Mechanism of Action and Clinical Attributes of Auryxia® (Ferric Citrate).

Chronic kidney disease (CKD) is a major cause of morbidity and premature mortality and represents a significant global public health issue. Underlying this burden are the many complications of CKD, including mineral and bone disorders, anemia, and accelerated cardiovascular disease. Hyperphosphatemia and elevated levels of fibroblast growth factor 23 (FGF23) have been identified as key independent risk factors for the adverse cardiovascular outcomes that frequently occur in patients with CKD. Auryxia® (ferric citrate; Keryx Biopharmaceuticals, Inc., Boston, MA, USA) is an iron-based compound with distinctive chemical characteristics and a mechanism of action that render it dually effective as a therapy in patients with CKD; it has been approved as a phosphate binder for the control of serum phosphate levels in adult CKD patients treated with dialysis and as an iron replacement product for the treatment of iron deficiency anemia in adult CKD patients not treated with dialysis. This review focuses on Auryxia, its mechanism of action, and the clinical attributes that differentiate it from other, non-pharmaceutical-grade, commercially available forms of ferric citrate and from other commonly used phosphate binder and iron supplement therapies for patients with CKD. Consistent with the chemistry and mechanism of action of Auryxia, multiple clinical studies have demonstrated its efficacy in both lowering serum phosphate levels and improving iron parameters in patients with CKD. Levels of FGF23 decrease significantly with Auryxia treatment, but the effects associated with the cardiovascular system remain to be evaluated in longer-term studies

Mechanism of Action and Clinical Attributes of Auryxia® (Ferric Citrate).

Chronic kidney disease (CKD) is a major cause of morbidity and premature mortality and represents a significant global public health issue. Underlying this burden are the many complications of CKD, including mineral and bone disorders, anemia, and accelerated cardiovascular disease. Hyperphosphatemia and elevated levels of fibroblast growth factor 23 (FGF23) have been identified as key independent risk factors for the adverse cardiovascular outcomes that frequently occur in patients with CKD. Auryxia® (ferric citrate; Keryx Biopharmaceuticals, Inc., Boston, MA, USA) is an iron-based compound with distinctive chemical characteristics and a mechanism of action that render it dually effective as a therapy in patients with CKD; it has been approved as a phosphate binder for the control of serum phosphate levels in adult CKD patients treated with dialysis and as an iron replacement product for the treatment of iron deficiency anemia in adult CKD patients not treated with dialysis. This review focuses on Auryxia, its mechanism of action, and the clinical attributes that differentiate it from other, non-pharmaceutical-grade, commercially available forms of ferric citrate and from other commonly used phosphate binder and iron supplement therapies for patients with CKD. Consistent with the chemistry and mechanism of action of Auryxia, multiple clinical studies have demonstrated its efficacy in both lowering serum phosphate levels and improving iron parameters in patients with CKD. Levels of FGF23 decrease significantly with Auryxia treatment, but the effects associated with the cardiovascular system remain to be evaluated in longer-term studies

Formation of Carbon–Carbon Triply Bonded Molecules from Two Free Carbyne Radicals via a Conical Intersection

The recent proposal (Bogoslavsky, B.; Levy, O.; Kotlyar, A.; Salem, M.; Gelman, F.; Bino, A. <i>Angew. Chem., Int. Ed.</i> <b>2012</b>, <i>51</i>, 90–94) that metallo–alkylidyne complexes decompose in aqueous solution and give rise to free carbynes, which couple to yield acetylenes, is examined here theoretically. On the basis of the known marker reactions of carbynes in the doublet and quartet state, it is concluded that most of the reactivity patterns observed in the Bino experiment arose from quartet carbynes. Indeed, theory shows that quartet carbynes can be funneled to acetylene via a conical intersection. Moreover, many of the minor products are also identified as markers of the quartet carbynes. Carbynes formation in their doublet state is a minor channel that branches from the conical intersection and leads to the formation of dienes and olefins in the Bino experiment. Thus, we show that conical intersections are important also in thermally initiated reactions. Coupled to the experimental approach, the study opens a window to studies of carbynes under mild conditions