Abstract:
:Diabetic nephropathy is a growing health concern with characteristic sterile inflammation. As the underlying mechanisms of this inflammation remain poorly defined, specific therapies targeting sterile inflammation in diabetic nephropathy are lacking. Intriguingly, an association of diabetic nephropathy with inflammasome activation has recently been shown, but the pathophysiological relevance of this finding remains unknown. Within glomeruli, inflammasome activation was detected in endothelial cells and podocytes in diabetic humans and mice and in glucose-stressed glomerular endothelial cells and podocytes in vitro. Abolishing Nlrp3 or caspase-1 expression in bone marrow-derived cells fails to protect mice against diabetic nephropathy. Conversely, Nlrp3-deficient mice are protected against diabetic nephropathy despite transplantation of wild-type bone marrow. Pharmacological IL-1R antagonism prevented or even reversed diabetic nephropathy in mice. Mitochondrial reactive oxygen species (ROS) activate the Nlrp3 inflammasome in glucose or advanced glycation end product stressed podocytes. Inhibition of mitochondrial ROS prevents glomerular inflammasome activation and nephropathy in diabetic mice. Thus, mitochondrial ROS and Nlrp3-inflammasome activation in non-myeloid-derived cells aggravate diabetic nephropathy. Targeting the inflammasome may be a potential therapeutic approach to diabetic nephropathy.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Shahzad K,Bock F,Dong W,Wang H,Kopf S,Kohli S,Al-Dabet MM,Ranjan S,Wolter J,Wacker C,Biemann R,Stoyanov S,Reymann K,Söderkvist P,Groß O,Schwenger V,Pahernik S,Nawroth PP,Gröne HJ,Madhusudhan T,Isermann Bdoi
10.1038/ki.2014.271subject
Has Abstractpub_date
2015-01-01 00:00:00pages
74-84issue
1eissn
0085-2538issn
1523-1755pii
S0085-2538(15)30024-7journal_volume
87pub_type
杂志文章abstract::Dysregulated production of adipocytokines may be involved in the development of atherosclerotic cardiovascular disease in metabolic syndrome and chronic kidney disease (CKD) associated with metabolic syndrome. The aim of this study was to determine the effects of treatment with angiotensin II (Ang II) type-1 receptor ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001810
更新日期:2006-11-01 00:00:00
abstract::Leukocytes play a major role in the development and progression of autoimmune diseases. We measured gene expression differences in leukocytes from patients that were antineutrophil cytoplasmic autoantibody (ANCA) positive, patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), and healthy donor...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002371
更新日期:2007-10-01 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::The relationship of protein intake to urinary oxalate and glycolate excretion was examined in a large cohort (N = 101) of normal individuals on self-selected diets and in 11 individuals on controlled protein diets. On self-selected diets no correlation was detected between protein intake and urinary oxalate or glycola...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.253
更新日期:1993-08-01 00:00:00
abstract::Vitamin D hydroxylated at carbon 25 (25(OH)D) is generally recognized as a precursor of active vitamin D. Despite its low affinity for the vitamin D receptor (VDR), both deficient and excessive 25(OH)D levels are associated with poor clinical outcomes. Here we studied direct effects of 25(OH)D3 on the kidney using 25(...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.210
更新日期:2015-11-01 00:00:00
abstract::A genome-wide association scan of the Genetics of Kidneys in Diabetes (GoKinD) collections identified four novel susceptibility loci, located on chromosomes 7p14.3, 9q21.32, 11p15.4, and 13q33.3 associated with type 1 diabetic nephropathy. A recent evaluation of these loci in Japanese patients with type 2 diabetes sup...
journal_title:Kidney international
pub_type: 杂志文章,meta分析
doi:10.1038/ki.2011.64
更新日期:2011-07-01 00:00:00
abstract:BACKGROUND:Increased venous pressure (VP) and decreased access flow (Qa) are predictors of dialysis access graft thrombosis. VP is easily obtainable. Qa assessment requires a special device and takes more time. The aims of our randomized multicenter studies were to compare outcome in patients with grafts monitored by V...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1523-1755.2001.0590041551.x
更新日期:2001-04-01 00:00:00
abstract::The goals of the present study were twofold: first, to assess the renal excretory and hormonal responses to chronic water restriction in dogs whose sodium retaining mechanisms had been stimulated through dietary sodium (Na+) deprivation; second, to determine the mediator(s) of the natriuresis which was observed with w...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.121
更新日期:1986-06-01 00:00:00
abstract:BACKGROUND:Bone marrow reconstitution using genetically-modified hematopoietic stem cells has been reported to confer resistance to inflammation and prevent renal injury in glomerulonephritis. Although this strategy has potentials for clinical use, taking hematopoietic stem cells from bone marrow is highly stressful fo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00046.x
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2002.kid587.x
更新日期:2002-10-01 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::Neutrophil gelatinase-associated lipocalin (Ngal) is a biomarker for acute and chronic renal injuries, including polycystic kidney disease (PKD). However, the effect of Ngal on PKD progression remains unexplored. To study this, we generated 3 strains of mice with different expression levels of Ngal within an establish...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.09.005
更新日期:2017-02-01 00:00:00
abstract::To investigate the direct toxicity of human Bence Jones protein (BJP), individual nephrons of male Sprague-Dawley rats were perfused in vivo at 20 nl/min with an artificial tubule fluid (ATF) that contained no protein, a human kappa BJP (5 g/dl), or bovine serum albumin (5 g/dl), and proximal convoluted tubule functio...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.286
更新日期:1987-12-01 00:00:00
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journal_title:Kidney international
pub_type: 评论,杂志文章,评审
doi:10.1038/ki.2008.189
更新日期:2008-07-01 00:00:00
abstract:BACKGROUND:Evaluation of beta2-microglobulin (beta2m) removal during hemodialysis using predialysis and immediate postdialysis plasma concentrations is only valid in the absence of postdialysis rebound. Postdialysis rebound of beta2m has not been studied extensively, and its importance in the determination of beta2m cl...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1046/j.1523-1755.1999.00669.x
更新日期:1999-10-01 00:00:00
abstract::Recent studies have greatly expanded our knowledge of initial events that lead to epithelial cell polarity. Epithelial polarity is defined, in part, by apical cell-cell tight junctions that separate the plasma membrane into the apical domain and the basolateral domain, as well as the zonula adherens that mediate inter...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5002579
更新日期:2007-12-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1986.13
更新日期:1986-01-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.518
更新日期:2010-04-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000433
更新日期:2006-06-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00804.x
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journal_title:Kidney international
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journal_title:Kidney international
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doi:10.1046/j.1523-1755.2000.00883.x
更新日期:2000-02-01 00:00:00
abstract:BACKGROUND:The clinical demographics of chronic dialysis patients are changing worldwide. However, long-term data from regional dialysis registries have not yet been analyzed and reported. METHODS:The Okinawa Dialysis Study (OKIDS) registry included all chronic dialysis patients treated in Okinawa, Japan, since 1971. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00147.x
更新日期:2002-02-01 00:00:00
abstract:BACKGROUND:Hyperphagic obese Zucker rats develop glomerular injury and die of renal disease, an outcome prevented by food restriction at an early age. We examined the effects of food restriction imposed at different ages on systemic, renal hemodynamic, and hormonal changes to gain insight into the mechanisms of obesity...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00412.x
更新日期:2002-07-01 00:00:00
abstract::A high frequency (25%) of anti-hepatitis C virus (HCV) antibodies is observed in French hemodialyzed patients; this is associated with detectable viremia in 85% and results in chronic hepatitis in more than 90%. We conducted a pilot study to examine the tolerance and efficacy of alpha-2b Interferon therapy upon HCV in...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.198
更新日期:1995-05-01 00:00:00
abstract:BACKGROUND:It is known that chronic renal insufficiency (CRI) patients with gout may have subtle lead poisoning. In addition, gout episodes frequently aggravate progressive renal insufficiency because of the use of nephrotoxic drugs and urate deposition. Our study was arranged to evaluate the causal effect of environme...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1523-1755.2001.00795.x
更新日期:2001-07-01 00:00:00
abstract:BACKGROUND:Somatic cells in vitro have a finite life expectancy before entering a state of senescence, but it is unclear whether this state occurs in vivo in kidney development, growth, and aging. We previously showed that human kidney cortex displays telomere shortening with age. In this study, we compared the structu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00032.x
更新日期:2003-06-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00100.x
更新日期:2000-06-01 00:00:00
abstract::Diagnosis and treatment of atherosclerotic renal artery stenosis (ARAS) in the elderly is a never-ending challenge for every nephrologist. Kalra et al. report that adjusted hazard ratios for ARAS increased threefold from 1992 to 2004 in 16 million United States Renal Data System participants aged 66 years or older. Ho...
journal_title:Kidney international
pub_type: 信件
doi:10.1038/ki.2009.326
更新日期:2010-01-01 00:00:00
abstract::Effect of insulin-like growth factor-1 (IGF) on the synthesis of glomerular proteoglycans (PGs) in an ex vivo recirculating organ perfusion system was investigated. Kidneys were perfused with a medium (approximately 80 ml) containing [35S]-sulfate (250 microCi/ml) and IGF (62.5 to 625 ng/ml). After radiolabeling, a sm...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.188
更新日期:1992-05-01 00:00:00