A 71-year-old man with a 20-year history of grade 3 hypertension experienced kidney dysfunction 2 years earlier. His serum creatinine (SCr) at the time was 140 μmol/L [with estimated glomerular filtration rate (eGFR) of 43.9 ml/min per 1.73m2], for which he received irbesartan since. At initial presentation, the spot urine dipstick protein was 1+, with an albumin-to-creatinine ratio of 230 mg/g (0-30) and normal urine sediments. The SCr was 176 μmol/L (eGFR = 32.8 ml/min per 1.73m2). The hemoglobulin (Hb) level decreased from 102 to 96 g/L despite oral ferrous succinate 100 mg twice daily starting 2 months ago. Roxadustat (ROXA) 50 mg (body weight, 70 kg) three times weekly was then prescribed. Unfortunately, the patient mistakenly took the drug at 50 mg three times a day (i.e., 1,050 mg instead of the intended 150 mg per week), which was 3.5 times the recommended starting dose for non-dialysis-dependent chronic kidney disease (CKD) patients (100 mg three times weekly for body weight >60 kg) and two times the highest drug manual-recommended weekly dose (2.5 mg/kg three times weekly) approved in the country. When the attending nephrologist discovered the misuse 1 month later, the patient reported no apparent discomfort, and his home blood pressure was in the range 110-130/60-80 mmHg. Repeat blood tests showed that the Hb increased from 96 to 163 g/L and the SCr from 199 to 201 μmol/L in a month. The serum alanine transaminase (ALT) remained within the normal range (from 12 U/L at baseline to 20 U/L), while the serum total and indirect bilirubin levels were slightly elevated. ROXA was withheld immediately. In 30 days, the serum bilirubin returned to baseline, but the Hb decreased from 163 to 140 g/L, and then to 108 g/L after 3 months. On the other hand, the SCr increased from 179 to 203 μmol/L. At 9 months after the initial dosing, when the SCr increased to 256 μmol/L and the Hb decreased to 94 g/L again, ROXA 50 mg three times weekly was reinitiated uneventfully. Herein, by introducing a case who erroneously consumed twice the highest recommended dose of ROXA for a month, but had apparently no obvious discomfort or unfavorable consequence, we attempt to provide a brief overview of the mechanism of action, characteristics, drug metabolism, and side effect profile associated with this agent.

Background: Roxadustat is commonly used to treat renal anemia. However, the potential effects of roxadustat on metabolism and organs other than the kidneys have recently attracted increased attention. Objective: This study aimed to examine the regulatory effects of roxadustat on thyroid hormones and blood lipid metabolism in patients with end-stage kidney disease (ESKD) undergoing hemodialysis. Methods: Eighty ESKD patients on hemodialysis and taking roxadustat were enrolled. Hemoglobin, thyroid hormones (TSH, FT3, FT4), and blood lipid profiles (TC, LDL-C, TG, HDL-C) were assessed before and after treatment. Changes in these parameters were compared, and relevant causative factors were analyzed. Results: Roxadustat significantly increased Hb, lowered TSH, FT4, TC, and LDL-C levels (all P<0.001). Patients were categorized into three groups based on post-treatment TSH inhibition percentage: Q1(≥70%), Q2(30%-70%), Q3(≤30%). Pre-treatment TSH decreased with reduced TSH inhibition (P<0.05). Post-treatment, TC, LDL-C, TSH, FT3, and FT4 increased with reduced TSH inhibition (all P<0.05).TC and LDL-C significantly decreased post-treatment in Q1 and Q2 (P<0.05). Correlation analysis showed a positive correlation between ΔTSH and pre-treatment TSH levels (r=0.732, P<0.001). The proportion of patients with ≥70% TSH inhibition increased with higher pre-treatment TSH levels (P for trend <0.05). ΔLDL-C and ΔTSH were positively correlated (r=0.278, P<0.05), with ΔTSH identified as an influencing factor in multiple linear regression (β=0.133, 95% CI [0.042, 0.223], P<0.05). Conclusion: Roxadustat effectively improves anemia in ESKD patients while inhibiting TSH and FT4 secretion and reducing TC and LDL-C levels. Decreases in TSH levels correlate with baseline TSH levels, and lowered blood lipid levels are associated with decreased TSH levels.

UNASSIGNED: Erythropoietin resistance is present in some patients with chronic kidney disease, especially in those undergoing hemodialysis, and is often treated using roxadustat rather than iron supplements and erythropoiesis-stimulating agents (ESAs). However, some patients cannot afford full doses of roxadustat. This retrospective study investigated the efficacy of low-dose roxadustat combined with recombinant human erythropoietin (rhuEPO) therapy in 39 patients with erythropoietin-resistant renal anemia undergoing maintenance hemodialysis (3-4 sessions/week).
UNASSIGNED: The ability of the combination of low-dose roxadustat and rhuEPO to increase the hemoglobin concentration over 12 weeks was assessed. Markers of iron metabolism were evaluated. Eligible adults received 50-60% of the recommended dose of roxadustat and higher doses of rhuEPO.
UNASSIGNED: The mean hemoglobin level increased from 77.67 ± 11.18 g/dL to 92.0 ± 8.35 g/dL after treatment, and the hemoglobin response rate increased to 72%. The mean hematocrit level significantly increased from 24.26 ± 3.99% to 30.04 ± 3.69%. The soluble transferrin receptor level increased (27.29 ± 13.60 mg/L to 38.09 ± 12.78 mg/L), while the total iron binding capacity (49.22 ± 11.29 mg/L to 43.91 ± 12.88 mg/L) and ferritin level (171.05 ± 54.75 ng/mL to 140.83 ± 42.03 ng/mL) decreased.
UNASSIGNED: Therefore, in patients with ESA-resistant anemia who are undergoing hemodialysis, the combination of low-dose roxadustat and rhuEPO effectively improves renal anemia and iron metabolism.

The introduction of hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors in Japan in 2019 for treating renal anemia in hemodialysis patients has resulted in an adverse event: central hypothyroidism. Although this adverse event was not widely recognized by the public, it was first documented in Japan in 2021. Despite limited case reports on roxadustat, an oral HIF-PH inhibitor that induces central hypothyroidism, this condition typically improves rapidly upon discontinuation of the drug. In this report, we present rare cases of roxadustat-induced central hypothyroidism in two patients: a woman in her 80s and a man in his 60s, neither of whom had prior thyroid disease. Both patients developed central hypothyroidism shortly after starting roxadustat treatment for renal anemia associated with antineutrophil cytoplasmic antibody-related vasculitis. Notably, neither patient had pituitary tumors or other pituitary hormone disorders. Thyroid function improved with levothyroxine treatment, even when oral roxadustat was continued. Roxadustat may induce central hypothyroidism, highlighting the importance of regularly measuring and evaluating thyroid function when administering this drug to monitor possible changes in thyroid hormone levels.

Renal anemia is generally caused by a decrease in the production of erythropoietin in kidney due to renal dysfunction, and this may be associated with the increase in mortality and cardiovascular events in addition to subjective symptoms such as fatigue and wobbliness. We report a case of an 87-year-old man with type 2 diabetes, hypertension, and dyslipidemia who had received roxadustat (a hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) inhibitor) for renal anemia due to diabetic nephropathy and in whom roxadustat was switched to daprodustat (another HIF-PH inhibitor) due to the onset of central hypothyroidism. About three weeks after this change, the patient developed acute asymptomatic cerebral infarction with an elevation of hemoglobin (Hb). It is unclear if the change to daprodustat was involved in the onset of cerebral infarction. However, this case suggests that particular caution should be paid to unexpected acute elevation of Hb after a change from one HIF-PH inhibitor to another, especially in a patient at high risk for cardiovascular events.

UNASSIGNED: This study compares the cardiovascular risk in anemic chronic kidney disease patients treated with Roxadustat versus erythropoietin stimulating agents (ESAs). It also explores the cardiovascular impact of Roxadustat.
UNASSIGNED: We searched PubMed, EMBASE, Cochrane, Scopus, and Web of Science databases up to 13 August 2023, using terms such as \"ESA,\" \"Roxadustat,\" \"MACE,\" \"stroke,\" \"death,\" \"myocardial infarction,\" and \"heart failure.\" Two researchers independently selected and extracted data based on predefined criteria. We assessed the risk of bias with the Cochrane tool and analyzed statistical heterogeneity using the Q and I2 tests. We conducted subgroup analyses by geographical region and performed data analysis with Stata 14.0 and RevMan 5.4 software. Data were sourced from the NCBI database by filtering for \"Roxadustat\" and \"human,\" and differentially expressed genes were identified using R software, setting the significance at p < 0.01 and a 2-fold logFC, followed by GO enrichment analysis, KEGG pathway analysis, and protein interaction network analysis.
UNASSIGNED: A total of 15 articles encompassing 1,43,065 patients were analyzed, including 1,38,739 patients treated with ESA and 4,326 patients treated with Roxadustat. In the overall population meta-analysis, the incidences of Major Adverse Cardiovascular Events (MACE), death, and heart failure (HF) were 13%, 8%, and 4% in the Roxadustat group, compared to 17%, 12%, and 6% in the ESA group, respectively, with P-values greater than 0.05. In the subgroup analysis, the incidences were 13%, 11%, and 4% for the Roxadustat group versus 17%, 15%, and 5% for the ESA group, also with p-values greater than 0.05. Bioinformatics analysis identified 59 differentially expressed genes, mainly involved in the inflammatory response. GO enrichment analysis revealed that these genes are primarily related to integrin binding. The main pathways identified were the TNF signaling pathway, NF-κB signaling pathway, and lipid metabolism related to atherosclerosis. The protein interaction network highlighted IL1B, CXCL8, ICAM1, CCL2, and CCL5 as the top five significantly different genes, all involved in the inflammatory response and downregulated by Roxadustat, suggesting a potential role in reducing inflammation.
UNASSIGNED: The meta-analysis suggests that the use of Roxadustat and ESA in treating anemia associated with chronic kidney disease does not significantly alter the likelihood of cardiovascular events in the overall and American populations. However, Roxadustat exhibited a safer profile with respect to MACE, death, and heart failure. The bioinformatics findings suggest that Roxadustat may influence integrin adhesion and affect the TNF and NF-κB signaling pathways, along with lipid and atherosclerosis pathways, potentially reducing inflammation.

Repairing multiphasic defects is cumbersome. This study presents new soft and hard scaffold designs aimed at facilitating the regeneration of multiphasic defects by enhancing angiogenesis and improving cell attachment. Here, the nonimmunogenic, nontoxic, and cost-effective human serum albumin (HSA) fibril (HSA-F) was used to fabricate thermostable (up to 90 °C) and hard printable polymers. Additionally, using a 10.0 mg/mL HSA-F, an innovative hydrogel was synthesized in a mixture with 2.0% chitosan-conjugated arginine, which can gel in a cell-friendly and pH physiological environment (pH 7.4). The presence of HSA-F in both hard and soft scaffolds led to an increase in significant attachment of the scaffolds to the human periodontal ligament fibroblast (PDLF), human umbilical vein endothelial cell (HUVEC), and human osteoblast. Further studies showed that migration (up to 157%), proliferation (up to 400%), and metabolism (up to 210%) of these cells have also improved in the direction of tissue repair. By examining different in vitro and ex ovo experiments, we observed that the final multiphasic scaffold can increase blood vessel density in the process of per-vascularization as well as angiogenesis. By providing a coculture environment including PDLF and HUVEC, important cross-talk between these two cells prevails in the presence of roxadustat drug, a proangiogenic in this study. In vitro and ex ovo results demonstrated significant enhancements in the angiogenic response and cell attachment, indicating the effectiveness of the proposed design. This approach holds promise for the regeneration of complex tissue defects by providing a conducive environment for vascularization and cellular integration, thus promoting tissue healing.

Roxadustat, recently approved, is a hypoxia-inducible factor prolyl hydroxylase inhibitor that has demonstrated favorable safety and efficacy in the treatment of renal anemia. This article reviews main features and possible effects by activation of pathway sequences HREs.

UNASSIGNED: Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, can stimulate erythropoiesis. Our objective was to evaluate the efficacy and safety of roxadustat for the treatment of posttransplantation anemia (PTA).
UNASSIGNED: A total of 150 adult renal transplant recipients who underwent PTA were randomized to either the experimental group or the control group. During the 12-week randomized phase, the experimental group was randomized to oral iron and roxadustat treatment, and the control group was randomized to oral iron treatment only. The randomized phase was followed by a 12-week extended treatment period in which all participants were prescribed roxadustat treatment according to hemoglobin (Hb) levels. All the participants were followed-up with every 4 weeks. The primary end points were the change in Hb levels and response rate throughout the randomized period.
UNASSIGNED: A total of 128 participants completed the randomized treatment period (90 in the experimental group and 38 in the control group). The mean Hb concentration at week 12 was 12.20 g/dl in the experimental group and 11.19 g/dl in the control group. A significantly higher proportion of participants who achieved Hb responses were in the experimental group than in the control group. Differences in serum iron, total iron-binding capacity (TIBC) and transferrin from baseline to week 8 to 12 were significant between the 2 groups. The adverse event profiles were comparable between the 2 groups.
UNASSIGNED: Roxadustat increased Hb in adult renal transplant recipients who underwent PTA, with an adverse event profile comparable to that of the control group.

BACKGROUND: Based on several case reports and observational studies, there is a growing concern regarding the potential association between roxadustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor, and suppression of thyroid function. In this systematic review and meta-analysis (PROSPERO: CRD42023471516), we aimed to evaluate the relationship between roxadustat use and suppression of thyroid function.
METHODS: We conducted a comprehensive search of MEDLINE via PubMed, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials databases using the search term \"roxadustat\" to identify all relevant studies. The study population comprised adults with renal anemia who participated in a randomized controlled trial or observational study, with roxadustat as the intervention and a placebo or erythropoiesis-stimulating agent (ESA) as the comparator. The primary outcome was suppression of thyroid function and the secondary outcome was hypothyroidism. A meta-analysis was conducted using the DerSimonian-Laird random effects model based on the size of the intention-to-treat population, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. Two reviewers independently screened the articles, extracted data, and assessed studies using the ROBINS-I tool.
RESULTS: Of the six studies eligible for inclusion, a meta-analysis was performed using data from two observational studies comparing roxadustat and ESA. The meta-analysis showed that the incidence of suppression of thyroid function was significantly higher with roxadustat use than with ESA use (OR: 6.45; 95% CI: 3.39-12.27; I2 = 12%). Compared with ESA, roxadustat seemed to potentially increase the risk for suppression of thyroid function in patients with renal anemia.
CONCLUSIONS: Our findings highlighted the importance of monitoring thyroid function in patients treated with roxadustat. The results of this review may enhance the safety of using roxadustat to treat renal anemia through advance recognition of the risk for suppression of thyroid function.