment.
Introduction
Intact parathyroid hormone (iPTH) is involved in the interaction between sclerostin and phosphate/fibroblast growth factor-23 (FGF23) in animal models. However, their relationship in patients on hemodialysis (HD) is unclear.
Methods
Data of 102 HD patients were collected regarding clinical and laboratory parameters and mineral bone disorder medications. The patients were divided into subgroups according to the iPTH level (A, <70 pg/mL; B, 70–150 pg/mL; C, 150–300 pg/mL; and D, ≥300 pg/mL).
Results
The sclerostin level was significantly and positively correlated with phosphate and log of FGF23 levels in subgroups A, B, and combined A and B. Multiple linear regression analysis in the combined A and B subgroup revealed that male sex (
t
= 3.24,
P
= 0.01; 95 % confidence interval CI 11.78 to 50.43) and phosphate level (
t
= 2.13,
P
= 0.04; 95 % CI, 1.08 to 36.91) were independent factors for serum sclerostin level. The log of serum FGF23 level (
t
= 1.90,
P
= 0.06, 95 % CI −1.85 to 63.50) appeared to be an important factor for serum sclerostin level. The frequency of patients using vitamin D treatment was not significantly different among subgroups A (93.1 %), B (88.0 %), C (85.2 %), and D (90.5 %).
Conclusion
Serum sclerostin levels were associated with serum phosphate and FGF23 levels in patients with low iPTH levels. Further study is required to indicate whether these close associations are present in patients with spontaneously low iPTH levels without vitamin D treatment.
The emergence of kidney disease as an important comorbidity among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) has emphasized the ...critical importance of early identification of patients at risk for kidney disease. Use of urine as a diagnostic medium may allow the noninvasive detection of incipient nephropathy in these patients.
Here, we conducted cross-sectional and 1-year prospective studies of 424 HIV-infected patients on HAART without proteinuria or significant impairment of glomerular function. N-acetyl-β-D-glucosaminidase, γ-glutamyl transpeptidase, β(2)-microglobulin and α(1)-microglobulin were measured as indices of tubular damage, which was diagnosed when urinary concentrations of at least three tubular biomarkers exceeded the reference range. Risk factors associated with tubular damage were examined using multivariate logistic regression analysis.
Tubular damage was identified in 107 patients (25%), who were characterized by advanced age odds ratio (OR), 1.04; 95% confidence interval (CI), 1.01-1.07, high C-reactive protein (OR, 1.96; 95% CI, 1.26-3.14) and coexisting diabetes mellitus (OR, 3.97; 95% CI, 1.44-12.2). The use of tenofovir, the most likely tubulotoxic agent, was not statistically involved in this subclinical tubular damage. The 1-year follow-up study showed that a decrease in estimated glomerular filtration rate (eGFR) and incidence of proteinuria during the period were significantly higher in patients with than without tubular damage.
A quarter of HIV-infected patients receiving HAART had subclinical tubular damage, which was associated with a near-term decline in eGFR and higher incidence of proteinuria. Periodic monitoring of urinary biomarkers might facilitate the early identification of HAART patients predisposed to significant kidney disease.
Generally, the maximal expiratory flow-volume (MEFV) curve must be measured for the diagnosis and staging of chronic obstructive pulmonary disease (COPD). As this test is effort dependent, ...international guidelines recommend that three acceptable trials are required for each test. However, no study has examined the magnitude and factors for the variability in parameters among three acceptable trials.
We evaluated the intra-individual variations in several parameters among three acceptable MEFV curves obtained at one-time point in patients with COPD (n = 28, stage 1; n = 36, stage 2; n = 21, stages 3-4). Next, the factors for such variations were examined using forced expiratory volume in 1 second (FEV
) and forced vital capacity (FVC).
The averages of coefficient of variation (CV) for FEV
and FVC were 2.0% (range: 1.0-3.0%) and 1.6% (0.9-2.2%), respectively. Both parameters were significantly better than peak expiratory flow rate, forced expiratory flow at 50% of expired FVC, and forced expiratory flow at 75% of expired FVC (CVs: 5.0-6.9%). A higher spirometric stage was significantly associated with higher CVs for FVC and FEV
and older age was significantly correlated with a higher variation in FEV
alone. Furthermore, a significantly inverse association was observed between emphysema severity, and the CVs for FEV
, but not that for FVC, regardless of spirometric stage.
Both FVC and FEV
are highly reproducible; nevertheless, older age, lower FEV
at baseline, and non-emphysema phenotype are factors for a higher variability in FEV
in patients with COPD.
Background. Chronic kidney disease (CKD) seems to be common in long-term survivors of haematopoietic cell transplantation (HCT). However, the range of its frequency is very wide, likely due to ...variability in the definitions of CKD and the periods of follow-up. Methods. We conducted a cross-sectional and retrospective study in 158 adults who received myeloablative allogeneic HCT for lymphohaematologic malignancies at least 3 years ago and are alive today. The mean survival time was 6.15 ± 4.88 years (range: 3–16 years). CKD was defined as a sustained decrease in glomerular filtration rate (GFR) or persistent proteinuria for a period more than 3 months. GFR was calculated based on serum creatinine (Cr) using the Modification of Diet in Renal Disease formula. Serum Cr and proteinuria were measured at least on three occasions separated by one or more months before the investigation. CKD was classified according to the National Kidney Foundation CKD staging. Proteinuria was defined as positive dipstick test ≥1+. The factors associated with the presence of CKD with a decrease of GFR (CKD ≥ stage 3) were examined using multivariate logistic regression analysis, adjusted for demographic and clinical characteristics. Results. The prevalence of proteinuria was found in 36 out of 158 patients (22.8%). The prevalence of each CKD stage was as follows: Stage 0 (no CKD), 98 patients (62.0%); Stage 1, 18 patients (11.4%); Stage 2, 15 patients (9.5%); Stage 3, 8 patients (5.1%); Stage 4, 10 patients (6.3%) and Stage 5, 9 patients (5.7%). Initiation of chronic dialysis treatment or transplant was performed in seven CKD stage-5 patients (4.4%) at a mean of 10.9 ± 3.72 years after HCT. Multivariate analysis identified acute kidney injury with HCT odds ratio (OR), 9.920; 95% confidence interval (CI), 2.084–39.68; P = 0.0051, hypertension after HCT (OR, 4.031; 95% CI, 1.044–13.06; P = 0.0346) and survival time after HCT (OR, 4.275; 95% CI, 2.823–23.04; P = 0.0481) as significant factors associated with the presence of CKD ≥ stage 3. Conclusions. A remarkably high percentage of long-term survivors had evidence of proteinuria and all stages of CKD. CKD in transplant recipients may result from incomplete recovery from acute renal insults, hypertension and increasing longevity. The CKD cohort should be at a great risk for end-stage renal disease and cardiovascular morbidity and mortality. The burden of CKD should be recognized as a significant public health problem.
The ductile fracture behavior under uniaxial tension of melt-crystallized isotactic polypropylene specimens at room temperature was investigated from a statistical point of view. Each tensile test ...was performed more than one hundred times and statistical data for the breaking point were obtained under each tensile condition. The probability distribution curves of the fracture time and strength approximately followed Gaussian statistics at lower tensile speeds, but changed to a Weibull function at higher-speed tests. Additionally, with increasing tensile speed the mean and standard deviation of the fracture time decreased linearly. The toughness, which is the total area under the stress-strain curves, was found to be independent of the tensile conditions, indicating that fracture toughness is a criterion for fracture under tension.
Toll-like receptors (TLRs) play a pivotal role in pathogen recognition and subsequent cytokine synthesis by immune cells. Uremic patients have a high infectious morbidity, but it remains unclear if ...this arises from the defective innate immune responses related to TLRs. We studied TLR4 expression in monocytes and their intracellular cytokine synthesis in response to lipopolysaccharide (LPS) stimulation in 35 predialysis patients with chronic kidney disease (CKD) with or without predisposition to bacterial infections and 16 age-matched controls. Expression of TLR4 in unstimulated peripheral monocytes was determined by staining with anti-TLR4 antibody and analysis with flow cytometry. Monocytes were then stimulated by LPS, labeled with anti-CD14 antibody, and subjected to intracellular cytokine staining and flow cytometry. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 synthesis was examined in CD14+ monocytes. TLR4 expression was constitutively diminished in CKD patients with reduced expression being more severe in those CKD patients who were predisposed to infections. Monocytes from these infection prone CKD patients exhibited significantly reduced synthesis of TNF-α, IL-1β, IL-6, and IL-8 in response to LPS challenge compared with those from control subjects. The intensity of synthesis of each cytokine significantly correlated with TLR4 expression levels in monocytes (P<0.01). The capacity of monocytes to synthesize proinflammatory cytokines was significantly reduced in infection prone CKD patients, and this may possibly be due to the reduced monocyte expression of TLR4. Abnormal TLR4 expression by monocytes may play a role in the susceptibility of such patients to bacterial infections.
Background. Osteoprotegerin (OPG) is a glycoprotein that inhibits osteoclast differentiation and activity. OPG-deficient mice develop severe osteoporosis and medial arterial calcification. The ...expression of OPG is detected in early atherosclerotic lesions in non-uraemic patients. We examined whether serum OPG is associated with aortic calcification in haemodialysis patients. Methods. Serum OPG was measured in 102 patients who were undergoing haemodialysis. The aortic calcification index (ACI) was assessed by computed tomography scans. Results. Serum OPG level, measured by enzyme-linked immunosorbent assay, was significantly greater in patients with higher ACI than in those with lower ACI. There was a direct relationship between ACI and serum OPG levels and a positive association between OPG and ACI (r = 0.483, P<0.0001). Multiple regression analyses indicated that serum OPG levels were independently associated with the severity of aortic calcification (P<0.0001). Conclusions. These findings show that serum OPG levels are associated with the extent of vascular calcification, suggesting that OPG may be involved in the development of vascular calcification in haemodialysis patients.
Performance of multi-pixel photon counters for the T2K near detectors Yokoyama, M.; Minamino, A.; Gomi, S. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
10/2010, Letnik:
622, Številka:
3
Journal Article
Recenzirano
Odprti dostop
We have developed a Multi-Pixel Photon Counter (MPPC) for the neutrino detectors of T2K experiment. About 64,000 MPPCs have been produced and tested in about a year. In order to characterize a large ...number of MPPCs, we have developed a system that simultaneously measures 64 MPPCs with various bias voltage and temperature. The performance of MPPCs are found to satisfy the requirement of T2K experiment. In this paper, we present the performance of 17,686 MPPCs measured at Kyoto University.
Background. Epidemiological studies have raised awareness of the problem of undiagnosed kidney disease and suggest that early identification and treatment will reduce the global burden of patients ...requiring dialysis. However, there are insufficient data on how to identify subjects who are at risk for developing overt kidney disease in a human immunodeficiency virus (HIV) population.
Methods. A 2-year prospective cohort study was conducted to determine the predictors of overt kidney disease. The cohort was comprised of a total of 507 HIV-infected participants with no evidence of kidney disease at baseline. Of which 429 participants completed the study. New-onset kidney disease was defined as the development of either microalbuminuria or renal dysfunction. Microalbuminuria was defined as urinary albumin-to-creatinine ratio (ACR) ≥30 mg/g. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Baseline ACR and eGFR were classified into three and two groups for analysis: 0-9, 10-19 and 20-29 mg/g and 60-89 and ≥90 mL/min/1.73 m2, respectively. Cox proportional hazards regression analysis was used to determine the baseline factors related to incident kidney disease.
Results. The incidence of microalbuminuria, renal dysfunction and both illness were 8.4, 4.7 and 0.93% during the 2-year follow-up period, respectively. Baseline predictors of the development of microalbuminuria included the following (hazard ratio with 95% confidence interval): (i) age, 1.03 (1.00-1.07); (ii) diabetes mellitus (DM), 4.41 (1.04-16.1); (iii) hepatitis C virus (HCV) coinfection, 7.91 (1.56-33.2); (iv) ACR 10-19 mg/g, 11.5 (3.51-52.6) and (v) ACR 20-29 mg/g, 49.0 (13.9-236). Baseline predictors of the development of renal dysfunction included the following: (i) age, 1.03 (1.00-1.12); (ii) baseline eGFR 60-89 mL/min/1.73 m2, 7.86 (2.11-51.5); (iii) ACR 10-19 mg/g, 3.88 (1.28-12.6); (iv) ACR 20-29 mg/g, 6.64 (1.65-26.3) and (v) exposure to tenofovir-boosted protease inhibitors, 7.17 (2.57-23.4). The risks increased greatly with increasing number of concurrent predictors.
Conclusions. Middle to high levels within the normal range of albuminuria is a significant risk factor for near-term development of overt kidney disease. In particular, HIV-infected patients with multiple risk factors including age, DM, HCV, low-grade albuminuria, a mild decrease in eGFR and use of tenofovir-boosted protease inhibitors should be closely monitored.
PDF
