Abstract：
:Patients with chronic kidney disease have elevated circulating asymmetric dimethylarginine (ADMA). Recent studies have suggested that ADMA impairs endothelial nitric oxide synthase (eNOS) by effects other than competition with the substrate L-arginine. Here, we sought to identify the molecular mechanism by which increased ADMA causes endothelial dysfunction in a chronic kidney disease model. In wild-type mice with remnant kidney disease, blood urea nitrogen, serum creatinine, and ADMA were increased by 2.5-, 2-, and 1.2-fold, respectively, without any change in blood pressure. Nephrectomy reduced endothelium-dependent relaxation and eNOS phosphorylation at Ser1177 in isolated aortic rings. In transgenic mice overexpressing dimethylarginine dimethylaminohydrolase-1, the enzyme that metabolizes ADMA, circulating ADMA was not increased by nephrectomy and was decreased to half that of wild-type mice. These mice did not exhibit the nephrectomy-induced inhibition of both endothelium-dependent relaxation and eNOS phosphorylation. In cultured human endothelial cells, agonist-induced eNOS phosphorylation and nitric oxide production were decreased by ADMA at concentrations less than that of L-arginine in the media. Thus, elevated circulating ADMA may be a cause, not an epiphenomenon, of endothelial dysfunction in chronic kidney disease. This effect may be attributable to inhibition of eNOS phosphorylation.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Kajimoto H,Kai H,Aoki H,Yasuoka S,Anegawa T,Aoki Y,Ueda S,Okuda S,Imaizumi Tdoi
10.1038/ki.2011.476subject
Has Abstractpub_date
2012-04-01 00:00:00pages
762-8issue
8eissn
0085-2538issn
1523-1755pii
S0085-2538(15)55386-6journal_volume
81pub_type
杂志文章abstract：:Scavenger receptor A (SR-A) is a key transmembrane receptor in the endocytosis of lipids and contributes to the pathogenesis of atherosclerosis. To assess its role in hyperlipidemic chronic kidney disease, wild-type and SR-A-deficient (knockout) mice underwent uninephrectomy followed by either normal or high-fat diet....
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2011.457
更新日期：2012-05-01 00:00:00
abstract：BACKGROUND:Inhibition of the renin-angiotensin system (RAS) prevents development of chronic allograft dysfunction in experimental animals. Whether this therapeutic approach is effective even if started when signs of allograft nephropathy are already manifested has not been investigated. METHODS:To address this issue, ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2003.00318.x
更新日期：2003-12-01 00:00:00
abstract：BACKGROUND:It is still unclear whether age per se is associated with preservation of renal functional reserve, that is, of the increase in glomerular filtration rate (GFR) induced by appropriate vasodilating stimulus. METHODS:To gain insights into this issue, we evaluated the renal response to a maximal vasodilating s...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2001.0590031052.x
更新日期：2001-03-01 00:00:00
abstract：:X-linked Alport syndrome (AS) associated with diffuse esophageal leiomyomatosis (DL) has been reported to be due to deletions removing the 5' ends of both the COL4A5 and COL4A6 genes, encoding the alpha 5 and alpha 6 chains of type IV collagen, respectively, whereas a variety of mutations in COL4A5 has been identified...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1995.489
更新日期：1995-12-01 00:00:00
abstract：:Previous studies in living animals have suggested that variations in the serum concentrations of calcium and phosphate directly affect renal tubular bicarbonate transport. To examine this area more directly, we measured the bicarbonate and the fluid transport in isolated rabbit proximal convoluted and straight tubules...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1982.43
更新日期：1982-03-01 00:00:00
abstract：:Quartan malarial infection causes an immune complex nephritis in some individuals, which, once established, is sustained by mechanisms not yet fully explained, but which probably involve autoimmune processes. The presenting clinical and biochemical findings of the quartan malarial nephrotic syndrome are similar to tho...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1979.103
更新日期：1979-07-01 00:00:00
abstract：:To examine whether hypoxia-inducible factor (HIF)-1α mediates the profibrotic effects of angiotensin II, we treated cultured renal medullary interstitial cells with angiotensin II and found that it increased HIF-1α levels. This was accompanied by a significant upregulation of collagen I/III, the tissue inhibitor of me...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2010.326
更新日期：2011-02-01 00:00:00
abstract：:Nephropathia epidemica (NE) caused by Puumala hantavirus is one type of hemorrhagic fever with renal syndrome (HFRS). There is considerable variability in the clinical severity of NE. Many infections are subclinical but the disease can even be fatal. We questioned whether the wide spectrum in the outcome of NE is depe...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1996.29
更新日期：1996-01-01 00:00:00
abstract：:Spontaneous and aspirated blood samples were collected from the welling points of surface efferent arterioles in the rat kidney. The amount of tubular reabsorbate in each sample was calculated from measurements of the inulin concentration in the sample and systemic arterial plasma. Both spontaneous and aspirated sampl...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1984.44
更新日期：1984-03-01 00:00:00
abstract：BACKGROUND:Susceptibility to skin cancer after transplantation is multifactorial, and risk factors include skin type, sun exposure, and level of immunosuppression. A major mechanism of carcinogenesis is ultraviolet radiation-induced free radical damage, and genetically determined ability to metabolize free radicals may...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1111/j.1523-1755.2000.00392.x
更新日期：2000-11-01 00:00:00
abstract：BACKGROUND:Recently, we observed that the severity of glomerulonephritis in an experimental model of immunoglobulin A nephropathy (IgAN) induced by Sendai virus differs between C57BL/6 and BALB/c mouse strains. The determinants of differing renal insufficiency are not understood. In the present study, we examine the ca...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2003.00258.x
更新日期：2003-11-01 00:00:00
abstract：:The kidneys excrete the daily acid load mainly by generating and excreting ammonia but the underlying molecular mechanisms are not fully understood. Here we evaluated the role of the inwardly rectifying potassium channel subunit Kir4.2 (Kcnj15 gene product) in this process. In mice, Kir4.2 was present exclusively at t...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2019.09.028
更新日期：2020-02-01 00:00:00
abstract：:In normal subjects, beta-adrenergic stimulation lowers the serum potassium, whereas alpha-stimulation raises it. Epinephrine, a mixed alpha and beta agonist, acutely lowers the blood potassium in normal subjects, but not in patients with end-stage renal disease. This study was designed to determine whether the resista...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1991.321
更新日期：1991-12-01 00:00:00
abstract：:The relationship between leukopenia and the complement system during hemodialysis was re-examined by studying not only the in vivo effects of four different dialyzer membranes (cellulose hydrate, cuprophan, cellulose acetate, and polyacrilonitrile) on leukocyte counts and complement levels, but especially by investiga...
journal_title：Kidney international
pub_type： 临床试验,杂志文章
doi：10.1038/ki.1983.227
更新日期：1983-12-01 00:00:00
abstract：:Major temporal changes in the case mix of patients accepted for renal replacement therapy impede analysis of long-term mortality trends in end-stage renal disease patients. A record linkage study of 2 large electronic hospital inpatient data sets with national mortality data used standardization by age, sex, and comor...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1016/j.kint.2018.01.002
更新日期：2018-05-01 00:00:00
abstract：:In order to study the effects of acute ureteral obstruction on glomerular hemodynamics, glomerular hydrostatic capillary pressure (PG), pressure in the first-order peritubular capillaries (EAP), and intratubular pressure (PT) were directly measured in superficial nephrons on Munich-Wistar rats by micropuncture with a ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1977.131
更新日期：1977-12-01 00:00:00
abstract：:Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are exposed to a continuous infusion of glucose via their peritoneal cavity. We performed studies to quantitate the amount of energy derived from dialysate glucose. Net glucose absorption averaged 182 +/- (SD) 61 g/day in 19 studies with a dialysate ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1981.53
更新日期：1981-04-01 00:00:00
abstract：:In this issue, McMahon et al. report that, by combining phenotypic, metabolomic, and genetic data, they could better detect chronic kidney disease at the early stages and provide insight into its pathobiology. The most significant findings of the study are that several urinary metabolites (e.g., glycine and histidine)...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1016/j.kint.2017.03.022
更新日期：2017-06-01 00:00:00
abstract：:Bone-derived fibroblast growth factor-23 (FGF23) plays an important role in systemic phosphate turnover. Increased FGF23 activity results in hypophosphatemic disorders, while reduced activity is linked to hyperphosphatemic disorders. FGF23, together with klotho as co-factor, can activate FGF receptors in its target ti...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1038/ki.2014.316
更新日期：2014-12-01 00:00:00
abstract：BACKGROUND:Urea kinetic modeling (UKM) and food records are widely used to assess the dialysis adequacy. Clinicians use these methods in individual patients to decide whether the dialysis prescription should be adjusted. We determined the variation in UKM parameters and dietary intake within individual patients in orde...
journal_title：Kidney international
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1046/j.1523-1755.1999.00412.x
更新日期：1999-05-01 00:00:00
abstract：:Murine double minute (MDM)-2, an E3 ubiquitin ligase, promotes cancer cell survival and growth, by degrading the cell cycle regulator p53. Antagonism of MDM2 by the small-molecule cis-imidazoline nutlin analogs is under current study for cancer therapy. To test whether MDM2 also promotes regenerative cell growth, we d...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2011.482
更新日期：2012-06-01 00:00:00
abstract：BACKGROUND:Fractalkine is a newly identified T-cell and monocyte/macrophage (Mphi) chemokine with a transmembrane domain and is a cell-surface protein on activated endothelium. It can mediate adhesion of cells expressing the fractalkine receptor CX3CR1. These unique features make fractalkine well suited for leukocyte r...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.1999.00604.x
更新日期：1999-08-01 00:00:00
abstract：:Germ free rats provide a unique model in which to assess biological response to environment. In 48 germ-free male, Sprague-Dawley rats we examined the consequences of oral exposure to nordihydroguaiaretic acid (NDGA), a nephrotoxin; to Staphylococcus epidermidis and bacillus species, non-endotoxin-containing bacteria;...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1987.213
更新日期：1987-09-01 00:00:00
abstract：:A morphometric technique is used to estimate the absolute and relative surface areas of the brush border microvilli and cell walls bordering lateral intercellular spaces. In isolated, perfused proximal tubule from rabbit, the luminal and lateral surfaces are equal in area. For proximal convoluted tubules (PCT) each su...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1975.125
更新日期：1975-12-01 00:00:00
abstract：:The presence of CR1 mRNA in podocytes was investigated using a 35S-labeled CR1 cDNA probe and in situ hybridization in sections from fetal and adult human kidneys. CR1 mRNA was only detected in immature podocytes at early stages of glomerular differentiation in the fetal kidney. In contrast, CR1 antigen was abundantly...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1990.198
更新日期：1990-08-01 00:00:00
abstract：:Intravital multiphoton microscopy is a powerful tool to study kidney physiology in living animals. However, certain technical issues have curbed its usage to date, including limited depth of tissue penetration and high background emission of endogenous signals. Most previous studies have used the excitation range 700–...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2015.323
更新日期：2016-03-01 00:00:00
abstract：:Osteopontin (OPN) is a secreted acidic glycoprotein that has potent monocyte chemoattractant and adhesive properties. Up-regulation of tubular OPN expression is thought to promote interstitial macrophage infiltration in experimental nephritis; however, the role of OPN in glomerular lesions, particularly crescent forma...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.1998.00748.x
更新日期：1998-01-01 00:00:00
abstract：BACKGROUND:Vascular endothelial growth factor (VEGF) and its receptors have been implicated in the pathogenesis of diabetic nephropathy. The objective of this study was to determine whether alterations of the plasma and urinary VEGF and sFLT-1 levels were related to the stages and risk factors of diabetic nephropathy. ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1111/j.1523-1755.2005.00067.x
更新日期：2005-01-01 00:00:00
abstract：:Glucocorticoid induced leucine zipper protein (GILZ) is an aldosterone-regulated protein that controls sodium transport in cultured kidney epithelial cells. Mice lacking GILZ have been reported previously to have electrolyte abnormalities. However, the mechanistic basis has not been explored. Here we provide evidence ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2016.10.038
更新日期：2017-05-01 00:00:00
abstract：:Steroid Resistant Nephrotic Syndrome (SRNS) in children and young adults has differing etiologies with monogenic disease accounting for 2.9-30% in selected series. Using whole exome sequencing we sought to stratify a national population of children with SRNS into monogenic and non-monogenic forms, and further define t...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2016.10.013
更新日期：2017-04-01 00:00:00
