Browsing by Author "Ganz, Tomas"

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    Erythropoietic effects of vadadustat in patients with anemia associated with chronic kidney disease
    (Wiley, 2022) Koury, Mark J.; Agarwal, Rajiv; Chertow, Glenn M.; Eckardt, Kai-Uwe; Fishbane, Steven; Ganz, Tomas; Haase, Volker H.; Hanudel, Mark R.; Parfrey, Patrick S.; Pergola, Pablo E.; Roy-Chaudhury, Prabir; Tumlin, James A.; Anders, Robert; Farag, Youssef M.K.; Luo, Wenli; Minga, Todd; Solinsky, Christine; Vargo, Dennis L.; Winkelmayer, Wolfgang C.; Medicine, School of Medicine
    Patients with chronic kidney disease (CKD) develop anemia largely because of inappropriately low erythropoietin (EPO) production and insufficient iron available to erythroid precursors. In four phase 3, randomized, open-label, clinical trials in dialysis-dependent and non-dialysis-dependent patients with CKD and anemia, the hypoxia-inducible factor prolyl hydroxylase inhibitor, vadadustat, was noninferior to the erythropoiesis-stimulating agent, darbepoetin alfa, in increasing and maintaining target hemoglobin concentrations. In these trials, vadadustat increased the concentrations of serum EPO, the numbers of circulating erythrocytes, and the numbers of circulating reticulocytes. Achieved hemoglobin concentrations were similar in patients treated with either vadadustat or darbepoetin alfa, but compared with patients receiving darbepoetin alfa, those receiving vadadustat had erythrocytes with increased mean corpuscular volume and mean corpuscular hemoglobin, while the red cell distribution width was decreased. Increased serum transferrin concentrations, as measured by total iron-binding capacity, combined with stable serum iron concentrations, resulted in decreased transferrin saturation in patients randomized to vadadustat compared with patients randomized to darbepoetin alfa. The decreases in transferrin saturation were associated with relatively greater declines in serum hepcidin and ferritin in patients receiving vadadustat compared with those receiving darbepoetin alfa. These results for serum transferrin saturation, hepcidin, ferritin, and erythrocyte indices were consistent with improved iron availability in the patients receiving vadadustat. Thus, overall, vadadustat had beneficial effects on three aspects of erythropoiesis in patients with anemia associated with CKD: increased endogenous EPO production, improved iron availability to erythroid cells, and increased reticulocytes in the circulation.
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    Erythropoietin stimulates murine and human fibroblast growth factor-23, revealing novel roles for bone and bone marrow
    (Ferrata Storti Foundation, 2017-11) Clinkenbeard, Erica L.; Hanudel, Mark R.; Stayrook, Keith R.; Appaiah, Hitesh Nidumanda; Farrow, Emily G.; Cass, Taryn A.; Summers, Lelia J.; Ip, Colin S.; Hum, Julia M.; Thomas, Joseph C.; Ivan, Mircea; Richine, Briana M.; Chan, Rebecca J.; Clemens, Thomas L.; Schipani, Ernestina; Sabbagh, Yves; Xu, Linlin; Srour, Edward F.; Alvarez, Marta B.; Kacena, Melissa A.; Salusky, Isidro B.; Ganz, Tomas; Nemeth, Elizabeta; White, Kenneth E.; Medical and Molecular Genetics, School of Medicine
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    Iron Administration, Infection, and Anemia Management in CKD: Untangling the Effects of Intravenous Iron Therapy on Immunity and Infection Risk
    (Elsevier, 2020-03-27) Ganz, Tomas; Aronoff, George R.; Gaillard, Carlo A. J. M.; Goodnough, Lawrence T.; Macdougall, Iain C.; Mayer, Gert; Porto, Graça; Winkelmayer, Wolfgang C.; Wish, Jay B.; Medicine, School of Medicine
    dysfunction, increased exposure to infectious agents, loss of cutaneous barriers, comorbid conditions, and treatment-related factors (eg, hemodialysis and immunosuppressant therapy). Because iron plays a vital role in pathogen reproduction and host immunity, it is biologically plausible that intravenous iron therapy and/or iron deficiency influence infection risk in CKD. Available data from preclinical experiments, observational studies, and randomized controlled trials are summarized to explore the interplay between intravenous iron and infection risk among patients with CKD, particularly those receiving maintenance hemodialysis. The current evidence base, including data from a recent randomized controlled trial, suggests that proactive judicious use of intravenous iron (in a manner that minimizes the accumulation of non–transferrin-bound iron) beneficially replaces iron stores while avoiding a clinically relevant effect on infection risk. In the absence of an urgent clinical need, intravenous iron therapy should be avoided in patients with active infection. Although serum ferritin concentration and transferrin saturation can help guide clinical decision making about intravenous iron therapy, definition of an optimal iron status and its precise determination in individual patients remain clinically challenging in CKD and warrant additional study.