Review
Medicine, General & Internal
Tomas Ganz, Francesco Locatelli, Mustafa Arici, Tadao Akizawa, Michael Reusch
Summary: Roxadustat has a distinct impact on iron parameters and hemoglobin levels compared to erythropoiesis-stimulating agents (ESAs). It decreases serum ferritin levels to a greater extent and increases serum iron levels instead of decreasing them. The decrease in transferrin saturation in patients treated with Roxadustat is relatively small and is not observed in non-dialysis or dialysis-dependent chronic kidney disease (CKD) patients by Week 52. Roxadustat improves iron availability, increases erythropoiesis, and requires less intravenous iron use compared to placebo and ESA. Hepcidin levels generally decrease more significantly with Roxadustat than with ESA or placebo. The mechanisms underlying the effects of Roxadustat and ESAs on iron availability, stores, and erythropoiesis differ and should be considered holistically when treating CKD anemia.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Medicine, General & Internal
Hirotaka Fukasawa, Ryuichi Furuya, Mai Kaneko, Daisuke Nakagami, Yuri Ishino, Shuhei Kitamoto, Kyosuke Omata, Hideo Yasuda
Summary: Zinc is essential for various physiological processes in humans, and its deficiency can lead to impaired growth, immune function, taste maintenance, and neurological function. Patients with chronic kidney disease are at risk of zinc deficiency, which is associated with anemia, nutritional problems, cardiovascular diseases, and non-specific symptoms. Zinc supplementation may be beneficial, but it can cause copper deficiency and severe disorders. This review focuses on the roles of zinc and its association with complications in CKD patients.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Cell Biology
Eya Hamza, Mercedes Vallejo-Mudarra, Hakim Ouled-Haddou, Cristina Garcia-Caballero, Melania Guerrero-Hue, Laure Santier, Sandra Rayego-Mateos, Islam Amine Larabi, Jean -Claude Alvarez, Loic Garcon, Ziad A. Massy, Gabriel Choukroun, Juan Antonio Moreno, Laurent Metzinger, Valerie Metzinger-Le Meuth
Summary: Chronic kidney disease (CKD) is a global health condition characterized by a progressive deterioration of kidney function. Uremic toxins, such as Indoxyl Sulfate (IS), are associated with CKD-related complications, including anemia. Our study investigated the impact of IS on erythropoiesis in CKD patients, and found that IS can induce apoptosis and hinder the differentiation of erythroid progenitor cells. Additionally, IS deregulated the expression of erythropoietic-related genes. These findings suggest that IS may contribute to the development of anemia in CKD.
CELLULAR SIGNALLING
(2023)
Article
Medicine, General & Internal
Keiji Hirai, Shohei Kaneko, Saori Minato, Katsunori Yanai, Momoko Hirata, Taisuke Kitano, Kiyonori Ito, Yuichiro Ueda, Susumu Ookawara, Yoshiyuki Morishita
Summary: This study aimed to determine the effects of roxadustat on anemia, iron metabolism, renal function, proteinuria, and lipid metabolism in non-dialysis CKD patients. After switching from erythropoietin-stimulating agent (ESA) to roxadustat, the roxadustat group showed significantly higher hemoglobin concentration and lower levels of total cholesterol, LDL-C, HDL-C, and triglycerides compared to the ESA group. Regression analysis further revealed that the initial dose of roxadustat was correlated with changes in hemoglobin levels during the first 4 weeks of treatment, while age and the dose of roxadustat at 24 weeks were correlated with hemoglobin concentration after 24 weeks of administration.
FRONTIERS IN MEDICINE
(2023)
Article
Medicine, General & Internal
Jina Lim, Chung Jo Yu, Hoon Yu, Sang Jin Ha
Summary: The study showed that ESA can improve endothelial dysfunction, left ventricular hypertrophy, and left atrial volume in patients with non-dialysis CKD. This suggests that ESA may be considered as adjunctive therapy for reducing cardiovascular risk in these patients.
Letter
Medicine, General & Internal
H. Franklin Bunn
Summary: The trials show convincing evidence that vadadustat is effective in treating anemia in patients with chronic kidney disease, compared to darbepoetin alfa which has prolonged life span in circulation.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Peng Xu, Raymond S. M. Wong, Wojciech Krzyzanski, Xiaoyu Yan
Summary: The hormone erythroferrone (ERFE) may serve as a predictive factor for erythropoiesis, with its dynamics showing a correlation with the erythropoietic effects of erythropoiesis-stimulating agents (ESAs) treatment. The early increase of ERFE levels appears to be a predictor of the hemoglobin response.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Urology & Nephrology
Violante Olivari, Simona Maria Di Modica, Maria Rosa Lidonnici, Mariam Aghajan, Celia Cordero-Sanchez, Emanuele Tanzi, Mariateresa Pettinato, Alessia Pagani, Francesca Tiboni, Laura Silvestri, Shuling Guo, Giuliana Ferrari, Antonella Nai
Summary: Anemia, a common complication of systemic inflammation, is influenced by cytokines, hepatic hormone, and iron metabolism. Anemia of chronic kidney disease (CKD) is a distinct form of inflammatory anemia, and traditional therapy based on increased erythropoietin (EPO) is limited. Hematopoietic and hepatic targeting of transferrin receptor 2 (Tfr2) can improve anemia by promoting erythropoiesis and increasing iron supply. Thus, combined targeting of hematopoietic and hepatic Tfr2 may be a potential therapeutic option.
KIDNEY INTERNATIONAL
(2023)
Article
Urology & Nephrology
Tadao Akizawa, Keiko Tanaka-Amino, Tetsuro Otsuka, Yusuke Yamaguchi
Summary: This analysis evaluated dosing trends of roxadustat and darbepoetin alfa required to maintain target hemoglobin concentrations in Japanese NDD CKD patients with risk factors associated with ESA hyporesponsiveness, finding higher doses needed in patients with higher ESA resistance index.
AMERICAN JOURNAL OF NEPHROLOGY
(2021)
Article
Medicine, Research & Experimental
Jonathan Barratt, Frank Dellanna, Jose Portoles, Gabriel Choukroun, Luca De Nicola, James Young, Nada Dimkovic, Michael Reusch
Summary: This study aimed to investigate the safety of roxadustat compared with erythropoiesis-stimulating agents (ESA) in non-dialysis-dependent (NDD) or incident dialysis-dependent (ID-DD) chronic kidney disease (CKD) patients with anemia. The results showed that roxadustat was comparable to ESA in terms of major adverse cardiovascular events (MACE), all-cause mortality, and treatment-emergent adverse events (TEAEs). There was no evidence of increased risk of cardiovascular events or mortality with roxadustat.
ADVANCES IN THERAPY
(2023)
Article
Urology & Nephrology
Minoru Yasukawa, Shigeyuki Arai, Michito Nagura, Ryo Kido, Shinichiro Asakawa, Daigoro Hirohama, Osamu Yamazaki, Yoshifuru Tamura, Michitaka Fujimaki, Sawako Kobayashi, Masakazu Mimaki, Hiroko Kodama, Shunya Uchida, Yoshihide Fujigaki, Shigeru Shibata
Summary: This study found that serum selenium levels are significantly associated with ESA responsiveness and can predict ESA resistance independently of iron status. The association of low serum selenium with ESA hyporesponsiveness persisted after adjustment of confounding variables.
KIDNEY INTERNATIONAL REPORTS
(2022)
Review
Medicine, General & Internal
Jose Portoles, Leyre Martin, Jose Jesus Broseta, Aleix Cases
Summary: Anemia is a common complication in chronic kidney disease (CKD) and is managed with iron supplements and erythropoiesis stimulating agents. Advances in treatment, such as the development of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) and insights from recent clinical trials on iron supplementation, may change future treatment targets.
FRONTIERS IN MEDICINE
(2021)
Article
Nutrition & Dietetics
Meijuan Bai, Peijuan Cao, Yijun Lin, Pengcheng Yu, Shuo Song, Lingling Chen, Lan Wang, Yan Chen
Summary: Short-term caloric restriction (CR) promotes erythropoiesis and ameliorates phenylhydrazine-induced acute anemia.
FRONTIERS IN NUTRITION
(2022)
Article
Endocrinology & Metabolism
Joao Victor Salgado, Miguel Angelo Goes, Natalino Salgado Filho
Summary: The global nephrology community acknowledges the increasing burden of kidney disease and emphasizes on early diagnosis, understanding of disease progression, and development of new therapeutic interventions. FGF21 is considered a key regulator of lipid, glucose, and energy metabolism, as well as stress responses. While promising results have been shown with FGF21 analogs in metabolic disease, its exact role in kidney function remains poorly understood.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2021)
Article
Medicine, General & Internal
Yoshimasa Kokado, Manabu Ishii, Kiichiro Ueta, Hiroyuki Yamamoto, Hiraku Kumamaru, Masaaki Isshiki, Sven Demiya, Hiroaki Miyata
Summary: This study evaluated hemoglobin levels at the initiation of erythropoiesis stimulating agent (ESA) therapy in patients with non-dialysis-dependent chronic kidney disease (CKD) and anemia using a large-scale administrative database in Japan. The study found that many patients had hemoglobin levels lower than the recommended levels by the Japanese treatment guidelines at the start of ESA therapy.
CURRENT MEDICAL RESEARCH AND OPINION
(2022)
Article
Biochemistry & Molecular Biology
Michael Ramek, Jasmina Sabolovic
Summary: This paper investigates the geometries, energy landscapes, and magnetic parameters of copper(II) amino acid compounds using density functional theory calculations. The results show that certain conformers with histaminate-like and glycine-like modes have low Gibbs free energies and high metal-binding affinities. The predicted conformations reproduce the experimental electron paramagnetic resonance parameters.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Wei Tian, Wen Zhong, Zengyan Yang, Ling Chen, Shijie Lin, Yanping Li, Yuxing Wang, Peilin Yang, Xing Long
Summary: A series of novel dibutyltin complexes based on salen-like ligands were synthesized and characterized. Complex S03 showed excellent in vitro anticancer activity and induced cancer cell death through multiple mechanisms. This study reveals new mechanisms of organotin complexes and provides new insights into the development of organotin metal complexes as anticancer drugs.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Natalie C. Korkola, Martin J. Stillman
Summary: Many proteins require a metal cofactor for their function, and these metals play a role in protein folding. The study found that the metallation rates of different metal binding pathways are influenced by pH, with the less cooperative pathway being more affected by low pH conditions. Specific mixtures of structures are formed in the initial steps of metallation, and unfolding the disordered apo-MT structure hinders the formation of these preliminary structures. The compact conformation of the native apo-MT allows for rapid formation of metal-thiolate structures with high affinity, providing protection from oxidation.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Boxuan Yang, Xitong Song, Binju Wang
Summary: The diiron active site plays a crucial role in catalytic transformations in both biological and chemical systems. Recent advancements in the field include the synthesis of biomimetic diiron catalysts inspired by the active structure of soluble methane monooxygenase (sMMO), which have been successfully applied to the dehydrogenation of indolines.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Christina N. Banti, Angeliki A. Piperoudi, Catherine P. Raptopoulou, Vassilis Psycharis, Constantinos M. Athanassopoulos, Sotiris K. Hadjikakou
Summary: Two copper(I) polymorphs with mitochondria-targeting properties were successfully prepared via metal ion conjugation. These compounds showed promising activities in DNA binding, enzyme inhibition, and cancer cell inhibition. The molecular mechanisms of action were investigated.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2024)