Перспективи розвитку світової енергетики й забезпечення енергетичної безпеки України

Проблеми забезпечення енергетичної безпеки (ЕнБ) безпеки були та залишаються головними складовими забезпечення національної безпеки та загального сталого розвитку

Erythropoietin, Fibroblast Growth Factor 23, and Death After Kidney Transplantation

Elevated levels of erythropoietin (EPO) are associated with an increased risk of death in renal transplant recipients (RTRs), but the underlying mechanisms remain unclear. Emerging data suggest that EPO stimulates production of the phosphaturic hormone fibroblast growth factor 23 (FGF23), another strong risk factor for death in RTRs. We hypothesized that the hitherto unexplained association between EPO levels and adverse outcomes may be attributable to increased levels of FGF23. We included 579 RTRs (age 51 ± 12 years, 55% males) from the TransplantLines Insulin Resistance and Inflammation Cohort study (NCT03272854). During a follow-up of 7.0 years, 121 RTRs died, of which 62 were due to cardiovascular cause. In multivariable Cox regression analysis, EPO was independently associated with all-cause (HR, 1.66; 95% CI 1.16-2.36; P = 0.005) and cardiovascular death (HR, 1.87; 95% CI 1.14-3.06; P = 0.01). However, the associations were abrogated following adjustment for FGF23 (HR, 1.28; 95% CI 0.87-1.88; P = 0.20, and HR, 1.45; 95% CI 0.84-2.48; P = 0.18, respectively). In subsequent mediation analysis, FGF23 mediated 72% and 50% of the association between EPO and all-cause and cardiovascular death, respectively. Our results underline the strong relationship between EPO and FGF23 physiology, and provide a potential mechanism underlying the relationship between increased EPO levels and adverse outcomes in RTRs

Association of Hepcidin-25 with survival after kidney transplantation

Background Hepcidin is considered the master regulator of iron homoeostasis. Novel hepcidin antagonists have recently been introduced as potential treatment for iron-restricted anaemia. Meanwhile, serum hepcidin has been shown to be positively associated with cardiovascular disease and inversely with acute kidney injury. These properties may lead to contrasting effects, especially in renal transplant recipients (RTR), which are prone to cardiovascular diseases and graft failure. To date, the role of serum hepcidin in RTR is unknown. We, therefore, prospectively determined the association of serum hepcidin with risk of graft failure, cardiovascular mortality and all-cause mortality in RTR. Materials and methods Serum hepcidin was assessed in an extensively phenotyped RTR cohort by dual-monoclonal sandwich ELISA specific immunoassay. Statistical analyses were performed using univariate linear regression followed by stepwise backward linear regression. Cox proportional hazard regression models were performed to determine prospective associations. Results We included 561 RTR (age 51 +/- 12 years). Mean haemoglobin (Hb) was 8.6 +/- 1.0 mM. Median [IQR] serum hepcidin was 7.2 [3.2-13.4] ng/mL. Mean estimated glomerular filtration rate was 47 +/- 16 mL/min/ 1.73 m(2). In univariate Cox regression analyses, serum hepcidin was not associated with risk of graft failure, cardiovascular mortality or all-cause mortality. Notably, after adjustment for high sensitivity C-reactive protein and ferritin, serum hepcidin became negatively associated with all-cause mortality (hazard ratio 0.89; 95% confidence interval 0.80-0.99, P = 0.3). Conclusions In this study, we did not find an association between serum hepcidin and outcomes, that is graft failure, cardiovascular mortality or all-cause mortality. Based on our results, it is questionable whether serum hepcidin may be used to predict a beneficial effect of hepcidin antagonists

Laboratory measurements of electrical conductivities of hydrous and dry Mt. Vesuvius melts under pressure

International audienceQuantitative interpretation of MT anomalies in volcanic regions requires laboratory measurements of electrical conductivities of natural magma compositions. The electrical conductivities of three lava compositions from Mt. Vesuvius (Italy) have been measured using an impedance spectrometer. Experiments were conducted on both glasses and melts between 400 and 1300°C, and both at ambient pressure in air and at high pressures (up to 400 MPa). Both dry and hydrous (up to 5.6 wt% H2O) melt compositions were investigated. A change of the conduction mechanism corresponding to the glass transition was systematically observed. The conductivity data were fitted by sample-specific Arrhenius laws on either side of Tg. The electrical conductivity increases with temperature and is higher in the order tephrite, phonotephrite to phonolite. For the three compositions investigated, increasing pressure decreases the conductivity, although the effect of pressure is relatively small. The three compositions investigated have similar activation volumes (ΔV=16-24 cm3/mol). Increasing the water content of the melt increases the conductivity. Comparison of activation energies (Ea) from conductivity and sodium diffusion, and use of the Nernst-Einstein relation allow sodium to be identified as the main charge carrier in our melts and presumably also in the corresponding glasses. Our data and those of previous studies highlight the correlation between the Arrhenius parameters Ea and σ0. A semi-empirical method allowing the determination of the electrical conductivity of natural magmatic liquids is proposed, in which the activation energy is modelled on the basis of the Anderson-Stuart model, σ0 being obtained from the compensation law and ΔV fitted from our experimental data. The model enables the electrical conductivity to be calculated for the entire range of melt compositions at Mt. Vesuvius and also predicts satisfactorily the electrical response of other melt compositions. Electrical conductivity data for Mt. Vesuvius melts and magmas are slightly lower than the electrical anomaly revealed by MT studies

Relation between Red Cell Distribution Width and Fibroblast Growth Factor 23 Cleaving in Patients with Chronic Kidney Disease and Heart Failure

In chronic kidney disease (CKD), both anemia and deregulated phosphate metabolism are common and predictive of adverse outcome. Previous studies suggest that iron status influences phosphate metabolism by modulating proteolytic cleavage of FGF23 into C-terminal fragments. Red cell distribution width (RDW) was recently identified as a strong prognostic determinant for cardiovascular morbidity and mortality, independently of iron status. We assessed whether RDW is associated with FGF23 cleaving in CKD patients with heart failure.The associations between RDW and either intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23, reflecting iFGF23 and C-terminal fragments together) and the iFGF23/cFGF23 ratio were analyzed in 52 patients with CKD (eGFR 34,9 ± 13.9 ml/min/1.73m2) and chronic heart failure (CHF). Associations between RDW and FGF23 forms were studied by linear regression analysis adjusted for parameters of renal function, iron metabolism, phosphate metabolism and inflammation.Median cFGF23 levels were 197.5 [110-408.5] RU/ml, median iFGF23 levels were 107.3 [65.1-162.2] pg/ml and median FGF23 ratio was 0.80 [0.37-0.86]. Mean RDW was 14.1 ± 1.2%. cFGF23 and RDW were associated (β = 1.63 x 10(-3), P < 0.001), whereas iFGF23 and RDW were not (β = -1.38 x 10(-3), P = 0.336). The iFGF23/cFGF23 ratio was inversely associated with RDW. The difference between cFGF23 and iFGF23 (cFGF23- iFGF23) was positively associated with RDW (β = 1.74 x 10(-3), P < 0.001). The association between cFGF23 and RDW persisted upon multivariable linear regression analysis, adjusted for parameters of renal function, phosphate metabolism, iron metabolism and inflammation (β = 0.97 x 10(-3), P = 0.047).RDW is associated with cFGF23 but not with iFGF23 levels in patients with CKD and CHF. This suggests a connection between RDW and FGF23 catabolism, independent of iron status and inflammation. Future studies are needed to unravel underlying mechanisms and whether these pertain to the link between RDW and outcome

Interplay of erythropoietin, fibroblast growth factor 23, and erythroferrone in patients with hereditary hemolytic anemia

Recently, erythropoietin (EPO) was identified as regulator of fibroblast growth factor 23 (FGF23). Proteolytic cleavage of biologically active intact FGF23 (iFGF23) results in the formation of C-terminal fragments (cFGF23). An increase in cFGF23 relative to iFGF23 suppresses FGF receptor signaling by competitive inhibition. EPO lowers the i:cFGF23 ratio, thereby overcoming iFGF23-mediated suppression of erythropoiesis. We investigated EPO-FGF23 signaling and levels of erythroferrone (ERFE) in 90 patients with hereditary hemolytic anemia (www.trialregister.nl [NL5189]). We show, for the first time, the importance of EPO-FGF23 signaling in hereditary hemolytic anemia: there was a clear correlation between total FGF23 and EPO levels (r = +0.64; 95% confidence interval [CI], 0.09-0.89), which persisted after adjustment for iron load, inflammation, and kidney function. There was no correlation between iFGF23 and EPO. Data are consistent with a low i:cFGF23 ratio. Therefore, as expected, we report a correlation between EPO and ERFE in a diverse set of hereditary hemolytic anemias (r = +0.47; 95% CI, 0.14-0.69). There was no association between ERFE and total FGF23 or iFGF23, which suggests that ERFE does not contribute to the connection between FGF23 and EPO. These findings open a new area of research and might provide potentially new druggable targets with the opportunity to ameliorate ineffective erythropoiesis and the development of disease complications in hereditary hemolytic anemias

Low Urinary Creatinine Excretion Is Associated With Self-Reported Frailty in Patients With Advanced Chronic Kidney Disease

Frailty and muscle wasting, a component of frailty, are common in advanced stage chronic kidney disease (CKD). Whether frailty is associated with low urinary creatinine excretion (UCrE) as a measure of muscle mass in this population is unknown. Furthermore, reference values of UCrE are lacking. We first defined low UCrE and studied correlates of low UCrE, and subsequently studied cross-sectional associations of frailty with low UCrE in patients with advanced CKD. Methods: A total of 2748 healthy individuals of the general population-based PREVEND study were included to define low UCrE (UCrE indexed for height, below the age- and sex-specific 5th percentile of the distribution). Frailty was defined using a modification of the Fried frailty phenotype. In a CKD population that included 320 and 967 participants of the PREPARE-2 and NECOSAD studies, respectively, cross-sectional associations of self-reported frailty, the individual components that define self-reported frailty, and frailty-associated variables with low UCrE were evaluated using multivariate logistic and linear regression models. Results: Low UCrE was found in 38% of the CKD patients. A lower glomerular filtration rate was strongly associated with low UCrE. Self-reported frailty (adjusted odds ratio: 2.19; 95% confidence interval: 1.28−3.77) and the individual components were associated with low UCrE, independent of comorbidities. The frailty-associated variables hemoglobin and albumin were inversely associated with low UCrE, and parathyroid hormone was positively associated with low UCrE. Discussion: Lower kidney function is a strong correlate of low UCrE and self-reported frailty, and the individual frailty components are associated with low UCrE as well, independent of comorbidities