Pretreatment serum FGF-23 levels predict the efficacy of calcitriol therapy in dialysis patients

Pretreatment serum FGF-23 levels predict the efficacy of calcitriol therapy in dialysis patients.BackgroundThe predictor for the result of calcitriol therapy would be useful in the clinical practice of secondary hyperparathyroidism. Fibroblast growth factor-23 (FGF-23) is a newly found circulating phosphaturic factor. Its circulating level is elevated in uremia.MethodsDialysis patients with plasma intact parathyroid hormone (iPTH) levels greater than 300 pg/mL were included in the study. Calcitriol was intravenously injected three times a week. The patients whose plasma iPTH levels dropped below 300 pg/mL within 24 weeks were defined as those who had been successfully treated. A sandwich enzyme-linked immunosorbent assay (ELISA) system that detects human FGF-23 was applied.ResultsSixty-two patients were analyzed. The pretreatment FGF-23 levels were related to the iPTH levels, calcium × phosphate product levels, and history of active vitamin D therapy. The pretreatment FGF-23, iPTH, and calcium levels were lower in the patients who would be successfully treated with calcitriol. A logistic regression study revealed that the pretreatment iPTH and FGF-23 levels significantly affected the therapy results. Analyses using a receiver-operated curve revealed that FGF-23 was the best screening test for identifying patients with future refractory response to calcitriol therapy. The treatment would be successful in 88.2% of those with FGF-23 ≤9860 ng/L and iPTH ≤591 pg/mL, while it would be successful in only 4.2% of those with FGF-23 >9860 ng/L and iPTH >591 pg/mL.ConclusionPretreatment serum FGF-23 levels were a good indicator in predicting the response to calcitriol therapy. The measurement of serum FGF-23 levels, especially in combination with iPTH levels, is a promising laboratory examination for the clinical practice of secondary hyperparathyroidism

Establishment of sandwich ELISA for soluble alpha-Klotho measurement: Age-dependent change of soluble alpha-Klotho levels in healthy subjects

Background α-Klotho (αKl) regulates mineral metabolism such as calcium ion (Ca2+) and inorganic phosphate (Pi) in circulation. Defects in mice result in clinical features resembling disorders found in human aging. Although the importance of transmembrane-type αKl has been demonstrated, less is known regarding the physiological importance of soluble-type αKl (sαKl) in circulation. Objectives The aims of this study were: (1) to establish a sandwich ELISA system enabling detection of circulating serum sαKl, and (2) to determine reference values for sαKl serum levels and relationship to indices of renal function, mineral metabolism, age and sex in healthy subjects. Results We successively developed an ELISA to measure serum sαKl in healthy volunteers (n = 142, males 66) of ages (61.1 ± 18.5 year). The levels (mean ± SD) in these healthy control adults were as follows: total calcium (Ca; 9.46 ± 0.41 mg/dL), Pi (3.63 ± 0.51 mg/dL), blood urea nitrogen (BUN; 15.7 ± 4.3 mg/dL), creatinine (Cre; 0.69 ± 0.14 mg/dL), 1,25 dihydroxyvitamin D (1,25(OH)2D; 54.8 ± 17.7 pg/mL), intact parathyroid hormone (iPTH; 49.2 ± 20.6 pg/mL), calcitonin (26.0 ± 12.3 pg/mL) and intact fibroblast growth factor (FGF23; 43.8 ± 17.6 pg/mL). Serum levels of sαKl ranged from 239 to 1266 pg/mL (mean ± SD; 562 ± 146 pg/mL) in normal adults. Although sαKl levels were not modified by gender or indices of mineral metabolism, sαKl levels were inversely related to Cre and age. However, sαKl levels in normal children (n = 39, males 23, mean ± SD; 7.1 ± 4.8 years) were significantly higher (mean ± SD; 952 ± 282 pg/mL) than those in adults (mean ± SD; 562 ± 146, P < 0.001). A multivariate linear regression analysis including children and adults in this study demonstrated that sαKl correlated negatively with age and Ca, and positively with Pi. Finally, we measured a serum sαKl from a patient with severe tumoral calcinosis derived from a homozygous missense mutation of α-klotho gene. In this patient, sαKl level was notably lower than those of age-matched controls. Conclusion We established a detection system to measure human serum sαKl for the first time. Age, Ca and Pi seem to influence serum sαKl levels in a normal population. This detection system should be an excellent tool for investigating sαKl functions in mineral metabolism

Inverse Optimization of Core Shape of Electromagnetic Devices using Genetic Algorithms

In this paper a new method for the inverse optimization of core shapes of electromagnetic devices using Genetic Algorithms is presented. For the generation of an initial population and its offspring, the available core area is directly encoded using binary technique. Two methods for selection of genes are proposed: non-restricted method and restricted method. Both methods are applied to the optimization of a metal mold cavity inside permanent magnet production equipment. Electromagnetic analysis is performed using the 2-D finite element method. The robustness of the Genetic Algorithm and the accuracy of the obtained results are very promising

Hybrid Method for Inverse Electromagnetic Coil Optimization Using Multi-transition and Hopfield Neural Networks

In this paper, a hybrid method for inverse optimization of electromagnetic coils utilizing the multi-transition neural network and the Hopfield neural network is proposed. Due to the discrete character of the neural network, an optimization problem is transformed into a discrete problem through the division of the entire coil area into elemental coils with constant current density. The minimization of the objective function is performed by the multi-transition neural network and the Hopfield neural network in turns. Subdivision of the elemental coils is performed in order to achieved better accuracy of the results which are verified using 2-D finite element analysis. The application of the proposed method for inverse optimization of MRI device is also presented