Iron Regulation by Molidustat, a Daily Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor, in Patients with Chronic Kidney Disease.

BACKGROUND/AIMS: The current treatment for anemia associated with chronic kidney disease (CKD) includes the administration of erythropoiesis stimulating agents (ESAs) combined with iron supplementation. Molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, has potential to treat anemia associated with CKD through increased erythropoietin production and improved iron availability. Here, we report the effect of molidustat on iron metabolism. METHOD: Parameters of iron metabolism were monitored in three 16-week, randomized, controlled, phase 2 studies assessing the safety and efficacy of molidustat in the treatment of anemia associated with CKD in different populations: treatment-naïve and previously ESA-treated patients not on dialysis, and previously ESA-treated patients on hemodialysis. Iron supplementation was left at the discretion of the investigator. RESULTS: In treatment-naïve patients not on dialysis, transferrin saturation (TSAT), hepcidin, ferritin, and iron concentrations decreased with molidustat, whereas total iron binding capacity (TIBC) increased. Similar results were observed in previously ESA-treated patients not on dialysis, although changes in those parameters were larger in treatment-naïve than in previously ESA-treated patients. In previously ESA-treated patients receiving hemodialysis, hepcidin concentration and TIBC remained stable with molidustat, whereas TSAT and ferritin and iron concentrations increased. Generally, similar trends were observed in secondary analyses of subgroups of patients not receiving iron supplementation. CONCLUSIONS: Molidustat is a potential alternative to standard treatment of anemia associated with CKD, with a different mechanism of action. In patients not receiving dialysis, molidustat increases iron availability. In patients receiving hemodialysis, further investigation is required to understand fully the mechanisms underlying iron mobilization associated with molidustat.

Low-voltage digital selenium radiography: detection of simulated interstitial lung disease, nodules, and catheters--a phantom study.

PURPOSE: To compare three tube voltages in digital selenium radiography for the detection of simulated interstitial lung disease, nodules, and catheters. MATERIALS AND METHODS: Simulated catheters, nodules, and ground-glass, linear, miliary, and reticular patterns were superimposed over an anthropomorphic chest phantom. Digital selenium radiography was performed with different tube voltages (70, 90, and 150 kVp). Hard-copy images were generated. Detection performance of five radiologists was compared by using receiver operating characteristic (ROC) analysis involving 54,000 observations. RESULTS: The detection of ground-glass, linear, miliary, and reticular patterns over lucent lung and of nodules equal to, smaller than, and larger than 10 mm increased when 70 kVp and/or 90 kVp was used. However, only the reticular pattern was significantly better detected at lower peak voltage (P <.05). Simulated catheters and nodules over the mediastinum showed smaller areas under the ROC curve at lower peak voltage. These results were not statistically significant (P >.05). CONCLUSION: The diagnostic performance of digital selenium radiography at lower peak voltage is at least as good as that at higher peak voltage for interstitial lung disease over lucent lung. Performance is equivalent for nodules and catheters over obscured chest regions at lower peak voltages compared with that at 150 kVp. Our results implicate that the use of high-voltage technique in digital selenium radiography should be reassessed.

Performance of a flat-panel detector in the detection of artificial erosive changes: comparison with conventional screen-film and storage-phosphor radiography.

The purpose of this study was to compare a large-area, direct-readout, flat-panel detector system with a conventional screen-film system, a storage-phosphor system, and a mammography screen-film system with regard to the detection of artificial bone erosions simulating rheumatoid disease, and to assess its diagnostic performance with decreasing exposure dose. Six hundred forty regions were defined in 160 metacarpophalangeal and proximal interphalangeal joint specimens from 20 monkey paws (4 regions per joint). Artificial bone erosions were created in 320 of these 640 regions. Specimens were enclosed in containers filled with water to obtain absorption and scatter radiation conditions similar to those of a human hand. Imaging was performed using a flat-panel system, a speed class 200 screen-film system, a mammography screen-film system, and a storage-phosphor system under exactly matched conditions. Different exposure doses equivalent to speed classes of S=100, 200, 400, 800, 1600, and 3200 were used. In all images the presence or absence of a lesion was assessed by three radiologists using a five-level confidence scale. Receiver operating characteristic (ROC) analysis was performed for a total of 21,120 observations (1920 for each imaging modality and exposure level) and diagnostic performance estimated by the area under the ROC curve (A(z)). The significance of differences in diagnostic performance was tested with analysis of variance. The ROC analysis showed A(z) values of 0.809 (S=200), 0.768 (S=400), 0.737 (S=800), 0.710 (S=1600), and 0.685 (S=3200) for the flat-panel system, 0.770 for the speed class 200 screen-film system, 0.781 (S=200), 0.739 (S=400), 0.724 (S=800), 0.680 (S=1600) for the storage-phosphor system, and 0.798 for the mammography screen-film system. Analysis of variance showed significant differences between different combinations of imaging modalities and exposure doses ( p<0.05). The diagnostic performance of the flat-panel detector system is superior to that of a screen-film system and a storage-phosphor system for the detection of erosive lesions at clinical exposure settings (S=200). Using the flat-panel system the exposure dose can be reduced by 50% to obtain a diagnostic performance comparable to a speed class 200 screen-film system.