China
Africa
Explore chapters and articles related to this topic
Optical Angiography at Diabetes
Published in Andrey V. Dunaev, Valery V. Tuchin, Biomedical Photonics for Diabetes Research, 2023
Dan Zhu, Jingtan Zhu, Dongyu Li, Tingting Yu, Wei Feng, Rui Shi
Hasegawa et al. utilized T1D rat and mouse models induced by STZ or alloxan and CUBIC-kidney clearing protocol to clarify the net effects of HIF stabilization on energy metabolism in diabetic kidney [12]. They also performed comprehensive 3D analysis to visualize glomeruli in the kidney using anti-podocin antibodies. They found that renal pathological abnormalities (glomerulomegaly and GBM thickening) induced by diabetes in the early stages of DN could be mitigated by enarodustat treatment.
Elucidation of clearance mechanism of TP0463518, a novel hypoxia-inducible factor prolyl hydroxylase inhibitor: does a species difference in excretion routes exist between humans and animals?
Published in Xenobiotica, 2022
Hiroki Takano, Akiko Mizuno-Yasuhira, Jun-ichi Yamaguchi, Hiromi Endo
Anaemia has been a globally reported complication in patients with chronic kidney disease (CKD) (Kassebaum et al. 2014). A decrease in kidney function followed by the reduced production of erythropoietin (EPO) usually causes anaemia (McGonigle et al. 1984). Recently, more attention has been paid to hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) inhibitors as novel therapeutic agents for treating anaemia in patients with CKD (Souza et al. 2020). Between 2019 and 2021, roxadustat, daprodustat, vadadustat, enarodustat, and molidustat were approved in Japan for the treatment of anaemia in CKD patients. HIF has been regarded as the most important transcriptional factor activated by hypoxia (Mole et al. 2009; Semenza 2011), playing a central role in the regulation of many target genes including those involved in EPO production. HIF is composed of an oxygen-regulated HIF-α subunit and a constitutively expressed HIF-β subunit. Under a normoxia condition, cellular HIF-α is rapidly hydroxylated in the cytoplasm by HIF-PH (Ivan et al. 2001; Jaakkola et al. 2001), which are nonheme, iron-containing enzymes that hydroxylate the proline residues of HIF-α, leading to proteasomal degradation. Thus, HIF-PH inhibitors enable HIF stabilisation followed by EPO production, leading to therapeutic efficacy for in CKD patients with anaemia (Rabinowitz 2013).
Effect of hypoxia-inducible factor-prolyl hydroxylase inhibitors on anemia in patients with CKD: a meta-analysis of randomized controlled trials including 2804 patients
Published in Renal Failure, 2020
Bin Wang, Qing Yin, Yu-Chen Han, Min Wu, Zuo-Lin Li, Yan Tu, Le-ting Zhou, Qing Wei, Hong Liu, Ri-Ning Tang, Jing-Yuan Cao, Lin-Li Lv, Bi-Cheng Liu
Both exclusion and inclusion criteria were prespecified. RCT studies must meet several criteria. Firstly, the population is patients with CKD or dialysis patients whose age is > 18 years old. Secondly, intervention: treatment with HIF-PHIs (Roxadustat, Vadadustat, Daprodustat, Molidustat, Enarodustat, Desidustat, and DS-1093a) regardless of dose and duration. Thirdly, the primary outcome was Hb CFB, and the secondary outcomes included the mean change in the hepcidin, ferritin, transferrin, total iron-binding capacity (TIBC), TSAT and serum iron and the occurrence of each adverse event (hypertension, hyperkalemia, cardiovascular events, vascular access thrombosis, headache, vomiting, nasopharyngitis, nausea, and diarrhea).
Hepcidin as a therapeutic target for anemia and inflammation associated with chronic kidney disease
Published in Expert Opinion on Therapeutic Targets, 2019
Jolanta Malyszko, Jacek S. Malyszko, Joanna Matuszkiewicz-Rowinska
Hypoxia is known to influence erythropoietin gene expression. This is the accepted paradigm of oxygen-regulated gene expression. Hypoxia-inducible factors (HIFs), HIF-1 and HIF-2 were discovered and described by Semenza in 2011 [116] He elegantly showed that HIFs are the part of the common oxygen-sensing pathway regulating changes in oxygen supply in higher organisms. HIFs are built of one of 2 oxygen-regulated α-subunits (HIF-1α and HIF-2α) which together with constitutive HIF-β subunit make heterodimers. There are three HIF α regulated by a family of three enzymes, the HIF prolyl hydroxylases (also known as prolyl hydroxylase domain-containing protein 1–3, PHD1–3 or C. elegans EGL9 homolog 1–3, EGLN1–3) [117,118]. PHD2–HIF-2α axis controls EPO gene expression in the kidney, in particular, regulation of erythropoietin is regulated by HIF-2α isoform. HIF-α stability and transcriptional activity are under the control of molecular oxygen. The hepcidin promoter contains several binding sites for HIF, and it is possible that the mechanisms of hypoxic regulation of hepcidin will turn out to be transcriptional, via the common oxygen-sensing regulatory pathway [52]. STAT, the hepatocyte nuclear factor 4 and C/EBP (enhancer binding proteins which control proliferation and differentiation of various cells) are also present on the hepcidin gene promoter [119]. HIF stabilization by prolyl hydroxylation inhibition provides a novel therapeutic possibility to anemia treatment based on mimicking the hypoxia-driven expression of endogenous EPO in the kidney thus enhancing its synthesis [120,121]. HIF stabilizers (roxadustat, vadadustat, molidustat, daprodustat, enarodustat) are now in phase III clinical trials.