Abstract：
:The treatment of hyperphosphatemia remains challenging in patients receiving hemodialysis. This Phase 1b study assessed safety and efficacy of EOS789, a novel pan-inhibitor of phosphate transport (NaPi-2b, PiT-1, PiT-2) on intestinal phosphate absorption in patients receiving intermittent hemodialysis therapy. Two cross-over, randomized order studies of identical design (ten patients each) compared daily EOS789 50 mg to placebo with meals and daily EOS789 100 mg vs EOS789 100 mg plus 1600 mg sevelamer with meals. Patients ate a controlled diet of 900 mg phosphate daily for two weeks and began EOS789 on day four. On day ten, a phosphate absorption testing protocol was performed during the intradialytic period. Intestinal fractional phosphate absorption was determined by kinetic modeling of serum data following oral and intravenous doses of 33Phosphate (33P). The results demonstrated no study drug related serious adverse events. Fractional phosphate absorption was 0.53 (95% confidence interval: 0.39,0.67) for placebo vs. 0.49 (0.35,0.63) for 50 mg EOS789; and 0.40 (0.29,0.50) for 100 mg EOS789 vs. 0.36 (0.26,0.47) for 100 mg EOS789 plus 1600 mg sevelamer (all not significantly different). The fractional phosphate absorption trended lower in six patients who completed both studies with EOS789 100 mg compared with placebo. Thus, in this Phase 1b study, EOS789 was safe and well tolerated. Importantly, the use of 33P as a sensitive and direct measure of intestinal phosphate absorption allows specific testing of drug efficacy. The effectiveness of EOS789 needs to be evaluated in future Phase 2 and Phase 3 studies.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Hill Gallant KM,Stremke ER,Trevino L,Moorthi RN,Doshi S,Wastney ME,Hisada N,Sato J,Ogita Y,Fujii N,Matsuda Y,Kake T,Moe SMdoi
10.1016/j.kint.2020.09.035subject
Has Abstractpub_date
2020-10-30 00:00:00eissn
0085-2538issn
1523-1755pii
S0085-2538(20)31246-1pub_type
杂志文章abstract：:Progranulin (PGRN), an autocrine growth factor, has multiple physiological functions and is widely involved in the pathogenesis of many types of diseases. The pivotal anti-inflammatory function of PGRN in rheumatoid arthritis encouraged us to examine the role of PGRN in acute kidney injury (AKI). We found that levels ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2014.403
更新日期：2015-05-01 00:00:00
abstract：:Transcriptome analysis of a rat polycystic kidney disease (PKD) model: importance of genes involved in extracellular matrix metabolism. PKD is a common genetic cause of chronic renal failure, and is characterized by the accumulation of fluid-filled cysts in the kidneys and other organs. Abnormalities in the expression...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/sj.ki.5000309
更新日期：2006-05-01 00:00:00
abstract：BACKGROUND:The parathyroid (PT) hyperplasia induced by renal failure can be further enhanced by high dietary phosphate (P) or completely abolished by P restriction. To identify potential mechanisms mediating these opposing effects of dietary P on PT growth, this study first focused on p21(WAF1) (p21) because high P red...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2001.059003855.x
更新日期：2001-03-01 00:00:00
abstract：:Using a combination of intra-operative digital photography and micro-biopsy we measured renal cortical and papillary changes in five patients with primary hyperparathyroidism and abundant calcium phosphate kidney stones. Major tissue changes were variable papillary flattening and retraction, dilation of the ducts of B...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2008.161
更新日期：2008-07-01 00:00:00
abstract：:Adenosine is known to decrease renal blood flow and glomerular filtration rate. We have tested the hypothesis that adenosine exerts contractile effects on mesangial cells. Furthermore, we have studied, using selective agonists and antagonists for adenosine, which kind of adenosine receptor, A1 or A2, is mainly implica...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1989.126
更新日期：1989-06-01 00:00:00
abstract：:The impact of dialysis on cognitive trends is uncertain. Kurella Tamura et al. evaluated cognitive trajectories in 212 participants from the Chronic Renal Insufficiency Cohort study and found that dialysis initiation was associated with a decline in executive function. This is consistent with a cerebrovascular basis f...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1016/j.kint.2017.01.022
更新日期：2017-04-01 00:00:00
abstract：:Modern dietary habits are characterized by high-sodium and low-potassium intakes, each of which was correlated with a higher risk for hypertension. In this study, we examined whether long-term variations in the intake of sodium and potassium induce lasting changes in the plasma concentration of circulating steroids by...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2011.15
更新日期：2011-08-01 00:00:00
abstract：:Low-protein diets (LPD) increase insulin-mediated glucose disposal in chronic renal failure (CRF), but the fate of the better utilized glucose and the effect on energy production rate are unknown. Using a two-step (1 and 5 mU x kg(-1) x min(-1)) euglycemic hyperinsulinemic clamp combined with indirect calorimetry, we ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1997.167
更新日期：1997-04-01 00:00:00
abstract：:The parathyroid hormone (PTH) response to hypocalcemia was studied in 18 hemodialysis patients with osteitis fibrosa, and the relationship with PTH and bone histology in 26 hemodialysis patients. Hypocalcemia was produced during hemodialysis by the use of a dialysate devoid of calcium. Both amino (N) (P less than 0.05...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1984.37
更新日期：1984-02-01 00:00:00
abstract：:We have studied the effect of neutralizing the surface charge of rat glomerular epithelial cells (GEC) in culture on prostanoid production. Incubation of rat GEC with polycations poly-L-lysine (PL) resulted in a dose dependent increase of 6-keto-PGF1 alpha (up to 8 to 10-fold) and PGE2 (up to 7 to 8-fold) production. ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1987.171
更新日期：1987-07-01 00:00:00
abstract：:Besides its procoagulant activity, thrombin has been shown to stimulate cell proliferation and to regulate the fibrinolytic pathway. We report here the effect of purified human alpha thrombin on the synthesis of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) by cultured human me...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1990.297
更新日期：1990-11-01 00:00:00
abstract：BACKGROUND:Nitric oxide (NO) has been shown to be a paracrine/autocrine regulator of proximal tubular transport. In this study, we investigated the effect of NO on the paracellular permeability of opossum kidney (OK) cells, a proximal tubule cell line that possesses a leaky paracellular pathway resembling that of the i...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.1999.00465.x
更新日期：1999-06-01 00:00:00
abstract：:An open, randomized trial study on the therapeutic effect of recombinant alpha-interferon (IFN alpha) in 40 patients with hepatitis B virus membranous nephropathy (HBVMN) was conducted. All were pathologically proven to have HBVMN which showed no response to corticosteroid treatment represented by persistent heavy pro...
journal_title：Kidney international
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1038/ki.1995.27
更新日期：1995-01-01 00:00:00
abstract：:Kidney fibrosis is one of the most promising treatment targets in nephrology. To design effective treatment approaches, a detailed understanding of the initiating mechanisms is of great importance. Kim and Pandanilam now find that renal nerves are a major trigger for renal fibrosis. Both afferent and efferent nerve fi...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1038/ki.2014.327
更新日期：2015-02-01 00:00:00
abstract：:Hemodynamic studies were performed at two levels of dietary sodium intake (10 mmoles/day and 100 mmoles/day for 14 days) in a group of patients (with retained kidneys) on chronic hemodialysis. Plasma renin activity and aldosterone, plasma, and extracellular fluid (ECF) volumes were measured while the patient were at r...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1977.114
更新日期：1977-10-01 00:00:00
abstract：:Despite the increasing knowledge of the role of gangliosides in normal and diseased tissues, little is known of the presence, distribution and functions of these molecules in the kidney. In this study we analyzed the main gangliosides of isolated glomeruli and cortical, medullary and papillary fractions of the human, ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1994.14
更新日期：1994-01-01 00:00:00
abstract：:The epidemic of chronic kidney disease in Nicaragua (Mesoamerican nephropathy) has been linked with recurrent dehydration. Here we tested whether recurrent dehydration may cause renal injury by activation of the polyol pathway, resulting in the generation of endogenous fructose in the kidney that might subsequently in...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2013.492
更新日期：2014-08-01 00:00:00
abstract：:Carefully age-matched, purebred male beagle dogs that underwent uninephrectomy one month after they were made diabetic with alloxan were used to establish a model of rapidly developing diabetic nephropathy in a large animal. The diabetic animals, all requiring insulin, were divided into two groups: one group with cont...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1982.88
更新日期：1982-05-01 00:00:00
abstract：:During vasculitis, activation of the kinin system induces inflammation, whereby the kinin B1-receptor is expressed and activated after ligand binding. Additionally, activated blood cells release microvesicles into the circulation. Here we determined whether leukocyte-derived microvesicles bear B1-kinin receptors durin...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2016.09.023
更新日期：2017-01-01 00:00:00
abstract：:Experiments in rodents have demonstrated an important role for selectins in kidney ischemia-reperfusion injury (IRI). However, the relevance of this in larger mammals, as well as the impact on long-term structure and function is unknown. We tested the hypothesis that small molecule selectin ligand inhibition attenuate...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/sj.ki.5000335
更新日期：2006-05-01 00:00:00
abstract：:A protective role for sirtuin 6 (Sirt6) in the context of chronic renal injury is reported by Cai et al. in this issue of Kidney International. The mechanism is thought to be mediated by Sirt6's deacetylase activity, specifically on β-catenin target genes. This commentary discusses these results and the interaction be...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1016/j.kint.2019.09.022
更新日期：2020-01-01 00:00:00
abstract：:Chronic balance studies were performed in six adrenalectomized patients to investigate the renal and systemic acid-base consequences of mineralocorticoid deficiency in the absence of either glucocorticoid deficiency or parenchymal renal disease. Constant glucocorticoid replacement was provided with dexamethasone, 750 ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1980.195
更新日期：1980-12-01 00:00:00
abstract：:Tubular atrophy and interstitial fibrosis, important in progression of renal diseases, including diabetic (D) and cyclosporine-induced (CSA) nephropathy, have been considered irreversible. Normoglycemia for 10 years following pancreas transplantation alone (PTA) reversed D glomerulopathy lesions. This study quantified...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/sj.ki.5000153
更新日期：2006-03-01 00:00:00
abstract：:Recent advances have led to a greater appreciation of how mitochondrial dysfunction contributes to diverse acute and chronic pathologies. Indeed, mitochondria have received increasing attention as a therapeutic target in a variety of diseases because they serve as key regulatory hubs uniquely situated at crossroads be...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1016/j.kint.2017.05.034
更新日期：2017-11-01 00:00:00
abstract：:IgA nephropathy is the most common primary glomerulonephritis worldwide. Its frequent coexistence with inflammatory, infectious, or malignant processes raises the possibility of a pathologic rather than coincidental association. Major strides have been made to elucidate the underlying pathophysiologic events that culm...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1016/j.kint.2018.02.030
更新日期：2018-10-01 00:00:00
abstract：BACKGROUND:High blood glucose levels play major roles in the pathogenesis of renal diabetic complications through non-enzymatic glycation. For long-lived molecules this leads to formation of advanced glycation end products (AGE), and the renal extracellular matrix appears to be one of the targets for such processes. Us...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.1998.00030.x
更新日期：1998-08-01 00:00:00
abstract：BACKGROUND:The relationship between blood pressure (BP) and mortality in hemodialysis patients has remained controversial. Some studies suggested that a lower pre- or postdialysis BP was associated with excess mortality, while others showed poorer outcome in patients with uncontrolled hypertension. We conducted a multi...
journal_title：Kidney international
pub_type： 杂志文章,多中心研究
doi：10.1111/j.1523-1755.2004.00812.x
更新日期：2004-09-01 00:00:00
abstract：:Hypoxia in the embryo is a frequent cause of intra-uterine growth retardation, low birth weight, and multiple organ defects. In the kidney, this can lead to low nephron endowment, predisposing to chronic kidney disease and arterial hypertension. A key component in cellular adaptation to hypoxia is the hypoxia-inducibl...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2017.06.015
更新日期：2017-12-01 00:00:00
abstract：:To determine whether acute renal failure (ARF) increases the long-term risk of progressive chronic kidney disease (CKD), we studied the outcome of patients whose initial kidney function was normal or near normal but who had an episode of dialysis-requiring ARF and did not develop end-stage renal disease within 30 days...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2009.289
更新日期：2009-10-01 00:00:00
abstract：:Chronic inflammation is a complication of conventional hemodialysis that induces progressive cardiovascular damage. An apparently straightforward manipulation to treat this-removal of a large amount of uremic toxins by convection-has proven that the relationships between inflammation and convective techniques such as ...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1038/ki.2014.81
更新日期：2014-08-01 00:00:00
