Abstract:
BACKGROUND:Gene expression profiling of nephropathies may facilitate development of diagnostic strategies for complex renal diseases as well as provide insight into the molecular pathogenesis of kidney diseases. To test molecular based renal disease categorization, differential gene expression profiles were compared between control and hydronephrotic kidneys showing varying degrees of inflammation and fibrosis. METHODS:RNA expression profiles from 9 hydronephrotic and 3 control kidneys were analyzed using small macroarrays dedicated to genes involved in cell-cell contact, matrix turnover, and inflammation. In parallel, the degree of tubulointerstitial inflammation, fibrosis, and tubular atrophy using light microscopy and quantitative immunohistochemical parameters was determined. RESULTS:Hierarchic clustering and self-organizing maps led to a gene expression dendrogram with three distinct nodes representing the control group, four kidneys with high inflammation, and five kidneys giving high fibrosis scores. To evaluate the clinical applicability of the marker set, the expression of nine genes (6Ckine, IL-8, MMP-9, MMP-3, MMP-7, urokinase R, CXCR5, integrin-beta4, and pleiotrophin) was tested in tubulointerstitial samples from routine renal biopsies. Seven mRNA markers showed differential regulation in inflammation and fibrosis in the biopsy population. Clinical follow-up revealed stringent correlation between gene expression data and progression of renal disease, and allowed segregation of the biopsies into progressive or stable disease course based on gene expression profiles. CONCLUSION:This study suggests the feasibility of gene expression-based disease categorization in human nephropathies based on the extraction of marker gene sets.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Henger A,Kretzler M,Doran P,Bonrouhi M,Schmid H,Kiss E,Cohen CD,Madden S,Porubsky S,Gröne EF,Schlöndorff D,Nelson PJ,Gröne HJdoi
10.1111/j.1523-1755.2004.00499.xsubject
Has Abstractpub_date
2004-03-01 00:00:00pages
904-17issue
3eissn
0085-2538issn
1523-1755pii
S0085-2538(15)49783-2journal_volume
65pub_type
杂志文章abstract:BACKGROUND:Angiotensin type 1 (AT1) receptor-deficient mice (Agtr1-/-), which selectively lack both AT1A and AT1B receptor genes, are characterized by marked intrarenal vascular thickening. In the present study, we explored the possible involvement of the kinin-kallikrein system in the development of this renal vascula...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00574.x
更新日期:1999-08-01 00:00:00
abstract::A decreased expression of the fibroblast growth factor (FGF)-23 coreceptor Klotho was postulated as an early alteration in chronic kidney disease mineral and bone disorder, resulting in a compensatory increase in plasma FGF-23 levels. Klotho exists in both membrane-bound and secreted (sKlotho) forms, the latter of whi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.288
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:To chart the epidemiology of primary glomerular disease by means of a prospective regional study in the southern part of The Netherlands. METHODS:Experienced renal technicians collected renal biopsies, blood, and 24-hour urine samples at the bed site in each of the participating hospitals. The material was ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00835.x
更新日期:2004-09-01 00:00:00
abstract::The current study was undertaken to examine the effects of dithiothreitol (DDT), a sulfhydryl-reducing agent and heavy metal chelator, on the course of heavy metal-induced acute renal failure in the rat. Groups of rats in metabolic cages received uranyl nitrate (UN) alone, UN plus DTT, mercuric chloride (HgCl2) alone,...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.88
更新日期:1977-08-01 00:00:00
abstract:BACKGROUND:We hypothesized that increasing small solute clearance in peritoneal dialysis (PD) would lead to improvements in patient health-related quality of life (HRQOL). METHODS:Patients were randomized to a control group [standard 4 x 2 L continuous ambulatory peritoneal dialysis (CAPD)] and an intervention group (...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1523-1755.2005.00175.x
更新日期:2005-03-01 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
abstract::The loss of interstitial capillaries is a feature of several experimental models of renal disease and this contributes to secondary kidney injury. Angiopoietin-1 is a secreted growth factor which binds to Tie-2 present on endothelia to enhance cell survival thereby stabilizing capillary architecture in-vitro. Previous...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.179
更新日期:2008-08-01 00:00:00
abstract::In uremic patients resistance to the action of insulin has been documented, but it is not known at what stage of renal disease it appears. We therefore examined 29 patients with IgA glomerulonephritis (IgAGN) and 21 patients with adult polycystic kidney disease (ADPKD) in different stages of renal failure, and in addi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00898.x
更新日期:1998-05-01 00:00:00
abstract:BACKGROUND:Dialysis efficiency has a great influence on the outcome of patients. Few data are available on the removal of solutes with molecular weights higher than urea and creatinine. The aim of our study was to assess the transport and the removal of substances with molecular weights up to 15 kD and to evaluate the ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00216.x
更新日期:2002-03-01 00:00:00
abstract:BACKGROUND:Since the cloning of the gene for autosomal dominant polycystic kidney disease type 2 (PKD2), approximately 40 different mutations of that gene have been reported to be associated with the disease. The relationship between the PKD2 genotype and phenotype, however, remains unclear. METHODS:Detailed clinical ...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1046/j.1523-1755.2000.00989.x
更新日期:2000-04-01 00:00:00
abstract::Fifty-one adults with HIV infection, including 20 chronic hemodialysis patients with superimposed HIV infection and 31 patients with HIV-associated nephropathy requiring chronic maintenance hemodialysis were followed to evaluate survival on outpatient dialysis in relation to the clinical stage of the HIV infection. Re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.172
更新日期:1988-08-01 00:00:00
abstract::We investigated the effects of epidermal growth factor (EGF) and arginine vasopressin (AVP) on Raf-1-MAP kinase cascade, including Raf-1-kinase (Raf-1-K), MAP kinase kinase (MAPKK), MAP kinase (MAPK) and S6 kinase (S6K) in Madin-Darby canine kidney (MDCK) cells. In a dose-dependent manner (10(-10) M to 10(-6) M), EGF ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.346
更新日期:1995-09-01 00:00:00
abstract::We evaluated short- and long-term effects of high-dose recombinant human erythropoietin (rHuEPO) in kidney transplantation in a prospective double-blind, placebo-controlled study. Patients with chronic kidney disease following receipt of a deceased donor kidney allograft were randomized to 3 doses of 40,000 units rHuE...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/ki.2011.349
更新日期:2012-02-01 00:00:00
abstract::Isotomic fluid reabsorption (JV) of rat renal proximal tubules was examined by the shrinking droplet method in combination with simulatneous perfusion of blood capillaries. Sensitivity of JV measurement was improved by using each punctured tubule for control measurements: 1) Parathyroid hormoen (PTH) on the contralumi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.12
更新日期:1977-02-01 00:00:00
abstract::In six healthy males on a fixed sodium/potassium (Na/K) intake, we studied the relation between plasma K and urine K and Na excretion after an oral K load. Studies were repeated during fludrocortisone (0.5 mg bid) or spironolactone (50 mg qid), that is, after escape from the Na-retaining and Na-excreting effects of th...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.235
更新日期:1988-11-01 00:00:00
abstract::The role of glutathione (GSH) in the preservation of renal function and the pathogenesis of renal injury has been investigated using the isolated perfused rat kidney as a model. In kidneys perfused for 80 min with 5 mM glucose as the only exogenous substrate, tissue GSH becomes depleted, renal function deteriorates, a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.142
更新日期:1983-08-01 00:00:00
abstract::Neuropilin1 (Nrp1) is a co-receptor best known to regulate the development of endothelial cells and is a target of anticancer therapies. However, its role in other vascular cells including pericytes is emergent. The kidney is an organ with high pericyte density and cancer patients develop severe proteinuria following ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.10.010
更新日期:2017-04-01 00:00:00
abstract::Alterations in red blood cell sodium (Na) transport have been described in chronic renal failure. This study examines the possible impact of uremia on two ouabain-insensitive pathways, the Na/H antiporter and the Cl-/NaCO3- anion exchanger. The Vmax of Na/H antiporter measured as Na influx driven by outward H gradient...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.283
更新日期:1993-09-01 00:00:00
abstract::The highly amiloride-sensitive epithelial sodium channel (ENaC) is an apical membrane constituent of cells of many salt-absorbing epithelia. In the kidney, the functional relevance of ENaC expression has been well established. ENaC mediates the aldosterone-dependent sodium reabsorption in the distal nephron and is inv...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1046/j.1523-1755.2000.00968.x
更新日期:2000-04-01 00:00:00
abstract::Uracil ribonucleotide-sugars and aminosugars are required for glomerular basement membrane (GBM) biosynthesis. Since these nucleotides are metabolic derivatives of uridine 5'-triphosphate (UTP), we have studied the cellular pools of uridine 5'-diphosphoglucose (UDPG), uridine 5'-diphosphoglucuronic acid (UDPGA), uridi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.146
更新日期:1986-07-01 00:00:00
abstract:BACKGROUND:The beneficial effect of blood transfusions before cadaveric renal transplantation on allograft survival, although previously well documented, has become controversial in light of their adverse effects. Recently, it has been suggested that their clinical benefits are due to HLA-DR sharing between the blood d...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1046/j.1523-1755.2001.00805.x
更新日期:2001-07-01 00:00:00
abstract:INTRODUCTION:Transforming growth factor-beta (TGF-beta) is known to play a pivotal role in the regulation of extracellular matrix (ECM) accumulation. Since diabetic nephropathy (DMN) is characterized by basement membrane thickening and mesangial expansion, control of ECM deposition is believed to be important in the pa...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00919.x
更新日期:2003-05-01 00:00:00
abstract::To evaluate the underlying mechanism of the putative renal protective effects of angiotensin converting enzyme (ACE) inhibitors, the modulatory action of captopril on the angiotensin II (Ang II) and platelet-derived growth factor (PDGF)-induced increase of cytosolic free calcium concentration ([Ca2+]i) was investigate...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.323
更新日期:1994-09-01 00:00:00
abstract::A new study in dialysis patients demonstrates that more than one-third of rehospitalizations within 30 days of discharge occur within the first week, and these rehospitalizations are associated with worse survival. Imposing a penalty on the dialysis provider for these rehospitalizations, as mandated by the Hospital Re...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2017.04.046
更新日期:2017-10-01 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:BACKGROUND:Advanced glycation of proteins and their attendant advanced glycation end products (AGEs) contribute to the complications associated with diabetes mellitus or uremia. Regulatory mechanisms of AGE formation in vivo remain an issue of particular interest. We investigated a role of the glyoxalase detoxification...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00051.x
更新日期:2001-12-01 00:00:00
abstract::Vitamin D deficiency is common in patients with chronic kidney disease after renal transplantation. Vitamin D, essential for mineral and bone metabolism, also has myriad beneficial autocrine effects on intact immune responses and defense against infection, as well as suppression of malignant changes. Supplementation w...
journal_title:Kidney international
pub_type: 评论,杂志文章,评审
doi:10.1038/ki.2008.492
更新日期:2009-03-01 00:00:00
abstract::[Arg(8)]-vasopressin (AVP) has several functions via its three distinct receptors, V1a, V1b, and V2. The V1a vasopressin receptor (V1aR) is expressed in blood vessels and involved in vascular contraction. Recently, we generated V1a receptor-deficient (V1aR(-/-)) mice and found that they were hypotensive. In addition, ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2009.319
更新日期:2009-11-01 00:00:00
abstract::Chronic cyclosporine (CsA) nephrotoxicity is a major complication of heart, bone marrow, and renal transplantation, and is characterized in humans by striped interstitial fibrosis, tubular dilatation and atrophy, and hyalinization of hilar arterioles. This last feature is highly specific for cyclosporine injury and ha...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.311
更新日期:1995-08-01 00:00:00
abstract::The kidney is influenced by circadian rhythms and is entrained to the sleep-wake cycle allowing anticipation of the metabolic and physiological demands of the kidney throughout a 24-hour cycle. Although sleep disruption has been studied extensively in cardiovascular and metabolic disease, its association with chronic ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2015.12.048
更新日期:2016-06-01 00:00:00