Use of darbepoetin alfa in the treatment of anaemia of chronic kidney disease: clinical and pharmacoeconomic considerations

The introduction of erythropoiesis-stimulating agents (ESAs) into everyday clinical practice has greatly improved the care of patients with chronic kidney disease. ESAs have reduced the need for blood transfusions, improved survival, decreased cardiovascular complications and enhanced patient quality of life. The longer acting ESA, darbepoetin alfa (Aranesp®), which can be administered less frequently than traditional ESAs, provides further benefits to both patients and healthcare professionals relative to the epoetins. Clinical studies have shown that darbepoetin alfa administered once every 2 weeks or once every month allows enhanced convenience and cost savings with no compromise in efficacy, while maintaining patients within target haemoglobin ranges

Burden of anemia in patients with osteoarthritis and rheumatoid arthritis in French secondary care

<p>Abstract</p> <p>Background</p> <p>Arthritic disorders can be the cause of hospitalizations, especially among individuals 60 years and older. The objective of this study is to investigate associations between health care resource utilization in arthritis patients with and without concomitant anemia in a secondary care setting in France.</p> <p>Methods</p> <p>This retrospective cohort study utilized data on secondary care activity in 2001 from the Programme de Médicalisation des Systèmes d'Information database. Two cohorts were defined using ICD-10 codes: patients with an arthritis diagnosis with a concomitant diagnosis of anemia; and arthritis patients without anemia. Health care resource utilization for both populations was analyzed separately in public and private hospitals. Study outcomes were compared between the cohorts using standard bivariate and multivariable methods.</p> <p>Results</p> <p>There were 300,865 hospitalizations for patients with arthritis only, and 2,744 for those with concomitant anemia. Over 70% of patients with concomitant anemia were in public hospitals, compared with 53.5% of arthritis-only patients. Arthritis patients without anemia were younger than those with concomitant anemia (mean age 66.7 vs 74.6, public hospitals; 67.1 vs 72.2, private hospitals). Patients with concomitant anemia/arthritis only had a mean length of stay of 11.91 (SD 14.07)/8.04 (SD 9.93) days in public hospitals, and 10.68 (SD 10.16)/9.83 (SD 7.76) days in private hospitals. After adjusting for confounders, the mean (95% CI) additional length of stay for arthritis patients with concomitant anemia, compared with those with arthritis only, was 1.56 (1.14-1.98) days in public and 0.69 (0.22-1.16) days in private hospitals. Costs per hospitalization were €;480 (227-734) greater for arthritis patients with anemia in public hospitals, and €;30 (-113-52) less in private hospitals, than for arthritis-only patients.</p> <p>Conclusions</p> <p>Arthritis patients with concomitant anemia have a longer length of stay, undergo more procedures, and have higher hospitalization costs than nonanemic arthritis patients in public hospitals in France. In private hospitals, concomitant anemia was associated with modest increases in length of stay and number of procedures; however, this did not translate into higher costs. Such evidence of anemia-related health care utilization and costs can be considered as a proxy for the clinical significance of anemia.</p

Low documentation of chronic kidney disease among high-risk patients in a managed care population: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Early detection of chronic kidney disease (CKD) is sub-optimal among the general population and among high risk patients. The prevalence and impact of major CKD risk factors, diabetes (DM) and hypertension (HTN), on CKD documentation among managed care populations have not been previously reported. We examined this issue in a Kaiser Permanente Georgia (KPG) CKD cohort.</p> <p>Methods</p> <p>KPG enrollees were included in the CKD cohort if they had eGFRs between 60 and 365 days apart that were <90 ml/min during 1999-2006. The current analysis is restricted to participants with eGFR 10-59 ml/min/1.73 m². CKD documentation was defined as a presenting diagnosis of CKD by a primary care physician or nephrologist using ICD-9 event codes. The association between CKD documentation and DM and HTN were assessed with multivariate logistic regression models.</p> <p>Results</p> <p>Of the 50,438 subjects within the overall KPG CKD cohort, 20% (N = 10,266) were eligible for inclusion in the current analysis. Overall, CKD diagnosis documentation was low; only 14.4% of subjects had an event-based CKD diagnosis at baseline. Gender and types 2 diabetes interacted on CKD documentation. The prevalence of CKD documentation increased with the presence of hypertension and/or type 2 diabetes, but type 2 diabetes had a lower effect on CKD documentation. In multivariate analysis, significant predictors of CKD documentation were eGFR, hypertension, type 2 diabetes, congestive heart failure, peripheral artery disease, statin use, age and gender. CKD documentation was lower among women than similarly affected men.</p> <p>Conclusion</p> <p>Among patients with an eGFR 10-59, documentation of CKD diagnosis by primary and subspecialty providers is low within a managed care patient cohort. Gender disparities in CKD documentation observed in the general population were also present among KPG CKD enrollees.</p

Transferrin changes in haemodialysed patients

Transferrin (Tf) is a glycoprotein responsible for iron transport in the human body. Physiologically in reaction with Concanavalin A, Tf occurs in four distinct variants Tf1, Tf2, Tf3 (apo-Tf) and Tf4. It was reported recently that Tf is changing, particularly during acute phase response, taking place among others in end-stage renal disease. In this study, we wanted to find the answer to three main questions: firstly, how Tf is changing in patients treated with maintenance haemodialysis (mHD), secondly, whether there are any Tf changes in the course of mHD treatment, and thirdly, what factors can affect Tf microheterogeneity in these patients. Studies were performed on 80 haemodialysed patients and 21 healthy volunteers. The Tf concentration was determined by the rocket immunoelectrophoresis, and its microheterogeneity was assessed by the ConA crossed immunoaffinity electrophoresis. During the annual observation of the distribution of the Tf variants, we have found both changes of the percentage contents of all Tf variants in the whole Tf concentration and a significant decrease in Tf2, Tf3 and Tf4 serum concentrations. Moreover, we found that decrease in the renal function, duration of mHD, and inflammation may contribute to these above-mentioned changes, which are probably the factors that should be taken into account when explaining the mechanisms of persistence of anaemia in haemodialysed patients

Mineral Composition is Altered by Osteoblast Expression of an Engineered Gs-Coupled Receptor

Activation of the Gs G protein–coupled receptor Rs1 in osteoblasts increases bone mineral density by 5- to 15-fold in mice and recapitulates histologic aspects of fibrous dysplasia of the bone. However, the effects of constitutive Gs signaling on bone tissue quality are not known. The goal of this study was to determine bone tissue quality in mice resulting from osteoblast-specific constitutive Gs activation, by the complementary techniques of FTIR spectroscopy and synchrotron radiation micro-computed tomography (SRμCT). Col1(2.3)-tTA/TetO-Rs1 double transgenic (DT) mice, which showed osteoblast-specific constitutive Gs signaling activity by the Rs1 receptor, were created. Femora and calvariae of DT and wild-type (WT) mice (6 and 15 weeks old) were analyzed by FTIR spectroscopy. WT and DT femora (3 and 9 weeks old) were imaged by SRμCT. Mineral-to-matrix ratio was 25% lower (P = 0.010), carbonate-to-phosphate ratio was 20% higher (P = 0.025), crystallinity was 4% lower (P = 0.004), and cross-link ratio was 11% lower (P = 0.025) in 6-week DT bone. Differences persisted in 15-week animals. Quantitative SRμCT analysis revealed substantial differences in mean values and heterogeneity of tissue mineral density (TMD). TMD values were 1,156 ± 100 and 711 ± 251 mg/cm3 (mean ± SD) in WT and DT femoral diaphyses, respectively, at 3 weeks. Similar differences were found in 9-week animals. These results demonstrate that continuous Gs activation in murine osteoblasts leads to deposition of immature bone tissue with reduced mineralization. Our findings suggest that bone tissue quality may be an important contributor to increased fracture risk in fibrous dysplasia patients

Epigenetic regulation of fetal bone development and placental transfer of nutrients: progress for osteoporosis

Osteoporosis is a common age-related disorder and causes acute and long-term disability and economic cost. Many factors influence the accumulation of bone minerals, including heredity, diet, physical activity, gender, endocrine functions, and risk factors such as alcohol, drug abuse, some pharmacological drugs or cigarette smoking. The pathology of bone development during intrauterine life is a factor for osteoporosis. Moreover, the placental transfer of nutrients plays an important role in the building of bones of fetuses. The importance of maternal calcium intake and vitamin D status are highlighted in this review. Various environmental factors including nutrition state or maternal stress may affect the epigenetic state of a number of genes during fetal development of bones. Histone modifications as histone hypomethylation, histone hypermethylation, hypoacetylation, etc. are involved in chromatin remodeling, known to contribute to the epigenetic landscape of chromosomes, and play roles in both fetal bone development and osteoporosis. This review will give an overview of epigenetic modulation of bone development and placental transfer of nutrients. In addition, the data from animal and human studies support the role of epigenetic modulation of calcium and vitamin D in the pathogenesis of osteoporosis. We review the evidence suggesting that various genes are involved in regulation of osteoclast formation and differentiation by osteoblasts and stem cells. Epigenetic changes in growth factors as well as cytokines play a rol in fetal bone development. On balance, the data suggest that there is a link between epigenetic changes in placental transfer of nutrients, including calcium and vitamin D, abnormal intrauterine bone development and pathogenesis of osteoporosis

Surface-Enhanced Nitrate Photolysis on Ice

Heterogeneous nitrates photolysis is the trigger for many chemical processes occurring in the polar boundary layer and is widely believed to occur in a quasi-liquid layer (QLL) at the surface of ice. The dipole forbidden character of the electronic transition relevant to boundary layer atmospheric chemistry and the small photolysis/photoproducts quantum yields in ice (and in water) may confer a significant enhancement and interfacial specificity to this important photochemical reaction at the surface of ice. Using amorphous solid water films at cryogenic temperatures as models for the disordered interstitial air/ice interface within the snowpack suppresses the diffusive uptake kinetics thereby prolonging the residence time of nitrate anions at the surface of ice. This approach allows their slow heterogeneous photolysis kinetics to be studied providing the first direct evidence that nitrates adsorbed onto the first molecular layer at the surface of ice are photolyzed more effectively than those dissolved within the bulk. Vibrational spectroscopy allows the ~3-fold enhancement in photolysis rates to be correlated with the nitrates’ distorted intramolecular geometry thereby hinting at the role played by the greater chemical heterogeneity in their solvation environment at the surface of ice than in the bulk. A simple 1D kinetic model suggests 1-that a 3(6)-fold enhancement in photolysis rate for nitrates adsorbed onto the ice surface could increase the photochemical NO[subscript 2] emissions from a 5(8) nm thick photochemically active interfacial layer by 30%(60)%, and 2-that 25%(40%) of the NO[subscript 2] photochemical emissions to the snowpack interstitial air are released from the top-most molecularly thin surface layer on ice. These findings may provide a new paradigm for heterogeneous (photo)chemistry at temperatures below those required for a QLL to form at the ice surface

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

End-stage kidney disease due to haemolytic uraemic syndrome - outcomes in 241 consecutive ANZDATA Registry cases

Extent: 11p.Background: The aim of this study was to investigate the characteristics and outcomes of patients receiving renal replacement therapy for end-stage kidney disease (ESKD) secondary to haemolytic uraemic syndrome (HUS). Methods: The study included all patients with ESKD who commenced renal replacement therapy in Australia and New Zealand between 15/5/1963 and 31/12/2010, using data from the ANZDATA Registry. HUS ESKD patients were compared with matched controls with an alternative primary renal disease using propensity scores based on age, gender and treatment era. Results: Of the 58422 patients included in the study, 241 (0.4%) had ESKD secondary to HUS. HUS ESKD was independently associated with younger age, female gender and European race. Compared with matched controls, HUS ESKD was not associated with mortality on renal replacement therapy (adjusted hazard ratio [HR] 1.14, 95% CI 0.87-1.50, p = 0.34) or dialysis (HR 1.34, 95% CI 0.93-1.93, p = 0.12), but did independently predict recovery of renal function (HR 54.01, 95% CI 1.45-11.1, p = 0.008). 130 (54%) HUS patients received 166 renal allografts. Overall renal allograft survival rates were significantly lower for patients with HUS ESKD at 1 year (73% vs 91%), 5 years (62% vs 85%) and 10 years (49% vs 73%). HUS ESKD was an independent predictor of renal allograft failure (HR 2.59, 95% CI 1.70-3.95, p < 0.001). Sixteen (12%) HUS patients experienced failure of 22 renal allografts due to recurrent HUS. HUS ESKD was not independently associated with the risk of death following renal transplantation (HR 0.92, 95% CI 0.35-2.44, p = 0.87). Conclusions: HUS is an uncommon cause of ESKD, which is associated with comparable patient survival on dialysis, an increased probability of renal function recovery, comparable patient survival post-renal transplant and a heightened risk of renal transplant graft failure compared with matched ESKD controls.Wen Tang, Janaki Mohandas, Stephen P McDonald, Carmel M Hawley, Sunil V Badve, Neil Boudville, Fiona G Brown, Philip A Clayton, Kathryn J Wiggins, Kym M Bannister, Scott B Campbell and David W Johnso