Abstract:
:Chronic kidney disease is characterized as impaired renal function along with the imbalance and dysregulation of mineral metabolism; recognized as chronic kidney disease-mineral and bone disorder. Hyperphosphatemia, characterized by altered phosphate homeostasis along with elevated fibroblast growth factor-23 and intact parathyroid hormone, is such an alteration of mineral metabolism. We discovered a novel inhibitor, EOS789, that interacts with several sodium-dependent phosphate transporters (NaPi-IIb, PiT-1, and PiT-2) known to contribute to intestinal phosphate absorption. This inhibitor dose-dependently increased the fecal phosphorus excretion rate and inversely decreased the urinary phosphorus excretion rate in normal rats, suggesting inhibition of intestinal phosphorus absorption. In rats with adenine-induced hyperphosphatemia, EOS789 markedly decreased the serum phosphate, fibroblast growth factor-23, and intact parathyroid hormone below values found in normal control rats. Notably, this pan-phosphate transporter inhibitor exhibited a more potent effect on serum phosphate than a NaPi-IIb-selective inhibitor in rats with hyperphosphatemia indicating that PiT-1 and PiT-2 play important roles in intestinal phosphate absorption. Moreover, in a long-term study, EOS789 sustained the suppression of serum phosphorus in parallel with fibroblast growth factor-23 and intact parathyroid hormone and ameliorated ectopic calcification of the thoracic aorta. Additionally, EOS789 treatment also ameliorated kidney deterioration in rats with progressive kidney injury, probably due to the strict phosphate control. Thus, EOS789 has potent efficacy against hyperphosphatemia and its complications and could provide a significant benefit to patients who are ineffectively treated with phosphate binders.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Tsuboi Y,Ohtomo S,Ichida Y,Hagita H,Ozawa K,Iida M,Nagao S,Ikegami H,Takahashi T,Horiba Ndoi
10.1016/j.kint.2020.02.040subject
Has Abstractpub_date
2020-08-01 00:00:00pages
343-354issue
2eissn
0085-2538issn
1523-1755pii
S0085-2538(20)30406-3journal_volume
98pub_type
杂志文章abstract::Mineral metabolism in chronic kidney disease is attracting intense interest and unprecedented levels of research. The pharmaceutical industry has responded by developing various new agents. Bervoets et al. report the use of an unusual combination of basic-science techniques to increase understanding of the kinetics of...
journal_title:Kidney international
pub_type: 评论,杂志文章,评审
doi:10.1038/ki.2008.627
更新日期:2009-02-01 00:00:00
abstract::Observational studies are valuable and provocative. We are learning about how we practice peritoneal dialysis (PD) and how we might improve on that practice. For example, outcomes of PD therapy are not worse in large patients. Perhaps this will encourage physicians and patients to utilize PD in large patients. In addi...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2009.65
更新日期:2009-07-01 00:00:00
abstract::Clinical trials and experimental studies have highlighted the importance of epigenetic processes in the development of diabetic complications. One of the earliest features of diabetic nephropathy is renal enlargement. The epidermal growth factor (EGF) has a pivotal role in the development of diabetic nephromegaly and ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.39
更新日期:2011-06-01 00:00:00
abstract::Mechanisms responsible for renal hemodynamic alterations were studied in jaundiced (by bile-duct ligation) rabbits (BDL) 10 days after ligation of the biliary tract, in comparison with sham-operated rabbits (SO). Arterial hematocrit, plasma volume, blood pressure, abdominal inferior vena cava pressure, and heart rate ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.25
更新日期:1980-02-01 00:00:00
abstract::The cross talk between the immune and nervous systems is critical not only for maintaining normal homeostasis but also for the progression of a variety of inflammatory diseases. Macrophage activation and β2-adrenergic receptors are known to play important roles in facilitating this communication between these 2 system...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2017.03.024
更新日期:2017-07-01 00:00:00
abstract::Progressive kidney fibrosis precedes end-stage renal failure in up to a third of patients with diabetes mellitus. Elevated intra-renal transforming growth factor-beta (TGF-beta) is thought to underlie disease progression by promoting deposition of extracellular matrix and epithelial-mesenchymal transition. GW788388 is...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002717
更新日期:2008-03-01 00:00:00
abstract:BACKGROUND:Low birth weight is an important risk factor for hypertension and unfavorable prognoses of a number of renal diseases. It is also associated with reduced kidney size and nephron number. A differentiation between the effects of low birth weight versus being born premature or small for gestational age has, how...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00451.x
更新日期:2005-08-01 00:00:00
abstract::Hyper-activation of Rac1, a small GTPase, in glomerular podocytes has been implicated in the pathogenesis of familial proteinuric kidney diseases. However, the role of Rac1 in acquired nephrotic syndrome is unknown. To gain direct insights into this, we generated a transgenic mouse model expressing a doxycycline-induc...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.03.010
更新日期:2017-08-01 00:00:00
abstract::Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such 'double-positive' cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients ...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2017.03.014
更新日期:2017-09-01 00:00:00
abstract:BACKGROUND:Candidate biomarkers for vasculopathy in systemic lupus erythematosus (SLE) include circulating endothelial cells and the recently identified endothelial protein C receptor (EPCR) which, when shed, promotes a thrombotic diathesis. This study sought correlation between plasma levels of soluble EPCR and diseas...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00385.x
更新日期:2005-07-01 00:00:00
abstract::Adiponectin levels are increased in patients with type I diabetes especially in the presence of microangiopathy. Here we determined the predictive value of serum adiponectin levels and 8 adiponectin gene polymorphisms for mortality, cardiovascular events and end-stage renal disease in type I diabetic patients. This pr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.201
更新日期:2008-09-01 00:00:00
abstract::The adjuvanted hepatitis B vaccine, HB-AS04, elicits more rapid and persistent protective antibody concentrations than double doses of conventional recombinant vaccines in patients with renal insufficiency. We compared the immunogenicity, reactogenicity, and safety of the AS02(V)-adjuvanted hepatitis B vaccine HB-AS02...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/ki.2009.454
更新日期:2010-02-01 00:00:00
abstract::Heterozygous mutations of the tissue-specific transcription factor hepatocyte nuclear factor (HNF)1beta, cause maturity onset diabetes of the young (MODY5) and kidney anomalies including agenesis, hypoplasia, dysplasia and cysts. Because of these renal anomalies, HNF1beta is classified as a CAKUT (congenital anomalies...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.149
更新日期:2008-07-01 00:00:00
abstract::Conventional peritoneal dialysis (PD) fluids are known to inhibit polymorphonuclear cells (PMN) phagocytosis, oxidative burst and enzyme release. However, the relative contributions of apoptosis and/or necrosis to this dysfunction have not been examined. We investigated the effects of osmolality, glucose concentration...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.495
更新日期:1997-12-01 00:00:00
abstract::Stimulation of proximal tubule cell (PTC) growth in a variety of physiological and pathological renal conditions is preceded by increased renal production of transforming growth factor-beta 1 (TGF-beta 1) and by augmented tubular sodium transport via activated sodium hydrogen exchange (NHE). Since TGF-beta 1 has been ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00916.x
更新日期:1998-06-01 00:00:00
abstract:BACKGROUND:Assessment of mRNA levels has the potential to predict renal outcome. The objective of this study was to optimize several steps in the protocol for obtaining cDNA from routine clinical kidney biopsy material. METHODS:RNA integrity was compared between different methods for extraction of RNA, synthesis of cD...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00366.x
更新日期:2004-01-01 00:00:00
abstract::The effects of chronic respiratory alkalosis on divalent ion homeostasis have not been reported in any species. We studied four normal male subjects during a four-day control period (residence at 500 m), during six days of chronic respiratory alkalosis induced by hypobaric hypoxia (residence at 3450 m), followed by a ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.340
更新日期:1992-09-01 00:00:00
abstract:BACKGROUND:In inflammation, urokinase plasminogen activator (uPA) and its receptor (uPAR) play an important role in fibrinolysis and in activation and chemotaxis of neutrophils and lymphocytes. Moreover, the uPA/uPAR system is involved in processes that affect turnover of the extracellular matrix (ECM). The aim of this...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00261.x
更新日期:2003-11-01 00:00:00
abstract::The transition between the glomerulus and the proximal tubule was studied by light and electron microscopy in perfusion-fixed rabbit kidneys. In most nephrons a transitional segment of tubule occurred between the Bowman's capsule and the proximal tubule proper. This initial part of the tubule was lined by flattened ce...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1975.22
更新日期:1975-03-01 00:00:00
abstract:BACKGROUND:The alteration of renal cell growth is one of the early abnormalities in the diabetic nephropathy. However, the effects of high glucose and its action mechanism in renal proximal tubule cell (PTC) proliferation have not been elucidated. METHODS:The effects of 25 mmol/L glucose on cell proliferation, thymidi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0590051695.x
更新日期:2001-05-01 00:00:00
abstract:BACKGROUND:Small, uncontrolled studies of dialysis-dependent chronic kidney disease (CKD) patients have demonstrated abnormalities of cardiovascular autonomic control and vascular compliance, which may contribute to adverse cardiovascular morbidity in this population. However, there is little information utilizing newe...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00165.x
更新日期:2005-03-01 00:00:00
abstract::Cell-cycle proteins influence almost all aspects of embryogenesis and differentiation. In adults, these proteins control cell division and regeneration after injury. During the past several years, their roles in controlling reaction to stress have been demonstrated in several organ systems. In the kidney, the cell typ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2009.562
更新日期:2010-04-01 00:00:00
abstract::Long-term outcomes of kidney allografts have shown only marginal improvement over the last three decades, despite the remarkable improvement in acute rejection and one-year graft survival. Novel biomarkers of tubular injury may prevent irreversible damage to the tubulointerstitial compartment and improve allograft sur...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002772
更新日期:2008-03-01 00:00:00
abstract::Our findings indicate that hypoaldosteronism occurs commonly (23/31 patients) in hyperkalemic patients with chronic renal insufficiency and that the deficiency of aldosterone contributes to the pathogenesis of the hyperkalemia. In most patients (83%), hypoaldosteronism could be accounted for by deficient renal secreti...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.11
更新日期:1980-01-01 00:00:00
abstract::Swelling activated anion channels have recently been recognized to play an important role in not only volume regulatory electrolyte movement, but also in organic osmolyte transport. A swelling-activated, outwardly rectifying anion channel termed VSOAC (volume-sensitive organic osmolyte/anion channel) is a major pathwa...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1996.250
更新日期:1996-06-01 00:00:00
abstract::Coronary artery stenosis induces renal inflammation and kidney injury in pigs even in the absence of myocardial infarction or clinically significant heart failure. This effect is aggravated by experimentally induced renovascular hypertension. Interestingly, oxidative stress originating from the ischemic myocardium was...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2014.431
更新日期:2015-04-01 00:00:00
abstract::Spleen tyrosine kinase (SYK) is an important component of the intracellular signaling pathway for various immunoreceptors. Inhibition of SYK has shown promise in preclinical models of autoimmune and glomerular disease. However, the description of SYK expression in human renal tissue, which would be desirable ahead of ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.29
更新日期:2015-07-01 00:00:00
abstract::The hypoxia-inducible factor-1 (HIF-1) was first described as a DNA binding activity that specifically recognizes an 8 bp hypoxia response element (HRE) known to be essential for oxygen-regulated erythropoietin gene expression. In electrophoretic mobility shift assays (EMSAs) HIF-1 DNA binding activity is only detecta...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.80
更新日期:1997-02-01 00:00:00
abstract:BACKGROUND:Unilateral ureteral obstruction (UUO) leads to interstitial fibrosis of the obstructed kidney, and TGF-beta is considered to play an important role in this fibrotic process. Smad7 has been recently identified as an antagonist of TGF-beta signaling. To investigate whether this novel molecule can be exploited ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.0610s1094.x
更新日期:2002-01-01 00:00:00
abstract::Clinical and experimental studies have shown that serum aluminum (Al) is bound to transferrin and that cellular uptake of Al appears to be mediated by transferrin receptors. Based on these findings it is widely believed that intestinal Al absorption occurs via iron-specific, transferrin-dependent pathways and that iro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.509
更新日期:1996-12-01 00:00:00