Molecules, Vol. 23, Pages 1123: Transcription Factors as Therapeutic Targets in Chronic Kidney Disease

Molecules, Vol. 23, Pages 1123: Transcription Factors as Therapeutic Targets in Chronic Kidney Disease Molecules doi: 10.3390/molecules23051123 Authors: Akihito Hishikawa Kaori Hayashi Hiroshi Itoh The growing number of patients with chronic kidney disease (CKD) is recognized as an emerging problem worldwide. Recent studies have indicated that deregulation of transcription factors is associated with the onset or progression of kidney disease. Several clinical trials indicated that regression of CKD may be feasible via activation of the transcription factor nuclear factor erythroid-2 related factor 2 (Nrf2), which suggests that transcription factors may be potential drug targets for CKD. Agents stabilizing hypoxia-inducible factor (HIF), which may be beneficial for renal anemia and renal protection, are also now under clinical trial. Recently, we have reported that the transcription factor Kruppel-like factor 4 (KLF4) regulates the glomerular podocyte epigenome, and that the antiproteinuric effect of the renin–angiotensin system blockade may be partially mediated by KLF4. KLF4 is one of the Yamanaka factors that induces iPS cells and is reported to be involved in epigenetic remodeling. In this article, we summarize the transcription factors associated with CKD and particularly focus on the possibility of transcription factors being novel drug targets for CKD through epigenetic modulation.
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research

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Publication date: October 2018Source: American Journal of Kidney Diseases, Volume 72, Issue 4Author(s): Yoshio N. HallThere is ongoing recognition that a wide array of social, economic, and environmental factors influence individuals’ opportunities to engage in health care and healthy behaviors. Despite spending $34 billion annually on the care of patients with end-stage renal disease, the American public and nephrology community remain remarkably complacent about addressing “upstream” factors that influence the prevention, progression, and treatment of chronic kidney diseases. Recently, a growing number ...
Source: American Journal of Kidney Diseases - Category: Urology & Nephrology Source Type: research
AbstractBackgroundIron deficiency is a common cause of anemia in pediatric patients with hemodialysis-dependent chronic kidney disease (CKD-5HD). Ferric pyrophosphate citrate (FPC, Triferic ®) donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Administration of FPC via dialysate or intravenously (IV) may provide a suitable therapeutic option to current IV iron preparations for these patients.MethodsThe pharmacokinetics and safety of FPC administered via dialysate and IV to patients aged
Source: Pediatric Nephrology - Category: Urology & Nephrology Source Type: research
AbstractBackground25-Hydroxyvitamin D (25OHD) deficiency is common in children with chronic kidney disease (CKD). It has been associated with an increased risk for anemia in both healthy US children and in adults with CKD. This association has not been explored in children with CKD.MethodsChildren aged 1 –16 enrolled in the Chronic Kidney Disease in Children (CKiD) study with mild to moderate kidney dysfunction, and with 25OHD measured at baseline (n = 580), were included in the analysis. The cross-sectional associations between 25OHD and hemoglobin (g/dL) and anemia were assessed. Anemia was defined as hemoglobin
Source: Pediatric Nephrology - Category: Urology & Nephrology Source Type: research
ConclusionsOur findings support the presence of erythropoiesis inhibitory substances in uremic sera. EPO/EPO-R-dependent mechanisms may play a role in inhibiting erythropoiesis. The in vitro bioassay described herein may serve as an indicator of rHuEPO responsiveness which may encourage further investigation of underlying mechanisms of EPO resistance.
Source: Pediatric Nephrology - Category: Urology & Nephrology Source Type: research
An overview of the treatments for anaemia in chronic kidney disease and the tests needed to prescribe and assess their effectiveness.
Source: Clinical Pharmacist - Category: Drugs & Pharmacology Source Type: research
Z, Tesař V, Vokurka M Abstract Hepcidin is a key regulator of iron metabolism and plays an important role in many pathologies. It is increased by iron administration and by inflammation, while erythropoiesis downregulates its expression. It decreases iron availability and thus contributes to anemia of chronic diseases. The aim of the study was to measure hepcidin as a marker and pathogenic factor in ANCA-associated vasculitis (AAV). Hepcidin plasma concentration was measured by the immunological method in 59 patients with AAV and compared to patients with non-vasculitic etiology of chronic kidney disease, patien...
Source: Physiological Research - Category: Physiology Authors: Tags: Physiol Res Source Type: research
In this study, we further investigated the effects of other protein-bound uremic toxins on HIF-dependent EPO expression using EPO-producing HepG2 cells. We found that indoxyl glucuronide (IG) and IS, but not p-cresyl sulfate, phenyl sulfate, 3-indoleacetic acid or hippuric acid, inhibited hypoxia mimetic cobalt chloride-induced EPO mRNA expression. Furthermore, IG at concentrations similar to the blood levels in CKD patients inhibited the transcriptional activation of HIF induced by both cobalt chloride treatment and hypoxic culture. IG also induced CYP1A1 mRNA expression and nuclear translocation of AHR protein, indicatin...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
Conclusions: Switching to RetacritTM was non-inferior to continuing ­Epogen® in maintaining hemoglobin levels in patients receiving hemodialysis, when both ESAs were dosed using a specified algorithm (ClinicalTrials.gov, NCT02504294).Am J Nephrol 2018;48:214 –224
Source: American Journal of Nephrology - Category: Neurology Source Type: research
Conclusions: TP0463518 induced dose-dependent EPO production, mainly derived from the liver in HV and CKD patients. These results suggest that TP0463518 is a new strategy for treating anemia in CKD, which can be used regardless of renal functions.Am J Nephrol 2018;48:157 –164
Source: American Journal of Nephrology - Category: Neurology Source Type: research
Authors: Auerbach M, Chertow GM, Rosner M Abstract INTRODUCTION: Ferumoxytol is a superparamagnetic molecule originally developed as a contrast agent for magnetic resonance imaging. Elemental iron is contained within the carbohydrate core and is released slowly after infusion allowing a large dose of iron to be administered in a short period of time. Ferumoxytol, originally approved for iron deficiency in chronic kidney disease, received a broad label for any cause of iron deficiency after oral iron intolerance or in those circumstances when oral iron is ineffective or harmful. AREAS COVERED: The chemistry, pha...
Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research
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