Abstract:
:Severe sepsis is often accompanied by acute kidney injury (AKI) and albuminuria. Here we studied whether the AKI and albuminuria associated with lipopolysaccharide (LPS) treatment in mice reflects impairment of the glomerular endothelium with its associated endothelial surface layer. LPS treatment decreased the abundance of endothelial surface layer heparan sulfate proteoglycans and sialic acid, and led to albuminuria likely reflecting altered glomerular filtration permselectivity. LPS treatment decreased the glomerular filtration rate (GFR), while also causing significant ultrastructural alterations in the glomerular endothelium. The density of glomerular endothelial cell fenestrae was 5-fold lower, whereas the average fenestrae diameter was 3-fold higher in LPS-treated than in control mice. The effects of LPS on the glomerular endothelial surface layer, endothelial cell fenestrae, GFR, and albuminuria were diminished in TNF receptor 1 (TNFR1) knockout mice, suggesting that these LPS effects are mediated by TNF-α activation of TNFR1. Indeed, intravenous administration of TNF decreased GFR and led to loss of glomerular endothelial cell fenestrae, increased fenestrae diameter, and damage to the glomerular endothelial surface layer. LPS treatment decreased kidney expression of vascular endothelial growth factor (VEGF). Thus, our findings confirm the important role of glomerular endothelial injury, possibly by a decreased VEGF level, in the development and progression of AKI and albuminuria in the LPS model of sepsis in the mouse.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Xu C,Chang A,Hack BK,Eadon MT,Alper SL,Cunningham PNdoi
10.1038/ki.2013.286subject
Has Abstractpub_date
2014-01-01 00:00:00pages
72-81issue
1eissn
0085-2538issn
1523-1755pii
S0085-2538(15)56144-9journal_volume
85pub_type
杂志文章abstract:BACKGROUND:Segmental glomerular necrosis has been described in the biopsy material in a minority of patients with idiopathic IgA nephropathy in the oldest studies on this disease, but this marker of active capillaritis has received little attention in the subsequent literature, and its significance and relevance for th...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.059002682.x
更新日期:2001-02-01 00:00:00
abstract::The effect of intravenous infusion of angiotensin II on microvascular parameters of the renal microcirculation of rats was studied. With the aid of fluorescence microscopy and a high sensitivity video system we observed the passage of fluorescence-labeled erythrocytes through single glomerular capillaries on the surfa...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.4
更新日期:1985-01-01 00:00:00
abstract::Hypocalcemia, hyperphosphatemia, and resistance to the action of PTH are well characterized features in the setting of advanced chronic renal failure (CRF). Although the underlying mechanisms are ill-understood, clinical and experimental evidence points to both PTH receptor down-regulation and post-receptor abnormalit...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.79
更新日期:1994-02-01 00:00:00
abstract::Dysfunction and loss of podocytes (glomerular epithelial cells) are the hallmarks of focal segmental glomerulosclerosis (FSGS). In recent years, activation and proliferation of parietal epithelial cells (PECs) have been increasingly appreciated in FSGS. The functional role of PECs in FSGS is still a hotly debated issu...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2013.66
更新日期:2013-06-01 00:00:00
abstract::We sought to study glomerular pathophysiology in a model of IgA nephropathy (IgAN). Preliminary experiments with oral immunization indicated that Lewis rats had higher IgA levels and IgA/IgG ratios than Wistar, Fischer or Sprague-Dawley rats. Six groups of Lewis rats were studied: four continuously orally immunized fo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.268
更新日期:1992-07-01 00:00:00
abstract::The transition between the glomerulus and the proximal tubule was studied by light and electron microscopy in perfusion-fixed rabbit kidneys. In most nephrons a transitional segment of tubule occurred between the Bowman's capsule and the proximal tubule proper. This initial part of the tubule was lined by flattened ce...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1975.22
更新日期:1975-03-01 00:00:00
abstract:BACKGROUND:Low birth weight is an important risk factor for hypertension and unfavorable prognoses of a number of renal diseases. It is also associated with reduced kidney size and nephron number. A differentiation between the effects of low birth weight versus being born premature or small for gestational age has, how...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00451.x
更新日期:2005-08-01 00:00:00
abstract:BACKGROUND:Osteogenic protein-1/bone morphogenetic protein-7 (OP-1/BMP-7), a member of the transforming growth factor-beta superfamily, has been shown to prevent kidney damage from ischemia/reperfusion injury in rats. The molecular events involved in OP-1 action on kidney are not yet understood. METHODS:In this study,...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2000.00362.x
更新日期:2000-11-01 00:00:00
abstract::Potassium transport in the thick ascending limb is conducted by heterogeneous cells to opposite directions. Effects of glucocorticoids and mineralocorticoids on potassium transport of the rat medullary thick ascending limb (MTAL) were examined by in vitro microperfusion technique by measuring net potassium flux (JK), ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.122
更新日期:1995-03-01 00:00:00
abstract::Progressive renal vascular sclerosis is a key feature of chronic kidney disease (CKD). Adiponectin, an adipokine with potent anti-inflammatory and antiatherosclerotic properties, is associated with insulin resistance, type II diabetes and cardiovascular disease. In this study, we evaluated the predictive value of adip...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002191
更新日期:2007-06-01 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::The prevalence of raised Na+/Li+ countertransport (CT) activity (greater than 0.41 mmol/liter RBC/hr) was assessed in 185 consecutive insulin-dependent diabetic patients attending an outpatient diabetic clinic. Normoalbuminuria was defined as an overnight albumin excretion rate (AER) of less than 20 micrograms/min (N ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.134
更新日期:1992-04-01 00:00:00
abstract::It is known that in rodents recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor (rhIGF-1) increase renal mass. It is uncertain, however, whether renal mass increases in proportion to body growth, or whether renal growth is stimulated selectively. In 120 to 150 g female Sprague-Dawl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.376
更新日期:1993-12-01 00:00:00
abstract::The proportion of deceased donor kidneys procured for transplant but subsequently discarded has been growing steadily in the United States, but factors contributing to the rising discard rate remain unclear. To assess the reasons for and probability of organ discard we assembled a cohort of 212,305 deceased donor kidn...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.02.016
更新日期:2018-07-01 00:00:00
abstract::Lysyl oxidase like-2 (LOXL2) is an amine oxidase with both intracellular and extracellular functions. Extracellularly, LOXL2 promotes collagen and elastin crosslinking, whereas intracellularly, LOXL2 has been reported to modify histone H3, stabilize SNAIL, and reduce cell polarity. Although LOXL2 promotes liver and lu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.02.024
更新日期:2018-08-01 00:00:00
abstract::Podocytes are highly differentiated cells that play an important role in maintaining glomerular filtration barrier integrity; a function regulated by small GTPase proteins of the Rho family. To investigate the role of Rho A in podocyte biology, we created transgenic mice expressing doxycycline-inducible constitutively...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.472
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:Clinical studies have shown that the angiotensin-converting enzyme (ACE) inhibitors or angiotensin II (Ang II) receptor antagonists decrease proteinuria and slow the progression of nephropathy in diabetes, indicating that Ang II plays an important role in the development of nephropathy. We have previously re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00271.x
更新日期:1999-02-01 00:00:00
abstract::Although it is clear that genetic predispositions play a role in progressive glomerulosclerosis, identification of specific genes is difficult because of natural genetic heterogeneity among individuals. We have reported a differential susceptibility to progressive glomerulosclerosis after induction of experimental glo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001757
更新日期:2006-10-01 00:00:00
abstract::In a rat model of glomerular immune injury induced by administration of anti-glomerular basement membrane antibody and resembling human rapidly progressive glomerulonephritis, we explored whether activation of inducible nitric oxide synthase (iNOS) regulates synthesis of eicosanoids originating from cyclooxygenation o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00791.x
更新日期:1998-03-01 00:00:00
abstract::For decades, ill-defined autosomal dominant renal diseases have been reported, which originate from tubular cells and lead to tubular atrophy and interstitial fibrosis. These diseases are clinically indistinguishable, but caused by mutations in at least four different genes: UMOD, HNF1B, REN, and, as recently describe...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.72
更新日期:2014-09-01 00:00:00
abstract::Only some individuals carrying the high-risk APOL1 genotype go on to develop kidney disease phenotypes. In this issue of Kidney International, Nadkarni and colleagues report the associations of several biomarkers with renal outcomes in individuals with high-risk APOL1 genotypes. In the era of precision medicine, these...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2018.03.005
更新日期:2018-06-01 00:00:00
abstract::Dialysis patients have a high risk of cardiovascular disease. Cardiac rehabilitation is recommended in the general population as a standard component of care and covered by Medicare for those who have undergone coronary artery bypass grafting (CABG). Here we determined the impact of cardiac rehabilitation on Medicare ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.381
更新日期:2008-10-01 00:00:00
abstract::Factor H is a regulator of the alternative pathway of complement, and genetic studies have shown that patients with mutations in factor H are at increased risk for several types of renal disease. Pathogenic activation of the alternative pathway in acquired diseases, such as ischemic acute kidney injury, suggests that ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.115
更新日期:2011-07-01 00:00:00
abstract::We present a new hypothesis to explain the development of salt-dependent hypertension in humans. We propose that hypertension has two phases: an early phase in which elevations in blood pressure (BP) are mainly episodic and are mediated by a hyperactive sympathetic nervous or renin-angiotensin system, and a second pha...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1997.442
更新日期:1997-11-01 00:00:00
abstract::Administration of antibody, directed against glomerular basement membrane (GBM) heparan sulfate-proteoglycan, into a presensitized rat results in the induction of membranous nephropathy with subepithelial immune-complex deposits. In this investigation, we examined the mechanisms responsible for the formation of subepi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.166
更新日期:1988-08-01 00:00:00
abstract::Acid (H+) retention appears to contribute to progressive decline in glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD), including some patients without metabolic acidosis. Identification of patients with H+ retention but without metabolic acidosis could facilitate targeted alkali therapy; h...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.11.033
更新日期:2019-05-01 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::To maintain nitrogen equilibrium when prescribed a low protein diet (LPD), metabolic adaptations occur involving a reduction protein turnover, principally decreased muscle protein degradation. Studies suggest that in patients with chronic renal failure (CRF) uncomplicated by metabolic acidosis (MA), these adaptive res...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.275
更新日期:1991-10-01 00:00:00
abstract::Vascular sclerosis is often seen in renal biopsies. It is usually associated with diabetes mellitus, hypertension, smoking, etc. However, whether inherited thrombophilic states such as factor V gene mutation, prothrombin gene mutation, and methylenetetrahydrofolate reductase (MTHFR) gene mutation are associated with t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001551
更新日期:2006-08-01 00:00:00
abstract::We have previously shown that the activity of the Na-HCO3 cotransporter is stimulated by protein kinase C (PKC) activation, but the mechanism responsible for this effect is not clear. We have shown that cultured proximal tubule cells of the rabbit have DIDS-sensitive Na-HCO3 cotransporter activity as assessed by HCO3-...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.98
更新日期:1996-03-01 00:00:00