Abstract:
BACKGROUND:Candidate biomarkers for vasculopathy in systemic lupus erythematosus (SLE) include circulating endothelial cells and the recently identified endothelial protein C receptor (EPCR) which, when shed, promotes a thrombotic diathesis. This study sought correlation between plasma levels of soluble EPCR and disease manifestation/severity, with a focus on lupus nephritis. METHODS:In 81 SLE patients (evaluated cross-sectionally and longitudinally) and 59 healthy controls, levels of soluble EPCR and soluble E-selectin were assessed by sandwich enzyme-linked immunosorbent assay (ELISA), circulating endothelial cells isolated by immunomagnetic separation, and EPCR gene polymorphisms determined. Mechanisms of vascular injury were addressed in vitro in human aortic endothelial cells (HAEC) cultured in the presence and absence of interferon-gamma (IFN-gamma). RESULTS:The mean level of soluble EPCR was significantly higher in SLE patients (263 +/- 13 ng/mL) than controls (174 +/- 11 ng/mL) (P < 0.0001). Patients with active or past renal involvement had significantly higher mean soluble EPCR levels (306 +/- 21 ng/mL) (N= 40) than patients without nephritis (228 +/- 14 ng/mL) (N= 41) (P= 0.0033). Mean soluble EPCR correlated positively with serum creatinine (R= 0.3429, P < 0.0001). The prevalence of the enhanced-shedding EPCR polymorphism A6936G was higher in SLE (41%) (N= 27) than controls (7%) (N= 29) (P= 0.0039). Patient and control plasma were also interrogated for soluble E-selectin, a comparator plasma marker. The results suggest that soluble E-selectin and soluble EPCR are not equivalent end points of vasculopathy and endothelial perturbation in SLE. Although in SLE patients the absence or diminished expression of membrane EPCR on circulating endothelial cells varied, the rare circulating endothelial cells detected in controls invariably expressed membrane-bound EPCR. IFN-gamma-treated HAEC expressed less membrane-bound EPCR [133 relative fluorescence units (rfu)] than untreated HAEC (275 rfu); more soluble EPCR was detected in IFN-gamma-treated (1.1 ng/10(6) cells) than untreated HAEC (0.65 ng/10(6) cells) (P= 0.027). CONCLUSION:The results obtained from this cross-sectional/longitudinal study support the hypothesis that the vascular dysfunction characteristic of SLE may be related to a dramatically altered distribution of EPCR, both soluble and membrane-bound forms.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Sesin CA,Yin X,Esmon CT,Buyon JP,Clancy RMdoi
10.1111/j.1523-1755.2005.00385.xsubject
Has Abstractpub_date
2005-07-01 00:00:00pages
110-20issue
1eissn
0085-2538issn
1523-1755pii
S0085-2538(15)50818-1journal_volume
68pub_type
杂志文章abstract::Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) commonly results in glomerulonephritis, in which neutrophils and monocytes have important roles. The heterodimer calprotectin (S100A8/S100A9, mrp8/14) is a Toll-like receptor-4 ligand found in neutrophils and monocytes and is elevated in inflammatory...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.2
更新日期:2013-06-01 00:00:00
abstract::Fibroblast growth factor-23 (FGF23), a regulator of mineral metabolism, has been linked to cardiovascular disease in chronic kidney disease. As community-based data of the longitudinal association between FGF23 and cardiovascular events are lacking, we investigated a possible relationship in 727 men of the Uppsala Lon...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.327
更新日期:2013-01-01 00:00:00
abstract::The purpose of this prospective, angiographically controlled study was to determine the diagnostic value of color Doppler sonography with two differing approaches of scanning in patients with clinical clues for renal artery stenosis (RAS). In 135 hypertensive patients peak systolic velocity in the main renal arteries ...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1996.440
更新日期:1996-10-01 00:00:00
abstract::To assess the comparative effects of hemodialysis with acetate versus bicarbonate base on left ventricular systolic function, we performed M-mode echocardiography on 36 patients prior to and immediately following 4-hr maintenance hemodialysis. Patients were initially dialyzed against either sodium acetate or sodium bi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.78
更新日期:1985-05-01 00:00:00
abstract::The cellular redox state is altered in a number of pathological conditions, including various forms of glomerular injury and diabetes. For example, glucose, via the pentose phosphate pathway generates NADPH, which maintains glutathione (GSH) (part of a major intracellular reducing system) in its reduced state. GSH in ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.286
更新日期:1994-08-01 00:00:00
abstract::Studies were undertaken to examine the mechanism whereby changes in intraluminal flow rates after reabsorption in the isolated perfused proximal tubule of the rabbit. All protocols employed the technique of in vitro perfusion of isolated segments of the proximal convoluted tubule. Stepwise elimination of d-glucose and...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.3
更新日期:1977-01-01 00:00:00
abstract::The present experiments were performed to examine the effect of variation in protein intake on renal function and morphology in the non-clipped kidneys of Goldblatt hypertensive rats. After renal artery clipping, rats were put on diets containing 5 (LP), 17.5 (NP), or 51% (HP) protein. After 4 to 5 weeks, all rats had...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.30
更新日期:1986-02-01 00:00:00
abstract::Acute elevations in intracellular adenosine 3',5'-cyclic monophosphate (cAMP) concentrations are known to increase ionic chloride permeability in diverse tissues. To determine if chronic endogenous increases in cAMP are associated with sustained alterations in membrane ionic permeabilities, renal cortical brush border...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.290
更新日期:1992-08-01 00:00:00
abstract::Hyperinsulinemia can contribute to hypertension through effects on sodium transport. To test whether the stimulatory effect of insulin on renal proximal tubule sodium transport is preserved in insulin resistance, we compared the effects of insulin on abdominal adipocytes and proximal tubules in rats and humans. Insuli...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.351
更新日期:2015-03-01 00:00:00
abstract::Acute kidney injury (AKI) severe enough to require dialysis is increasing and associated with high mortality, yet robust information about temporal epidemiology of AKI requiring dialysis in England is lacking. In this retrospective observational study of the Hospital Episode Statistics (HES) data set covering the enti...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.234
更新日期:2015-11-01 00:00:00
abstract::Bovine serum albumin (BSA, pI 4.9) was maleylated to yield highly anionic MBSA (pI 3.0). Maleylation of BSA lead to an expansion of molecular size of native BSA from an effective molecular radius (EMR) of 37 A to 57 A for MBSA as assessed by gel filtration chromatography. MBSA, but not BSA, bound to the peripheral cap...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.161
更新日期:1988-08-01 00:00:00
abstract::Targeted therapies and immune checkpoint inhibitors have advanced the treatment landscape of Renal Cell Carcinoma (RCC) over the last decade. While checkpoint inhibitors have demonstrated survival benefit and are currently approved in the front-line and second-line settings, primary and secondary resistance is common....
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2020.08.028
更新日期:2021-01-01 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:BACKGROUND:Previous reports have shown the presence of erythrogenic toxin type B (ETB), apoptosis, proliferation, and leukocyte infiltration in biopsies from patients with acute poststreptococcal glomerulonephritis (APSGN). METHODS:Attempting to correlate the apoptotic and proliferative events with the interaction of ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.059003950.x
更新日期:2001-03-01 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:Impaired reproductive function accompanies chronic renal insufficiency (uremia) in both the human and experimental animal. Clinical hypogonadism occurs in both genders. The present studies were designed to investigate possible anti-ovulatory effects of uremia in the female rat, a species that produces multip...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00203.x
更新日期:2000-08-01 00:00:00
abstract:BACKGROUND:Among the members of the small leucine-rich proteoglycan family, decorin, biglycan, and fibromodulin have been proposed to be potent modulators of transforming growth factor-beta (TGF-beta) activity, thereby playing an important role in the pathogenesis of fibrotic kidney diseases. Furthermore, decorin expre...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00317.x
更新日期:2000-10-01 00:00:00
abstract:BACKGROUND:Idiopathic nephrotic syndrome is a proteinuric disease secondary to the release of a nonidentified circulating glomerular permeability factor by T cells. Because specificities of T-cell activation in idiopathic nephrotic syndrome remain unknown, we evaluated transcriptional activation of T cells in nephrotic...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00322.x
更新日期:2005-06-01 00:00:00
abstract::Myeloproliferative neoplasms are clonal hematopoietic stem cell disorders that can produce an undefined glomerulopathy. To better characterize the glomerular disease associated with myeloproliferative neoplasms, we evaluated features of 11 patients with myeloproliferative neoplasm-related glomerulopathy that included ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.147
更新日期:2011-10-01 00:00:00
abstract::Compared to normal tissue, hyperplastic parathyroid glands of patients with chronic kidney disease on dialysis express lower levels of FGFR1 and Klotho proteins. Similar findings are reported in uremic rats with advanced chronic kidney disease. Moreover, in these animals, FGF23 administration fails to reduce PTH serum...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2009.512
更新日期:2010-03-01 00:00:00
abstract::Transplanted organs express allogeneic epitopes against which a recipient's immune system mounts a destructive response. In the absence of a reliable strategy for induction of donor-specific tolerance, therapeutic immunosuppression remains the best prospect to prevent rejection, but exposes recipients to increased ris...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.268
更新日期:2015-12-01 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::When patients develop acute kidney injury, a small fraction of them will develop end-stage renal disease later. The severity of renal impairment in the remaining patients is uncertain because studies have not carefully examined renal function over time or the precise timing of entry into a late stage of chronic kidney...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.332
更新日期:2009-11-01 00:00:00
abstract::To investigate whether alpha (alpha)-adrenoceptor agonists have a stimulatory effect on the expression of the angiotensinogen (Ang) gene in opossum kidney (OK) cells, we used OK 27 cells with a fusion gene containing the 5'-flanking regulatory sequence of the rat angiotensinogen gene fused with a human growth hormone ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.277
更新日期:1995-07-01 00:00:00
abstract::The processes of growth and remodeling that characterize growing bone are vulnerable to the biochemical effects of uremia. These processes are affected by the alterations in vitamin D metabolism and hyperparathyroidism that commonly occur with chronic renal insufficiency. Uremia interferes with cartilaginous developme...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1978.136
更新日期:1978-10-01 00:00:00
abstract::The biological action of calcitriol is mediated through a hormone-receptor complex interacting with nuclear chromatin. Interaction of the calcitriol receptor (VDR) with VDR response elements produces bioactive proteins which carry out the physiological actions of calcitriol. Since biological response to calcitriol app...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.252
更新日期:1994-07-01 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::Acute kidney injury (AKI) is associated with progression to advanced chronic kidney disease (CKD). We tested whether patients who survive AKI and are at higher risk for CKD progression can be identified during their hospital admission, thus providing opportunities to intervene. This was assessed in patients in the Dep...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.42
更新日期:2011-06-01 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::A protective role for sirtuin 6 (Sirt6) in the context of chronic renal injury is reported by Cai et al. in this issue of Kidney International. The mechanism is thought to be mediated by Sirt6's deacetylase activity, specifically on β-catenin target genes. This commentary discusses these results and the interaction be...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2019.09.022
更新日期:2020-01-01 00:00:00