Abstract:
:Atypical hemolytic uremic syndrome and thrombotic thrombocytopenic purpura have traditionally been considered separate entities. Defects in the regulation of the complement alternative pathway occur in atypical hemolytic uremic syndrome, and defects in the cleavage of von Willebrand factor (VWF)-multimers arise in thrombotic thrombocytopenic purpura. However, recent studies suggest that both entities are related as defects in the disease-causing pathways overlap or show functional interactions. Here we investigate the possible functional link of VWF-multimers and the complement system on endothelial cells. Blood outgrowth endothelial cells (BOECs) were obtained from 3 healthy individuals and 2 patients with Type 3 von Willebrand disease lacking VWF. Cells were exposed to a standardized complement challenge via the combination of classical and alternative pathway activation and 50% normal human serum resulting in complement fixation to the endothelial surface. Under these conditions we found the expected release of VWF-multimers causing platelet adhesion onto BOECs from healthy individuals. Importantly, in BOECs derived from patients with von Willebrand disease complement C3c deposition and cytotoxicity were more pronounced than on BOECs derived from normal individuals. This is of particular importance as primary glomerular endothelial cells display a heterogeneous expression pattern of VWF with overall reduced VWF abundance. Thus, our results support a mechanistic link between VWF-multimers and the complement system. However, our findings also identify VWF as a new complement regulator on vascular endothelial cells and suggest that VWF has a protective effect on endothelial cells and complement-mediated injury.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Noone DG,Riedl M,Pluthero FG,Bowman ML,Liszewski MK,Lu L,Quan Y,Balgobin S,Schneppenheim R,Schneppenheim S,Budde U,James P,Atkinson JP,Palaniyar N,Kahr WH,Licht Cdoi
10.1016/j.kint.2016.03.023subject
Has Abstractpub_date
2016-07-01 00:00:00pages
123-34issue
1eissn
0085-2538issn
1523-1755pii
S0085-2538(16)30077-1journal_volume
90pub_type
杂志文章abstract::Despite the high cardiovascular risk associated with chronic kidney disease, a recent systematic review confirmed that patients with kidney disease remain underrepresented in cardiovascular trials. Two ongoing trials are assessing the risk:benefit of aggressive evaluation and intervention for ischemic heart disease in...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.03.012
更新日期:2016-06-01 00:00:00
abstract::Recent studies of timing of dialysis initiation have challenged the recent trend to earlier initiation of therapy. The observed outcomes though are a consequence of the balance between the risks of advanced uremia versus the inherent dangers relating to dialysis therapy itself. Many of these risks are inherent in how ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2012.133
更新日期:2012-08-01 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
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更新日期:2001-04-01 00:00:00
abstract::The involvement of sodium/potassium-ATPase in regulating parathyroid hormone (PTH) secretion is inferred from in vitro studies. Recently, the α-klotho-dependent rapid recruitment of this ATPase to the parathyroid cell plasma membrane in response to low extracellular calcium ion was suggested to be linked to increased ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.501
更新日期:2011-04-01 00:00:00
abstract::Renal ischemia-reperfusion injury is a leading cause of acute kidney injury; the pathogenesis of which remains poorly understood and effective therapies are still lacking. Here we tested whether microRNAs, identified as critical regulators of cell health and disease, are involved in this process. We found that miR-17-...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.07.017
更新日期:2017-01-01 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
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00433.x
更新日期:1999-05-01 00:00:00
abstract::Diabetes mellitus is associated with natriuresis, whereas estrogen has been shown to be renoprotective in diabetic nephropathy and may independently regulate renal sodium reabsorption. The aim of this study was to determine the effects of 17-beta estradiol (E(2)) replacement to diabetic, ovariectomized (OVX) female ra...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000140
更新日期:2006-02-01 00:00:00
abstract::Cystinuria is a common inherited aminoaciduria that leads to recurrent cystine nephrolithiasis. Mutations in a gene encoding a renal amino acid transporter (SLC3A1) have been identified in patients with cystinuria establishing one molecular cause for the disease. To facilitate systematic screening of this gene for mut...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.258
更新日期:1997-06-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.91
更新日期:1994-03-01 00:00:00
abstract::Apoptosis mediated by verotoxins (VTs) has been identified in a renal carcinoma cell line, ACHN cells, which are an in vitro model of renal tubular epithelial cells. ACHN cells express the renal tubular marker CD24 as well as globotriaosyl ceramide/CD77, the receptor for VTs. VT binding to the ACHN cell surface was co...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00939.x
更新日期:1998-06-01 00:00:00
abstract:BACKGROUND:The fibrinolytic system plays an important role in degrading fibrin-rich thrombi and in vascular and tissue remodeling. Elevated levels of plasminogen activator inhibitor-1 (PAI-1) can reduce the efficiency of the endogenous fibrinolytic system. Angiotensin (Ang) has been shown to regulate PAI-1 expression v...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00160.x
更新日期:2000-07-01 00:00:00
abstract::Mutations in the complement regulatory proteins are associated with several different diseases. Although these mutations cause dysregulated alternative pathway activation throughout the body, the kidneys are the most common site of injury. The susceptibility of the kidney to alternative pathway-mediated injury may be ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.02.036
更新日期:2016-07-01 00:00:00
abstract::Urinary proteomics is a promising tool for biomarker investigation, particularly in complex kidney diseases. Fabris and colleagues report that urinary laminin subunit alpha-2 is a potential diagnostic marker of medullary sponge kidney (MSK) disease by using a label-free quantitative proteomics platform and a clinicall...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.10.032
更新日期:2017-02-01 00:00:00
abstract::Proteinuric diabetic patients have an increased risk of cardiovascular disease and almost always have hypertension. In the early stages of diabetic renal disease (microalbuminuria) when renal function is well preserved, systemic arterial blood pressure is already elevated compared to insulin-dependent diabetic patient...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1994.56
更新日期:1994-02-01 00:00:00
abstract::Recent studies including the current article by Sawinski et al. demonstrate that hepatitis C virus (HCV) infection is associated with worse outcomes in kidney transplant recipients with and without HIV infection. We comment on the significance of these findings in the context of newer options for the treatment of HCV ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2015.180
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND:The impact of obesity on survival in end-stage renal disease (ESRD) patients as related to dialysis modality (i.e., a direct comparison of hemodialysis with peritoneal dialysis) has not been assessed adjusting for differences in medication use, follow-up > or =2 years, or accounting for changes in dialysis m...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00385.x
更新日期:2004-02-01 00:00:00
abstract:BACKGROUND:Cardiovascular disease is known to be the most important complication among patients with renal failure, and oxidative stress has been proposed to play a major role as the source of such complications. Human serum albumin (HSA) is composed of human mercaptoalbumin (HMA) with cysteine residues having reducing...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00969.x
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND:Many studies have reported that blocking the renin-angiotensin-system (RAS) with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker in the patient with diabetes mellitus leads to an increase in renal plasma flow (RPF), no change in glomerular filtration rate (GFR), and a fall...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1046/j.1523-1755.2003.00701.x
更新日期:2003-01-01 00:00:00
abstract::Adhesion of calcium oxalate (CaOx) crystals to kidney cells may be a key event in the pathogenesis of kidney stones associated with marked hyperoxaluria. Previously, we found that 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), isolated from a traditional medicinal herb, reduced CaOx crystal adhesion to renal epithelial ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.458
更新日期:2011-03-01 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
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.206
更新日期:2013-11-01 00:00:00
abstract::Hypertriglyceridemia in nephrotic (NS) and Nagase analbuminemic rats (Analb) results from reduced triglyceride clearance. NS and Analb have reduced or absent albumin, reduced plasma oncotic pressure (pi), but Analb lack proteinuria. The heparin releasable lipoprotein lipase (LpL) pool in both models is greatly reduced...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000318
更新日期:2006-08-01 00:00:00
abstract::The rate of myofibrillar protein degradation was measured by 3-methylhistidine (3MH) release in moderately uremic and sham-operated control rats. The rats were studied in the fed state or after 24 and 48 hours of fasting. When fed, both uremic and control rats gained weight at the same rate. During 48 hours of fasting...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.141
更新日期:1981-09-01 00:00:00
abstract::Nephropathic cystinosis is a multisystem autosomal recessive disease caused by cystine accumulation, which is usually treated by oral cysteamine. In order to determine long-term effects of this therapy, we enrolled 86 adult patients (mean age 26.7 years) diagnosed with nephropathic cystinosis, 75 of whom received cyst...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.277
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:We developed an electroporation-mediated gene transfer method targeting glomerular mesangial cells. Injecting DNA solution via renal artery followed by electric pulses using tweezers-type electrodes could result in efficient transfection in mesangial cells. Therefore, this gene transfer system opened a feasi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00777.x
更新日期:2004-08-01 00:00:00
abstract:BACKGROUND:Patients on continuous ambulatory peritoneal dialysis (CAPD) are dependent on residual renal function for solute and water clearances, and this declines with time on dialysis. Loop diuretics have been postulated to slow this decline. METHODS:Sixty-one patients new to dialysis were randomly assigned to eithe...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1523-1755.2001.0590031128.x
更新日期:2001-03-01 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::Erythropoietin (Epo) is essential for erythropoiesis and is mainly produced by the fetal liver and the adult kidney following hypoxic stimulation. Epo regulation is commonly studied in hepatoma cell lines, but differences in Epo regulation between kidney and liver limit the understanding of Epo dysregulation in polycy...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.08.043
更新日期:2019-02-01 00:00:00
abstract::Rare mutations in the LRP2 gene encoding for the endocytic receptor megalin cause developmental abnormalities and kidney disease. However, the mechanisms governing the dysfunction of mutant megalin remain unclear. A new study utilizing patient-derived induced pluripotent stem cells is now putting the endolysosomal sys...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.04.033
更新日期:2020-07-01 00:00:00