Abstract:
:Spleen tyrosine kinase (SYK) is an important component of the intracellular signaling pathway for various immunoreceptors. Inhibition of SYK has shown promise in preclinical models of autoimmune and glomerular disease. However, the description of SYK expression in human renal tissue, which would be desirable ahead of clinical studies, is lacking. Here we conducted immunohistochemical analysis for total and phosphorylated SYK in biopsy specimens from >120 patients with a spectrum of renal pathologies, including thin basement membrane lesion, minimal change disease, membranous nephropathy, IgA nephropathy, lupus nephritis, ANCA-associated glomerulonephritis, antiglomerular basement membrane disease, and acute tubular necrosis. We found significant SYK expression in proliferative glomerulonephritis and that glomerular expression levels correlated with presenting serum creatinine and histological features of disease activity that predict outcome in IgA nephropathy, lupus nephritis, ANCA-associated glomerulonephritis, and antiglomerular basement membrane disease. SYK was phosphorylated within pathological lesions, such as areas of extracapillary and endocapillary proliferation, and appeared to localize to both infiltrating leucocytes and to resident renal cells within diseased glomeruli. Thus SYK is associated with the pathogenesis of proliferative glomerulonephritides, suggesting that these conditions may respond to SYK inhibitor treatment.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
McAdoo SP,Bhangal G,Page T,Cook HT,Pusey CD,Tam FWdoi
10.1038/ki.2015.29subject
Has Abstractpub_date
2015-07-01 00:00:00pages
52-60issue
1eissn
0085-2538issn
1523-1755pii
S2157-1716(15)32139-0journal_volume
88pub_type
杂志文章abstract::Atherogenic lipoproteins and reactive oxygen species stimulate renin release from isolated juxtaglomerular (JG) cells. Here we assessed whether stimulation of renin release is mediated by formation of superoxide anion (O2-), and whether the effects of oxidized lipoproteins, like in many other biological systems, can b...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.30
更新日期:1997-01-01 00:00:00
abstract:BACKGROUND:In interstitial fibrosis, monocytes and myofibroblasts have been directly implicated in scarring, apoptosis, and tissue necrosis. While much has been done to explore the role of these cell types individually in fibrosis, the interactive dependency of monocytes and myofibroblasts has been only marginally expl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00871.x
更新日期:2003-04-01 00:00:00
abstract::Proximal tubular (PT) epithelial cells express MHC class II (Ia) antigens in immunologically-mediated renal injury. To study the role of PT as accessory cells, we generated several murine PT-like epithelial cell lines by transformation with origin-defective SV40 DNA. These transformed cell lines display typical alkali...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1990.46
更新日期:1990-02-01 00:00:00
abstract::Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a potent microvascular permeability-enhancing mediator as well as a selective mitogen for vascular endothelium. In this study, in situ hybridization and immunohistochemistry co-localized VPF mRNA and protein to glomerular v...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.441
更新日期:1992-12-01 00:00:00
abstract::Experiments were performed using a variety of methods to assess the functional status of different nephron populations following 45 min of renal ischemia in the rat. Micropuncture techniques revealed that SNGFR and reabsorption in the surface nephrons are only modestly reduced after ischemia, whereas kidney GFR and re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.122
更新日期:1983-07-01 00:00:00
abstract::Reducing proteinuria and blood pressure in chronic kidney disease (CKD) decreases rate of progression. Inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers is beneficial in reducing proteinuria but incomplete in suppressing aldosterone production a...
journal_title:Kidney international
pub_type: 评论,杂志文章,评审
doi:10.1038/sj.ki.5002007
更新日期:2006-12-01 00:00:00
abstract::Insulin resistance from chronic kidney disease (CKD) stimulates muscle protein wasting but mechanisms causing this resistance are controversial. To help resolve this, we used microarray analyses to identify initiators of insulin resistance in the muscles of mice with CKD, glucose intolerance, and insulin resistance. C...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.97
更新日期:2013-08-01 00:00:00
abstract::The adjuvanted hepatitis B vaccine, HB-AS04, elicits more rapid and persistent protective antibody concentrations than double doses of conventional recombinant vaccines in patients with renal insufficiency. We compared the immunogenicity, reactogenicity, and safety of the AS02(V)-adjuvanted hepatitis B vaccine HB-AS02...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/ki.2009.454
更新日期:2010-02-01 00:00:00
abstract::Long-term complications of continuous immunosuppression still remain a serious threat and are currently drawing the attention of transplant physicians. Wimmer et al. show that malignancy occurs approximately fourfold more frequently in renal-transplant recipients than in a normal control population. Besides immunosupp...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002306
更新日期:2007-06-01 00:00:00
abstract::In the course of studying the genetics of chlorambucil mutagenesis, we have uncovered a new model for autosomal polycystic kidney disease (PKD). In the homozygous condition, the gene, jcpk, causes a very severe disease characterized by cysts in all segments of the nephron. Death usually occurs before 10 days of age. E...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.69
更新日期:1995-02-01 00:00:00
abstract::The binding of albumin to the glomerular capillary wall was studied using albumin-gold in perfused kidneys, the interaction of [3H]albumin with isolated glomeruli at 37 degrees C and 4 degrees C and the interaction at [3H]albumin with purified basement membrane. The albumin-gold was found to bind predominantly to the ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.149
更新日期:1995-04-01 00:00:00
abstract::LECT2 amyloidosis is the latest systemic type of amyloidosis to be described. It was discovered in patients with nephrotic syndrome and renal failure and is characterized by amyloid deposition in glomeruli, renal vessels, and interstitium. Clinical and pathological features of earlier phases of this type of amyloidosi...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2010.18
更新日期:2010-05-01 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::Defective recycling of megalin consequent to impaired phosphatidylinositol metabolism has been implicated as a mechanism causing tubular proteinuria in patients with Lowe syndrome. In this issue, Berquez et al. describe an innovative approach using a clinically approved drug to "rebalance" phosphatidylinositols and re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.06.018
更新日期:2020-10-01 00:00:00
abstract::Pain was surveyed via structured interview and the McGill Pain Questionnaire in 53 dialysis and 27 transplant patients. Increased patient control over the dialysis procedure was not associated with a reduction in pain though perceived control may have been. Compliance with the dialysis regimen did not predict pain and...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1982.108
更新日期:1982-06-01 00:00:00
abstract:BACKGROUND:Endothelium-derived nitric oxide and reactive oxygen species (ROS) have been proposed to regulate vascular tone by complex mechanisms, including the modulation of ion channel function. In endothelial function itself, activation of Ca2+-activated K+ channels (KCa) plays a crucial role by inducing hyperpolariz...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00051.x
更新日期:2003-07-01 00:00:00
abstract::Neutrophil (PMN) recruitment into the peritoneum during acute bacterial peritonitis is an important part of the host defense barrier in CAPD patients. However, the subsequent phagocytosis of bacteria may also lead to PMN degranulation and the release of lysosomal enzymes. We determined the concentration of neutrophil ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.216
更新日期:1993-07-01 00:00:00
abstract:BACKGROUND:Bicarbonate reabsorption in the kidney proximal tubule is predominantly mediated via the apical Na+/H+ exchanger (NHE-3) and basolateral Na+: HCO(-3) cotransporter (NBC-1). The purpose of these studies was to examine the effects of Na+ load and altered acid-base status on the expression of NHE-3 and NBC-1 in...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00995.x
更新日期:2001-11-01 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::In his hypothesis of the evolution of renal functions Homer Smith proposed that the formation of glomerular nephron and body armor had been adequate for the appearance of primitive vertebrates in fresh water and that the adaptation of homoiotherms to terrestrial life was accompanied by the appearance of the loop of He...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1996.220
更新日期:1996-06-01 00:00:00
abstract:BACKGROUND:Although several kinds of evidence suggest that glycosaminoglycans (GAGs) and proteoglycans (PGs) may contribute to the development of beta2-microglobulin-related (Abeta2m) amyloidosis, the precise roles of these molecules for the development of Abeta2m amyloidosis are poorly understood. METHODS:We investig...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00167.x
更新日期:2003-09-01 00:00:00
abstract::Nitric oxide is generated from L-arginine by nitric oxide synthase (NOS), an enzyme that exists in several isoforms. Some studies found that a polymorphism (G894T) in the endothelial NOS gene was associated with decreased nitric oxide bioactivity and vascular complications. However, it is not known whether the enzyme ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.574
更新日期:2009-02-01 00:00:00
abstract::The present study was undertaken to evaluate some pathophysiological mechanisms of edema formation in diabetic nephropathy. Sixty-three subjects were investigated: 9 normal subjects (I), 9 normoalbuminuric Type 1 (insulin-dependent) diabetic patients (II), 15 microalbuminuric Type 1 diabetic patients (III), 16 Type 1 ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.332
更新日期:1990-12-01 00:00:00
abstract::The hypertrophy of renal proximal tubular cells occurs as an adaptive response to a variety of stimuli and may be involved with the progression of renal disease. Angiotensin II acting alone or in combination with other growth factors has been implicated in this process. The aims of this study were to identify the role...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.385
更新日期:1997-09-01 00:00:00
abstract::Hyperhomocysteinemia, an arteriosclerotic risk factor, persists in 75% of dialysis patients despite routine low dose supplementation with the B-vitamin co-factors/substrates for homocysteine (Hcy) metabolism, and normal or supernormal plasma status of these vitamins (Atherosclerosis 114:93, 1995). We conducted a place...
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:10.1038/ki.1996.19
更新日期:1996-01-01 00:00:00
abstract::For reasons that are not well understood, Aboriginal people with end-stage renal disease (ESRD) have lower rates of kidney transplantation. We hypothesized that distance between residence location and the closest transplant center was greater in Aboriginal dialysis patients and would partially explain the lower rate o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001607
更新日期:2006-09-01 00:00:00
abstract::In summary, it is evident that malnutrition is highly prevalent in ESRD patients. This is clearly related to multiple factors encountered during the pre-dialysis stage, as well as during maintenance dialysis therapy. A body of evidence highlights the existence of relationship between malnutrition and outcome in this p...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1996.323
更新日期:1996-08-01 00:00:00
abstract::In this issue, McMahon et al. report that, by combining phenotypic, metabolomic, and genetic data, they could better detect chronic kidney disease at the early stages and provide insight into its pathobiology. The most significant findings of the study are that several urinary metabolites (e.g., glycine and histidine)...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2017.03.022
更新日期:2017-06-01 00:00:00
abstract::Studies were performed in anesthetized dogs (N = 7) to determine the effects of synthetic atrial natriuretic peptide (ANP) on sodium excretion in the presence and absence of control of glomerular filtration rate produced by suprarenal aortic clamping. Intrarenal infusion of synthetic atrial natriuretic peptide (0.3 mi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.144
更新日期:1986-07-01 00:00:00
abstract::Eight patients with chronic renal failure (GFR 18.8 +/- 2.7 ml/min) were randomized to a crossover comparison of a very low protein diet (VLPD) containing 0.28 g protein and 35 kcal per kg per day, plus an isosmolar mixture of either ketoacids (KA) or essential amino acids (EAA). Subjects initiated the diets 14 days b...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1994.157
更新日期:1994-04-01 00:00:00