Mesangial cell biology

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Abboud, Hanna E., E-mail: Abboud@uthscsa.edu

2012-05-15

Mesangial cells originate from the metanephric mesenchyme and maintain structural integrity of the glomerular microvascular bed and mesangial matrix homeostasis. In response to metabolic, immunologic or hemodynamic injury, these cells undergo apoptosis or acquire an activated phenotype and undergo hypertrophy, proliferation with excessive production of matrix proteins, growth factors, chemokines and cytokines. These soluble factors exert autocrine and paracrine effects on the cells or on other glomerular cells, respectively. MCs are primary targets of immune-mediated glomerular diseases such as IGA nephropathy or metabolic diseases such as diabetes. MCs may also respond to injury that primarily involves podocytes and endothelial cells or to structural and genetic abnormalities of the glomerular basement membrane. Signal transduction and oxidant stress pathways are activated in MCs and likely represent integrated input from multiple mediators. Such responses are convenient targets for therapeutic intervention. Studies in cultured MCs should be supplemented with in vivo studies as well as examination of freshly isolated cells from normal and diseases glomeruli. In addition to ex vivo morphologic studies in kidney cortex, cells should be studied in their natural environment, isolated glomeruli or even tissue slices. Identification of a specific marker of MCs should help genetic manipulation as well as selective therapeutic targeting of these cells. Identification of biological responses of MCs that are not mediated by the renin–angiotensin system should help development of novel and effective therapeutic strategies to treat diseases characterized by MC pathology.

Mesangial cell biology

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Abboud, Hanna E.

2012-01-01

Mesangial cells originate from the metanephric mesenchyme and maintain structural integrity of the glomerular microvascular bed and mesangial matrix homeostasis. In response to metabolic, immunologic or hemodynamic injury, these cells undergo apoptosis or acquire an activated phenotype and undergo hypertrophy, proliferation with excessive production of matrix proteins, growth factors, chemokines and cytokines. These soluble factors exert autocrine and paracrine effects on the cells or on other glomerular cells, respectively. MCs are primary targets of immune-mediated glomerular diseases such as IGA nephropathy or metabolic diseases such as diabetes. MCs may also respond to injury that primarily involves podocytes and endothelial cells or to structural and genetic abnormalities of the glomerular basement membrane. Signal transduction and oxidant stress pathways are activated in MCs and likely represent integrated input from multiple mediators. Such responses are convenient targets for therapeutic intervention. Studies in cultured MCs should be supplemented with in vivo studies as well as examination of freshly isolated cells from normal and diseases glomeruli. In addition to ex vivo morphologic studies in kidney cortex, cells should be studied in their natural environment, isolated glomeruli or even tissue slices. Identification of a specific marker of MCs should help genetic manipulation as well as selective therapeutic targeting of these cells. Identification of biological responses of MCs that are not mediated by the renin–angiotensin system should help development of novel and effective therapeutic strategies to treat diseases characterized by MC pathology.

AS101 prevents diabetic nephropathy progression and mesangial cell dysfunction: regulation of the AKT downstream pathway.

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Itay Israel Shemesh

Full Text Available Diabetic nephropathy (DN is characterized by proliferation of mesangial cells, mesangial expansion, hypertrophy and extracellular matrix accumulation. Previous data have cross-linked PKB (AKT to TGFβ induced matrix modulation. The non-toxic compound AS101 has been previously shown to favorably affect renal pathology in various animal models and inhibits AKT activity in leukemic cells. Here, we studied the pharmacological properties of AS101 against the progression of rat DN and high glucose-induced mesangial dysfunction. In-vivo administration of AS101 to Streptozotocin injected rats didn't decreased blood glucose levels but ameliorated kidney hypotrophy, proteinuria and albuminuria and downregulated cortical kidney phosphorylation of AKT, GSK3β and SMAD3. AS101 treatment of primary rat glomerular mesangial cells treated with high glucose significantly reduced their elevated proliferative ability, as assessed by XTT assay and cell cycle analysis. This reduction was associated with decreased levels of p-AKT, increased levels of PTEN and decreased p-GSK3β and p-FoxO3a expression. Pharmacological inhibition of PI3K, mTORC1 and SMAD3 decreased HG-induced collagen accumulation, while inhibition of GSK3β did not affect its elevated levels. AS101 also prevented HG-induced cell growth correlated to mTOR and (rpS6 de-phosphorylation. Thus, pharmacological inhibition of the AKT downstream pathway by AS101 has clinical potential in alleviating the progression of diabetic nephropathy.

Lipid rafts are required for signal transduction by angiotensin II receptor type 1 in neonatal glomerular mesangial cells

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Adebiyi, Adebowale, E-mail: aadebiyi@uthsc.edu; Soni, Hitesh; John, Theresa A.; Yang, Fen

2014-05-15

Angiotensin II (ANG-II) receptors (AGTRs) contribute to renal physiology and pathophysiology, but the underlying mechanisms that regulate AGTR function in glomerular mesangium are poorly understood. Here, we show that AGTR1 is the functional AGTR subtype expressed in neonatal pig glomerular mesangial cells (GMCs). Cyclodextrin (CDX)-mediated cholesterol depletion attenuated cell surface AGTR1 protein expression and ANG-II-induced intracellular Ca{sup 2+} ([Ca{sup 2+}]{sub i}) elevation in the cells. The COOH-terminus of porcine AGTR1 contains a caveolin (CAV)-binding motif. However, neonatal GMCs express CAV-1, but not CAV-2 and CAV-3. Colocalization and in situ proximity ligation assay detected an association between endogenous AGTR1 and CAV-1 in the cells. A synthetic peptide corresponding to the CAV-1 scaffolding domain (CSD) sequence also reduced ANG-II-induced [Ca{sup 2+}]{sub i} elevation in the cells. Real-time imaging of cell growth revealed that ANG-II stimulates neonatal GMC proliferation. ANG-II-induced GMC growth was attenuated by EMD 66684, an AGTR1 antagonist; BAPTA, a [Ca{sup 2+}]{sub i} chelator; KN-93, a Ca{sup 2+}/calmodulin-dependent protein kinase II inhibitor; CDX; and a CSD peptide, but not PD 123319, a selective AGTR2 antagonist. Collectively, our data demonstrate [Ca{sup 2+}]{sub i}-dependent proliferative effect of ANG-II and highlight a critical role for lipid raft microdomains in AGTR1-mediated signal transduction in neonatal GMCs. - Highlights: • AGTR1 is the functional AGTR subtype expressed in neonatal mesangial cells. • Endogenous AGTR1 associates with CAV-1 in neonatal mesangial cells. • Lipid raft disruption attenuates cell surface AGTR1 protein expression. • Lipid raft disruption reduces ANG-II-induced [Ca{sup 2+}]{sub i} elevation in neonatal mesangial cells. • Lipid raft disruption inhibits ANG-II-induced neonatal mesangial cell growth.

Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis.

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Alcendor, Donald J

2017-07-15

Zika virus (ZIKV) infection in the human renal compartment has not been reported. Several clinical reports have describe high-level persistent viral shedding in the urine of infected patients, but the associated mechanisms have not been explored until now. The current study examined cellular components of the glomerulus of the human kidney for ZIKV infectivity. I infected primary human podocytes, renal glomerular endothelial cells (GECs), and mesangial cells with ZIKV. Viral infectivity was analyzed by means of microscopy, immunofluorescence, real-time reverse-transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR (qRT-PCR), and the proinflammatory cytokines interleukin 1β, interferon β, and RANTES (regulated on activation of normal T cells expressed and secreted) were assessed using qRT-PCR. I show that glomerular podocytes, renal GECs, and mesangial cells are permissive for ZIKV infection. ZIKV infectivity was confirmed in all 3 cell types by means of immunofluorescence staining, RT-PCR, and qRT-PCR, and qRT-PCR analysis revealed increased transcriptional induction of interleukin 1β, interferon β, and RANTES in ZIKV-infected podocytes at 72 hours, compared with renal GECs and mesangial cells. The findings of this study support the notion that the glomerulus may serve as an amplification reservoir for ZIKV in the renal compartment. The impact of ZIKV infection in the human renal compartment is unknown and will require further study. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

The transcription factor ETS-1 regulates angiotensin II-stimulated fibronectin production in mesangial cells.

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Hua, Ping; Feng, Wenguang; Rezonzew, Gabriel; Chumley, Phillip; Jaimes, Edgar A

2012-06-01

Angiotensin II (ANG II) produced as result of activation of the renin-angiotensin system (RAS) plays a critical role in the pathogenesis of chronic kidney disease via its hemodynamic effects on the renal microcirculation as well as by its nonhemodynamic actions including the production of extracellular matrix proteins such as fibronectin, a multifunctional extracellular matrix protein that plays a major role in cell adhesion and migration as well as in the development of glomerulosclerosis. ETS-1 is an important transcription factor essential for normal kidney development and glomerular integrity. We previously showed that ANG II increases ETS-1 expression and is required for fibronectin production in mesangial cells. In these studies, we determined that ANG II induces phosphorylation of ETS-1 via activation of the type 1 ANG II receptor and that Erk1/2 and Akt/PKB phosphorylation are required for these effects. In addition, we characterized the role of ETS-1 on the transcriptional activation of fibronectin production in mesangial cells. We determined that ETS-1 directly activates the fibronectin promoter and by utilizing gel shift assays and chromatin immunoprecipitation assays identified two different ETS-1 binding sites that promote the transcriptional activation of fibronectin in response to ANG II. In addition, we identified the essential role of CREB and its coactivator p300 on the transcriptional activation of fibronectin by ETS-1. These studies unveil novel mechanisms involved in RAS-induced production of the extracellular matrix protein fibronectin in mesangial cells and establish the role of the transcription factor ETS-1 as a direct mediator of these effects.

Acute renal failure due to mesangial proliferative glomerulonephritis in a pregnant woman with primary Sjögren's syndrome.

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Adam, Fatma Ulku; Torun, Dilek; Bolat, Filiz; Zumrutdal, Aysegul; Sezer, Siren; Ozdemir, Fatma Nurhan

2006-02-01

The most common form of renal involvement in Sjögren's syndrome (SS) is tubulointerstitial nephritis. Renal dysfunction is usually mild and subclinical. Glomerulonephritis (GMN) is rare in patients with SS. We report a 28-year-old multigravida patient with primary Sjögren's syndrome (pSS) and associated manifestations, who presented with acute renal failure in the 20th week of her fifth pregnancy. The complaints and clinical findings, positive Schirmer's test, findings of dry eye on ophthalmologic examination, and the salivary gland biopsy were compatible with SS. The patient exhibited no other clinical or laboratory findings indicative of other collagenous disease and/or rheumatoid arthritis. She refused renal biopsy, hesitating for fear of fetal loss; thus, based on the clinical and laboratory findings indicating rapidly progressive GMN and vasculitis, prednisolone, plasmapheresis, and one dose of cyclophosphamide were administered during the pregnancy. Hemodialysis five times weekly was performed. At the 28th week of gestation, she underwent a cesarean section due to early rupture of membranes and fetal distress. A healthy male boy was delivered. The renal biopsy performed 2 weeks after labor revealed mesangial proliferative glomerulonephritis. After the fourth cyclophosphamide treatment, her urinary output increased and she was discharged from the hemodialysis program. She remains in follow-up at our outpatient clinic free of hemodialysis for 4 months. This is the first report of mesangial proliferative GMN requiring dialysis in a pregnant pSS patient that has featured good maternal and fetal outcomes.

NG2 proteoglycan increases mesangial cell proliferation and extracellular matrix production

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Xiong Jing; Wang Yang; Zhu, Zhonghua; Liu Jianshe; Wang Yumei; Zhang Chun; Hammes, Hans-Peter; Lang, Florian; Feng Yuxi

2007-01-01

As a membrane-spanning protein, NG2 chondroitin sulfate proteoglycan interacts with molecules on both sides of plasma membrane. The present study explored the role of NG2 in the pathogenesis of diabetic nephropathy. In the normal kidneys, NG2 was observed predominantly in glomerular mesangium, Bowman's capsule and interstitial vessels. Both mRNA and protein expression in kidneys was significantly higher in strepozotocin-induced diabetic rats than that in normal rats. In the cultured rat mesangial cell line HBZY-1, overexpression of NG2 promoted mesangial cell proliferation and extracellular matrix (ECM) production, such as type VI collagen and laminin. Furthermore, target knockdown of NG2 resulted in decreased cell proliferation and ECM formation. The observations suggest that NG2 is up-regulated in diabetic nephropathy. It actively participates in the development and progression of glomerulosclerosis by stimulating proliferation of mesangial cells and deposition of ECM

Synthesis of alkyl-ether glycerophospholipids in rat glomerular mesangial cells: evidence for alkyldihydroxyacetone phosphate synthase activity

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Zanglis, A.; Lianos, E.A.

1987-01-01

We studied the ability of rat glomerular mesangial cells and their microsomal fractions to incorporate 1-[ 14 C]hexadecanol to glycerophospholipids via an O-alkyl ether linkage and assessed the presence and activity of the required enzyme: alkyl-dihydroxy acetone phosphate synthase. Suspensions of cultured mesangial cells incorporated 1-[ 14 C]hexadecanol to the phosphatidyl ethanolamine and phosphatidyl choline lipid pools, via a bond resistant to acid and base hydrolysis. When cell homogenates or microsomal fractions were incubated with palmitoyl-DHAP and 1-[ 14 C]hexadecanol, alkyl-DHAP and 1-O-alkyl glycerol were formed (alkyl:hexadecyl). The activity of the enzyme responsible for the O-alkyl product formation was calculated to be 2.5 +/- 0.3 and 544 +/- 50 pmoles/min/mg protein for mesangial cell homogenates and mesangial cell microsomes, respectively. These observations provide evidence that mesangial cells may elaborate either linked lipid precursors de novo for the biosynthesis of O-alkyl glycerophospholipids

Resveratrol inhibits the intracellular calcium increase and angiotensin/endothelin system activation induced by soluble uric acid in mesangial cells

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Albertoni, G.; Schor, N. [Divisão de Nefrologia, Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

2014-10-24

Resveratrol (Resv) is natural polyphenol found in grapes. This study evaluated the protective effect of Resv against the effects of uric acid (UA) in immortalized human mesangial cells (ihMCs). ihMCs were preincubated with Resv (12.5 µM) for 1 h and treated with UA (10 mg/dL) for 6 or 12 h. The intracellular calcium concentration [Ca{sup 2+}]i was quantified by fluorescence using flow cytometry. Angiotensinogen (AGT) and pre-pro endothelin-1 (ppET-1) mRNA were assayed by quantitative real-time RT-PCR. Angiotensin II (AII) and endothelin-1 (ET-1) were assayed by ELISA. UA significantly increased [Ca{sup 2+}]i. Pre-incubation with Resv significantly reduced the change in [Ca{sup 2+}]i induced by UA. Incubation with UA for 6 or 12 h also increased AGT mRNA expression and AII protein synthesis. Resv blunted these increases in AGT mRNA expression and AII protein. Incubation with UA in the ihMCs increased ppET-1 expression and ET-1 protein synthesis at 6 and 12 h. When ihMCs were pre-incubated with Resv, UA had a significantly diminished effect on ppET-1 mRNA expression and ET-1 protein synthesis at 6 and 12 h, respectively. Our results suggested that UA triggers reactions including AII and ET-1 production in mesangial cells. The renin-angiotensin system may contribute to the pathogenesis of renal function and chronic kidney disease. Resv can minimize the impact of UA on AII, ET-1 and the increase of [Ca{sup 2+}]i in mesangial cells, suggesting that, at least in part, Resv can prevent the effects of soluble UA in mesangial cells.

Nuclear hormone receptor expression in mouse kidney and renal cell lines.

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Daisuke Ogawa

Full Text Available Nuclear hormone receptors (NHRs are transcription factors that regulate carbohydrate and lipid metabolism, immune responses, and inflammation. Although several NHRs, including peroxisome proliferator-activated receptor-γ (PPARγ and PPARα, demonstrate a renoprotective effect in the context of diabetic nephropathy (DN, the expression and role of other NHRs in the kidney are still unrecognized. To investigate potential roles of NHRs in the biology of the kidney, we used quantitative real-time polymerase chain reaction to profile the expression of all 49 members of the mouse NHR superfamily in mouse kidney tissue (C57BL/6 and db/m, and cell lines of mesangial (MES13, podocyte (MPC, proximal tubular epithelial (mProx24 and collecting duct (mIMCD3 origins in both normal and high-glucose conditions. In C57BL/6 mouse kidney cells, hepatocyte nuclear factor 4α, chicken ovalbumin upstream promoter transcription factor II (COUP-TFII and COUP-TFIII were highly expressed. During hyperglycemia, the expression of the NHR 4A subgroup including neuron-derived clone 77 (Nur77, nuclear receptor-related factor 1, and neuron-derived orphan receptor 1 significantly increased in diabetic C57BL/6 and db/db mice. In renal cell lines, PPARδ was highly expressed in mesangial and proximal tubular epithelial cells, while COUP-TFs were highly expressed in podocytes, proximal tubular epithelial cells, and collecting duct cells. High-glucose conditions increased the expression of Nur77 in mesangial and collecting duct cells, and liver x receptor α in podocytes. These data demonstrate NHR expression in mouse kidney cells and cultured renal cell lines and suggest potential therapeutic targets in the kidney for the treatment of DN.

A Proteomic Screen Identified Stress-Induced Chaperone Proteins as Targets of Akt Phosphorylation in Mesangial Cells

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Barati, Michelle T.; Rane, Madhavi J.; Klein, Jon B.; McLeish, Kenneth R.

2006-01-01

The serine-threonine kinase Akt regulates mesangial cell apoptosis, proliferation, and hypertrophy. To define Akt signaling pathways in mesangial cells, we performed a functional proteomic screen for rat mesangial cell proteins phosphorylated by Akt. A group of chaperone proteins, heat shock protein (Hsp) 70, Hsp90α, Hsp90β, Glucose-regulated protein (Grp) Grp78, Grp94, and protein disulfide isomerase (PDI) were identified as potential Akt substrates by two techniques: (a) in vitro phosphoryl...

High Glucose-Induced Oxidative Stress Increases the Copy Number of Mitochondrial DNA in Human Mesangial Cells

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Ghada Al-Kafaji

2013-01-01

Full Text Available Oxidative damage to mitochondrial DNA (mtDNA has been linked to the pathogenicity of diabetic nephropathy. We tested the hypothesis that mtDNA copy number may be increased in human mesangial cells in response to high glucose-induced reactive oxygen species (ROS to compensate for damaged mtDNA. The effect of manganese superoxide dismutase mimetic (MnTBAP on glucose-induced mtDNA copy number was also examined. The copy number of mtDNA was determined by real-time PCR in human mesangial cells cultured in 5 mM glucose, 25 mM glucose, and mannitol (osmotic control, as well as in cells cultured in 25 mM glucose in the presence and absence of 200 μM MnTBAP. Intracellular ROS was assessed by confocal microscopy and flow cytometry in human mesangial cells. The copy number of mtDNA was significantly increased when human mesangial cells were incubated with 25 mM glucose compared to 5 mM glucose and mannitol. In addition, 25 mM glucose rapidly generated ROS in the cells, which was not detected in 5 mM glucose. Furthermore, mtDNA copy number was significantly decreased and maintained to normal following treatment of cells with 25 mM glucose and MnTBAP compared to 25 mM glucose alone. Inclusion of MnTBAP during 25 mM glucose incubation inhibited mitochondrial superoxide in human mesangial cells. Increased mtDNA copy number in human mesangial cells by high glucose could contribute to increased mitochondrial superoxide, and prevention of mtDNA copy number could have potential in retarding the development of diabetic nephropathy.

Klotho down-regulates Egr-1 by inhibiting TGF-β1/Smad3 signaling in high glucose treated human mesangial cells

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Li, Yang; Hu, Fang; Xue, Meng; Jia, Yi-Jie; Zheng, Zong-Ji; Wang, Ling; Guan, Mei-Ping; Xue, Yao-Ming

2017-01-01

Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease worldwide and is associated with glomerular mesangial cell (MC) proliferation and excessive extracellular matrix (ECM) production. Klotho can attenuate renal fibrosis in part by inhibiting TGF-β1/Smad3 signaling in DKD. Early growth response factor 1 (Egr-1) has been shown to play a key role in renal fibrosis in part by facilitating the formation of a positive feedback loop involving TGF-β1. However, whether Klotho down-regulates Egr-1 by inhibiting TGF-β1/Smad3 signaling in DKD is unclear. In the present study, we assessed human MCs that were incubated under high-glucose conditions to mimic diabetes. Then, we transfected the cells with Klotho plasmid or siRNA to overexpress or knock down Klotho gene and protein expression. Klotho, Egr-1, fibronectin (FN), collagen type I (Col I), Smad3 and phosphorylated Smad3 (p-Smad3) gene and protein expression levels were determined by RT-qPCR and western blotting respectively. High glucose time-dependently down-regulated Klotho mRNA and protein expression in cultured human MCs. pcDNA3.1-Klotho transfection-mediated Klotho overexpression down-regulated Egr-1, FN and Col I expression and the p-Smad3/Smad3 ratio in human MCs. Conversely, siRNA-mediated Klotho silencing up-regulated Egr-1, FN, and Col I expression and the p-Smad3/Smad3 ratio. Moreover, the effects of si-Klotho on Egr-1 expression were abolished by the TGF-β1 inhibitor SB-431542. Klotho overexpression can prevent mesangial ECM production in high-glucose-treated human MCs, an effect that has been partially attributed to Egr-1 down-regulation facilitated by TGF-β1/Smad3 signaling inhibition. - Highlights: • High glucose time-dependently down-regulated Klotho mRNA and protein expression in cultured human MCs. • Klotho overexpression down-regulated Egr-1 and prevented mesangial ECM production in high-glucose-treated human MCs. • Klotho down-regulated Egr-1 by inhibiting

Studies on binding and mitogenic effect of insulin and insulin-like growth factor I in glomerular mesangial cells

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Conti, F.G.; Striker, L.J.; Lesniak, M.A.; MacKay, K.; Roth, J.; Striker, G.E.

1988-01-01

The mesangial cells are actively involved in regulating glomerular hemodynamics. Their overlying endothelium is fenestrated; therefore, these cells are directly exposed to plasma substances, including hormones such as insulin and insulin-like growth factor I (IGF-I). These peptides may contribute to the mesangial sclerosis and cellular hyperplasia that characterize diabetic glomerulopathy. We report herein the characterization of the receptors and the mitogenic effects of IGF-I and insulin on mouse glomerular mesangial cells in culture. The IGF-I receptor was characterized on intact cells. The Kd of the IGF-I receptor was 1.47 X 10(-9) M, and the estimated number of sites was 64,000 receptors/cell. The binding was time, temperature, and pH dependent, and the receptor showed down-regulation after exposure to serum. The expression of the receptor did not change on cells at different densities. The specific binding for insulin was too low to allow characterization of the insulin receptor on intact cells. However, it was possible to identify the insulin receptor in a wheat germ agglutinin-purified preparation of solubilized mesangial cells. This receptor showed the characteristic features of the insulin receptor, including pH dependence of binding and a curvilinear Scatchard plot. The mitogenic effects of insulin and IGF-I on mesangial cells were measured by the incorporation of [3H]thymidine into DNA. IGF-I was more potent than insulin. The half-maximal response to IGF-I stimulation occurred at 1.3 X 10(-10) M, and a similar increase with insulin was observed at concentrations in the range of 10(-7) M, suggesting that this insulin action was mediated through the IGF-I receptor. These data show that the mouse microvascular smooth muscle cells of the glomerulus express a cell surface receptor for IGF-I in vitro and that this peptide is a potent mitogen for these mesangial cells

Glucose Stimulation of Transforming Growth Factor-β Bioactivity in Mesangial Cells Is Mediated by Thrombospondin-1

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Poczatek, Maria H.; Hugo, Christian; Darley-Usmar, Victor; Murphy-Ullrich, Joanne E.

2000-01-01

Glucose is a key factor in the development of diabetic complications, including diabetic nephropathy. The development of diabetic glomerulosclerosis is dependent on the fibrogenic growth factor, transforming growth factor-β (TGF-β). Previously we showed that thrombospondin-1 (TSP-1) activates latent TGF-β both in vitro and in vivo. Activation occurs as the result of specific interactions of latent TGF-β with TSP-1, which potentially alter the conformation of latent TGF-β. As glucose also up-regulates TSP-1 expression, we hypothesized that the increased TGF-β bioactivity observed in rat and human mesangial cells cultured with high glucose concentrations is the result of latent TGF-β activation by autocrine TSP-1. Glucose-induced bioactivity of TGF-β in mesangial cell cultures was reduced to basal levels by peptides from two different sequences that antagonize activation of latent TGF-β by TSP, but not by the plasmin inhibitor, aprotinin. Furthermore, glucose-dependent stimulation of matrix protein synthesis was inhibited by these antagonist peptides. These studies demonstrate that glucose stimulation of TGF-β activity and the resultant matrix protein synthesis are dependent on the action of autocrine TSP-1 to convert latent TGF-β to its biologically active form. These data suggest that antagonists of TSP-dependent TGF-β activation may be the basis of novel therapeutic approaches for ameliorating diabetic renal fibrosis. PMID:11021838

miR-184 and miR-150 promote renal glomerular mesangial cell aging by targeting Rab1a and Rab31.

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Liu, Xiujuan; Fu, Bo; Chen, Dapeng; Hong, Quan; Cui, Jing; Li, Jin; Bai, Xueyuan; Chen, Xiangmei

2015-08-15

The molecular mechanism of kidney aging is not well understood, but the abnormal expression of miRNAs with aging is considered to be an important contributor. miR-184 and miR-150 were screened using a miRNA microarray and qRT-PCR and found to be significantly upregulated in 24-month-old rats. Rat renal primary glomerular mesangial cells (GMCs) were isolated from 3-month and 24-month-old rats for the in vitro analysis of the roles of miR-184 and miR-150 in kidney aging. Bioinformatics analyses suggested that Rab1a and Rab31, which are associated with cell autophagy, were targeted by both miR-184 and miR-150. miR-184 and miR-150 were increased significantly in aging GMCs versus young cells, while Rab1a and Rab31 were significantly lower in aging cells. Furthermore, dual luciferase reporter assays revealed that miR-184 and miR-150 bound to the 3'-UTR of Rab1a and Rab31 mRNAs. Transfection of miR-184 and miR-150 mimics into young GMCs suppressed the expression of Rab1a and Rab31. Transfected cells showed lower autophagy activities and higher levels of cellular oxidative products, leading to the aging of young GMCs. However, miR-184 and miR-150 inhibitors promoted autophagy and reduced oxidative damage by upregulating Rab1a and Rab31 in old GMCs. In conclusion, miR-184 and miR-150 inhibited autophagy, promoting GMC aging. Copyright © 2015 Elsevier Inc. All rights reserved.

Response of Renal Podocytes to Excessive Hydrostatic Pressure: a Pathophysiologic Cascade in a Malignant Hypertension Model

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Ramzia Abu Hamad

2017-12-01

Full Text Available Background/Aims: Renal injuries induced by increased intra-glomerular pressure coincide with podocyte detachment from the glomerular basement membrane (GBM. In previous studies, it was demonstrated that mesangial cells have a crucial role in the pathogenesis of malignant hypertension. However, the exact pathophysiological cascade responsible for podocyte detachment and its relationship with mesangial cells has not been fully elucidated yet and this was the aim of the current study. Methods: Rat renal mesangial or podocytes were exposed to high hydrostatic pressure in an in-vitro model of malignant hypertension. The resulted effects on podocyte detachment, apoptosis and expression of podocin and integrinβ1 in addition to Angiotensin-II and TGF-β1 generation were evaluated. To simulate the paracrine effect podocytes were placed in mesangial cell media pre-exposed to pressure, or in media enriched with Angiotensin-II, TGF-β1 or receptor blockers. Results: High pressure resulted in increased Angiotensin-II levels in mesangial and podocyte cells. Angiotensin-II via the AT1 receptors reduced podocin expression and integrinβ1, culminating in detachment of both viable and apoptotic podocytes. Mesangial cells exposed to pressure had a greater increase in Angiotensin-II than pressure-exposed podocytes. The massively increased concentration of Angiotensin-II by mesangial cells, together with increased TGF-β1 production, resulted in increased apoptosis and detachment of non-viable apoptotic podocytes. Unlike the direct effect of pressure on podocytes, the mesangial mediated effects were not related to changes in adhesion proteins expression. Conclusions: Hypertension induces podocyte detachment by autocrine and paracrine effects. In a direct response to pressure, podocytes increase Angiotensin-II levels. This leads, via AT1 receptors, to structural changes in adhesion proteins, culminating in viable podocyte detachment. Paracrine effects of

Cell-type-specific activation of mitogen-activated protein kinases in PAN-induced progressive renal disease in rats

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Park, Sang-Joon; Jeong, Kyu-Shik

2004-01-01

We examined the time-course activation and the cell-type specific role of MAP kinases in puromycin aminonucleoside (PAN)-induced renal disease. The maximal activation of c-Jun-NH 2 -terminal kinase (JNK), extracellular signal regulated kinase (ERK), and p38 MAP kinase was detected on Days 52, 38, and 38 after PAN-treatment, respectively. p-JNK was localized in mesangial and proximal tubular cells at the early renal injury. It was expressed, therefore, in the inflammatory cells of tubulointerstitial lesions. While, p-ERK was markedly increased in the glomerular regions and macrophages p-p38 was observed in glomerular endothelial cells, tubular cells, and some inflammatory cells. The results show that the activation of MAP kinases in the early renal injury by PAN-treatment involves cellular changes such as cell proliferation or apoptosis in renal native cells. The activation of MAP kinases in infiltrated inflammatory cells and fibrotic cells plays an important role in destructive events such as glomerulosclerosis and tubulointerstitial fibrosis

Mapping of Carboxypeptidase M in Normal Human Kidney and Renal Cell Carcinoma

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Denis, Catherine J.; Van Acker, Nathalie; De Schepper, Stefanie; De Bie, Martine; Andries, Luc; Fransen, Erik; Hendriks, Dirk; Kockx, Mark M.

2013-01-01

Although the kidney generally has been regarded as an excellent source of carboxypeptidase M (CPM), little is known about its renal-specific expression level and distribution. This study provides a detailed localization of CPM in healthy and diseased human kidneys. The results indicate a broad distribution of CPM along the renal tubular structures in the healthy kidney. CPM was identified at the parietal epithelium beneath the Bowman’s basement membrane and in glomerular mesangial cells. Capillaries, podocytes, and most interstitial cells were CPM negative. Tumor cells of renal cell carcinoma subtypes lose CPM expression upon dedifferentiation. Tissue microarray analysis demonstrated a correlation between low CPM expression and tumor cell type. CPM staining was intense on phagocytotic tumor-associated macrophages. Immunoreactive CPM was also detected in the tumor-associated vasculature. The absence of CPM in normal renal blood vessels points toward a role for CPM in angiogenesis. Coexistence of CPM and the epidermal growth factor receptor (EGFR) was detected in papillary renal cell carcinoma. However, the different subcellular localization of CPM and EGFR argues against an interaction between these h proteins. The description of the distribution of CPM in human kidney forms the foundation for further study of the (patho)physiological activities of CPM in the kidney. PMID:23172796

Emodin attenuates high glucose-induced TGF-β1 and fibronectin expression in mesangial cells through inhibition of NF-κB pathway

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Yang, Jie; Zeng, Zhi; Wu, Teng; Yang, Zhicheng; Liu, Bing; Lan, Tian

2013-01-01

The activation of nuclear factor-κB (NF-κB) and the subsequent overexpression of its downstream targets transforming growth factor-β1 (TGF-β1) and fibronectin (FN) are among the hallmarks for the progressive diabetic nephropathy. Our previous studies demonstrated that emodin ameliorated renal injury and inhibited extracellular matrix accumulation in kidney and mesangial cells under diabetic condition. However, the molecular mechanism has not been fully elucidated. Here, we showed that emodin significantly attenuated high glucose-induced NF-κB nuclear translocation in mesangial cells. Interestingly, emodin also inhibited the DNA-binding activity and transcriptional activity of NF-κB. Furthermore, NF-κB-mediated TGF-β1 and FN expression was significantly decreased by emodin. These results demonstrated that emodin suppressed TGF-β1 and FN overexpression through inhibition of NF-κB activation, suggesting that emodin-mediated inhibition of the NF-κB pathway could protect against diabetic nephropathy. - Highlights: • Emodin decreased high glucose-induced p65 phosphorylation in MCs. • Emodin decreased high glucose-induced IκB-α degradation in MCs. • Emodin decreased high glucose-induced p65 translocation in MCs. • Emodin blocked high glucose-induced NF-κB activity. • Emodin blocked high glucose-induced the expression of TGF-β1 and FN

6-Hydroxyflavone and derivatives exhibit potent anti-inflammatory activity among mono-, di- and polyhydroxylated flavones in kidney mesangial cells.

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Xing Wang

Full Text Available Inflammatory responses by kidney mesangial cells play a critical role in the glomerulonephritis. The anti-inflammatory potential of nineteen mono-, di- and polyhydroxylated flavones including fisetin, quercetin, morin, tricetin, gossypetin, apigenin and myricetin were investigated on rat mesangial cells with lipopolysaccharide (LPS as the inflammatory stimuli. 6-Hydroxyflavone and 4',6-dihydroxyflavone exhibited high activity with IC50 in the range of 2.0 μM, a much better inhibition potential in comparison to the well-studied polyhydroxylated flavones. Interestingly, the anti-inflammatory activity was not due to direct quenching of NO radicals. Investigation on derivatives with methylation, acetylation or sulfation of 6-hydroxyl group revealed that 6-methoxyflavone was the most potent with an IC50 of 192 nM. Mechanistic study indicated that the anti-inflammatory activity of 6-methoxyflavone arose via the inhibition of LPS-induced downstream inducible NO synthase in mesangial cells. The identification of 6-hydroxyflavone and 6-methoxyflavone with potent anti-inflammatory activity in kidney mesangial cells provides a new flavone scaffold and direction to develop naturally derived products for potential nephritis prevention and treatment.

[Wnt/β-catenin pathway involved in the regulation of rat mesangial cell proliferation by adipose-derived mesenchymal stem cells].

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Li, Zhi; Zhang, Mengying; Li, Xueqin; Lu, Jinming; Xu, Liang

2016-11-01

Objective To investigate the effect of adipose-derived mesenchymal stem cells (ADSCs) on glomerular mesangial cell proliferation via Wnt/β-catenin pathway. Methods The rat glomerular mesangial cells (HBZY-1) were incubated in conditioned ADSC medium. Cell cycle was analyzed with flow cytometry; the proliferation rate of HBZY-1 and the expression levels of relative genes and proteins of Wnt signaling pathway were measured using RNA interference, quantitative real-time PCR and Western blotting, respectively. Results HBZY-1 proliferation was significantly inhibited under the action of conditioned ADSC medium, whereas dickkopf WNT signaling pathway inhibitor 1 (DKK1) mRNA level was up-regulated. Fibronectin and TGF-β1 mRNA expression as well as β-catenin and Bcl-2 protein levels of HBZY-1 were significantly down-regulated. DKK1 gene expression level in ADSCs was significantly higher than that of HBZY-1. After RNA interference, DKK1 expression level in ADSCs was markedly inhibited, yet the β-catenin protein level was notably elevated. The β-catenin and Bcl-2 protein levels of HBZY-1 were also significantly raised in HBZY-1 after cultured with conditioned medium containing ADSCs treated with RNA interference. Conclusion Wnt/β-catenin may be a potential signaling pathway involved in the regulative effect of ADSCs on glomerular mesangial cell proliferation.

Involvement of Histone Lysine Methylation in p21 Gene Expression in Rat Kidney In Vivo and Rat Mesangial Cells In Vitro under Diabetic Conditions

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Xiangjun Li

2016-01-01

Full Text Available Diabetic nephropathy (DN, a common complication associated with type 1 and type 2 diabetes mellitus (DM, characterized by glomerular mesangial expansion, inflammation, accumulation of extracellular matrix (ECM protein, and hypertrophy, is the major cause of end-stage renal disease (ESRD. Increasing evidence suggested that p21-dependent glomerular and mesangial cell (MC hypertrophy play key roles in the pathogenesis of DN. Recently, posttranscriptional modifications (PTMs have uncovered novel molecular mechanisms involved in DN. However, precise regulatory mechanism of histone lysine methylation (HKme mediating p21 related hypertrophy associated with DN is not clear. We evaluated the roles of HKme and histone methyltransferase (HMT SET7/9 in p21 gene expression in glomeruli of diabetic rats and in high glucose- (HG- treated rat mesangial cells (RMCs. p21 gene expression was upregulated in diabetic rats glomeruli; chromatin immunoprecipitation (ChIP assays showed decreased histone H3-lysine9-dimethylation (H3K9me2 accompanied with enhanced histone H3-lysine4-methylation (H3K4me1/3 and SET7/9 occupancies at the p21 promoter. HG-treated RMCs exhibited increased p21 mRNA, H3K4me level, SET7/9 recruitment, and inverse H3K9me, which were reversed by TGF-β1 antibody. These data uncovered key roles of H3Kme and SET7/9 responsible for p21 gene expression in vivo and in vitro under diabetic conditions and confirmed preventive effect of TGF-β1 antibody on DN.

Expression and mechanism of mammalian target of rapamycin in age-related renal cell senescence and organ aging.

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Zhuo, Li; Cai, Guangyan; Liu, Fuyou; Fu, Bo; Liu, Weiping; Hong, Quan; Ma, Qiang; Peng, Youming; Wang, Jianzhong; Chen, Xiangmei

2009-10-01

The mammalian target of rapamycin (mTOR) is relevant to cell senescence and organismal aging. This study firstly showed that the level of mTOR expression increased with aging in rat kidneys, rat mesangial cells and WI-38 cells (P aging-related phenotypes were all reduced in cells treated with rapamycin (an inhibitor of mTOR) than in control cells (P aging, and that mTOR may promote cellular senescence by regulating the cell cycle through p21(WAF1/CIP1/SDI1), which might provide a new target for preventing renal aging.

[Could isolated mesangial deposits of C3 be responsible of glomerular hematuric nephropathies (author's transl)].

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Saint-Andre, J P; Touzard, D; Houssin, A; Simard, C

1982-01-01

This communication presents three cases of prolonged macroscopic hematuria in young subjects. Complementary explorations eliminated urologic or vascular causes. Renal biopsies showed minimal glomerular lesions with light microscopy, normal basement membranes in electron microscopy and mesangial deposits of C3 and properdine in immunofluorescence. Although the mesangial deposits of C3 lack specificity and the number of observations is small, it appears useful to report such cases so as to indicate their frequency and perhaps their autonomy, in glomerular hematuric nephropathies.

Resveratrol protects against hyperglycemia-induced oxidative damage to mitochondria by activating SIRT1 in rat mesangial cells

International Nuclear Information System (INIS)

Xu, Ying; Nie, Ling; Yin, Yang-Guang; Tang, Jian-Lin; Zhou, Ji-Yin; Li, Dan-Dan; Zhou, Shi-Wen

2012-01-01

Oxidative stress and mitochondrial dysfunction are involved in the pathogenesis of diabetic nephropathy (DN). Resveratrol has potent protective effects on diabetes and diabetic complications including diabetic nephropathy. We aimed to investigate the protective effects of resveratrol on mitochondria and the underlying mechanisms by using an in vitro model of hyperglycemia. We exposed primary cultured rat mesangial cells to high glucose (30 mM) for 48 h. We found that pretreatment with resveratrol (10 μM) 6 h prior to high glucose treatment significantly reduced hyperglycemia-induced increase in reactive oxygen species (ROS) production and mitochondrial superoxide generation, as well as stimulated MnSOD activity. In addition, resveratrol pretreatment significantly reversed the decrease of mitochondrial complex III activity in glucose-treated mesangial cells, which is considered to be the major source of mitochondrial oxidative stress in glucose-treated cells. Furthermore, resveratrol pretreatment efficiently restored the hyperpolarization of ∆Ψm, increased ATP production and preserved the mtDNA content. All of these protective effects of resveratrol were successfully blocked by siRNA targeting SIRT1 and EX-527, a specific inhibitor of SIRT1 activity. Our results indicated that resveratrol efficiently reduced oxidative stress and maintained mitochondrial function related with activating SIRT1 in glucose-treated mesangial cells. It suggested that resveratrol is pharmacologically promising for treating diabetic nephropathy. -- Highlights: ► We treat mesangial cells with glucose as an in vitro model of diabetic nephropathy. ► We find that the nephroprotective effects of resveratrol relate with mitochondria. ► The beneficial effect of resveratrol was prevented by siRNA SIRT1 or its inhibitor.

Resveratrol protects against hyperglycemia-induced oxidative damage to mitochondria by activating SIRT1 in rat mesangial cells

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Xu, Ying [Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Nie, Ling [Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Yin, Yang-Guang [Emergency Department, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Tang, Jian-Lin; Zhou, Ji-Yin; Li, Dan-Dan [Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Zhou, Shi-Wen, E-mail: Zhoushiwen1956@yahoo.cn [Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China)

2012-03-15

Oxidative stress and mitochondrial dysfunction are involved in the pathogenesis of diabetic nephropathy (DN). Resveratrol has potent protective effects on diabetes and diabetic complications including diabetic nephropathy. We aimed to investigate the protective effects of resveratrol on mitochondria and the underlying mechanisms by using an in vitro model of hyperglycemia. We exposed primary cultured rat mesangial cells to high glucose (30 mM) for 48 h. We found that pretreatment with resveratrol (10 μM) 6 h prior to high glucose treatment significantly reduced hyperglycemia-induced increase in reactive oxygen species (ROS) production and mitochondrial superoxide generation, as well as stimulated MnSOD activity. In addition, resveratrol pretreatment significantly reversed the decrease of mitochondrial complex III activity in glucose-treated mesangial cells, which is considered to be the major source of mitochondrial oxidative stress in glucose-treated cells. Furthermore, resveratrol pretreatment efficiently restored the hyperpolarization of ∆Ψm, increased ATP production and preserved the mtDNA content. All of these protective effects of resveratrol were successfully blocked by siRNA targeting SIRT1 and EX-527, a specific inhibitor of SIRT1 activity. Our results indicated that resveratrol efficiently reduced oxidative stress and maintained mitochondrial function related with activating SIRT1 in glucose-treated mesangial cells. It suggested that resveratrol is pharmacologically promising for treating diabetic nephropathy. -- Highlights: ► We treat mesangial cells with glucose as an in vitro model of diabetic nephropathy. ► We find that the nephroprotective effects of resveratrol relate with mitochondria. ► The beneficial effect of resveratrol was prevented by siRNA SIRT1 or its inhibitor.

Andrographolide ameliorates diabetic nephropathy by attenuating hyperglycemia-mediated renal oxidative stress and inflammation via Akt/NF-κB pathway.

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Ji, Xiaoqian; Li, Changzheng; Ou, Yitao; Li, Ning; Yuan, Kai; Yang, Guizhi; Chen, Xiaoyan; Yang, Zhicheng; Liu, Bing; Cheung, Wai W; Wang, Lijing; Huang, Ren; Lan, Tian

2016-12-05

Diabetic nephropathy (DN) is characterized by proliferation of mesangial cells, mesangial hypertrophy and extracellular matrix (ECM) accumulation. Our recent study found that andrographolide inhibited high glucose-induced mesangial cell proliferation and fibronectin expression through inhibition of AP-1 pathway. However, whether andrographolide has reno-protective roles in DN has not been fully elucidated. Here, we studied the pharmacological effects of andrographolide against the progression of DN and high glucose-induced mesangial dysfunction. Diabetes was induced in C57BL/6 mice by intraperitoneal injection of streptozotocin (STZ). After 1 weeks after STZ injection, normal diet was substituted with a high-fat diet (HFD). Diabetic mice were intraperitoneal injected with andrographolide (2 mg/kg, twice a week). After 8 weeks, functional and histological analyses were carried out. Parallel experiments uncovering the molecular mechanism by which andrographolide prevents from DN was performed in mesangial cells. Andrographolide inhibited the increases in fasting blood glucose, triglyceride, kidney/body weight ratio, blood urea nitrogen, serum creatinine and 24-h albuminuria in diabetic mice. Andrographolide also prevented renal hypertrophy and ECM accumulation. Furthermore, andrographolide markedly attenuated NOX1 expression, ROS production and pro-inflammatory cytokines as well. Additionally, andrographolide inhibited Akt/NF-κB signaling pathway. These results demonstrate that andrographolide is protective against the progression of experimental DN by inhibiting renal oxidative stress, inflammation and fibrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Role of Receptor Tyrosine Kinase Signaling in Renal Fibrosis

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Feng Liu

2016-06-01

Full Text Available Renal fibrosis can be induced in different renal diseases, but ultimately progresses to end stage renal disease. Although the pathophysiologic process of renal fibrosis have not been fully elucidated, it is characterized by glomerulosclerosis and/or tubular interstitial fibrosis, and is believed to be caused by the proliferation of renal inherent cells, including glomerular epithelial cells, mesangial cells, and endothelial cells, along with defective kidney repair, renal interstitial fibroblasts activation, and extracellular matrix deposition. Receptor tyrosine kinases (RTKs regulate a variety of cell physiological processes, including metabolism, growth, differentiation, and survival. Many studies from in vitro and animal models have provided evidence that RTKs play important roles in the pathogenic process of renal fibrosis. It is also showed that tyrosine kinases inhibitors (TKIs have anti-fibrotic effects in basic research and clinical trials. In this review, we summarize the evidence for involvement of specific RTKs in renal fibrosis process and the employment of TKIs as a therapeutic approach for renal fibrosis.

Accumulation of worn-out GBM material substantially contributes to mesangial matrix expansion in diabetic nephropathy

NARCIS (Netherlands)

Kriz, Wilhelm; Loewen, Jana; Federico, Giuseppina; van den Born, Jacob; Groene, Elisabeth; Groene, Hermann Josef

2017-01-01

Thickening of the glomerular basement membrane (GBM) and expansion of the mesangial matrix are hallmarks of diabetic nephropathy (DN), generally considered to emerge from different sites of overproduction: GBM components from podocytes and mesangial matrix from mesangial cells. Reevaluation of 918

The mesangial matrix in the normal and sclerotic glomerulus.

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Rosenblum, N D

1994-02-01

Mesangial sclerosis is a final common pathway to glomerular destruction in a variety of glomerular diseases. The expression of several classes of extracellular matrix (ECM) molecules has been defined in the normal and diseased mesangial matrix (MM). However, the manner in which these ECM components determine the three dimensional structure and function of the MM remains to be defined. Structural studies of the MM suggest that its constituent molecules are regionally organized into subcompartments with different three dimensional structures. The diversity of matrix molecules expressed within the MM as well as the organization of these components in nonrenal ECM's, such as the cornea, provides further support for this organizational model. The study of the cornea has also revealed that novel short chain collagenous proteins partially determine the three dimensional structure of the matrix. Recently, a novel collagen, type VIII collagen, has been described in mesangial cells and in the intact glomerulus. It is hypothesized that type VIII collagen is expressed both as a polymer and as a monomer within the glomerulus, and depending on its conformation, may serve unique functions. In the chronically diseased MM, normal MM components are overexpressed and fibrillar collagens are expressed de novo in a delayed fashion. Enhanced proteoglycan expression, observed early in disease, may determine increased volume of the mesangium. This, in turn, may stimulate the production of fibrillar collagens by mesangial cells resulting in a fibrillar noncompliant mesangial matrix.

Respiratory Syncytial Virus Aggravates Renal Injury through Cytokines and Direct Renal Injury

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Songhui Zhai

2016-09-01

Full Text Available The purpose of this study was to investigate the relationship between renal injury and reinfection that is caused by respiratory syncytial virus (RSV and to analyze the mechanism of renal injury. Rats were repeatedly infected with RSV on days 4, 8, 14, and 28, then sacrificed and examined on day 56 after the primary infection. Renal injury was examined by transmission electron microscopy and histopathology. The F protein of RSV was detected in the renal tissue by indirect immunofluorescence. Proteinuria and urinary glycosaminoglycans (GAGs, serum levels of albumin, urea nitrogen, and creatinine, secretion of cytokines, T lymphocyte population and subsets, and dendritic cell (DC activation state were examined. The results showed that renal injury was more serious in the reinfection group than in the primary infection group. At a higher infection dose, 6×106 PFU, the renal injury was more severe, accompanied by higher levels of proteinuria and urinary GAGs excretion, and lower levels of serum albumin. Podocyte foot effacement was more extensive, and hyperplasia of mesangial cells and proliferation of mesangial matrix were observed. The maturation state of DCs was specific, compared with the primary infection. There was also a decrease in the ratio of CD4+ to CD8+T lymphocytes, due to an increase in the percentage of CD8+T lymphocytes and a decrease in the percentage of CD4+T lymphocytes, and a dramatic increase in the levels of IL-6 and IL-17. In terms of the different reinfection times, the day 14 reinfection group yielded the most serious renal injury and the most significant change in immune function. RSV F protein was still expressed in the glomeruli 56 days after RSV infection. Altogether, these results reveal that RSV infection could aggravate renal injury, which might be due to direct renal injury caused by RSV and the inflammatory lesions caused by the anti-virus response induced by RSV.

Neuraminidase activity mediates IL-6 production by activated lupus-prone mesangial cells.

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Sundararaj, Kamala; Rodgers, Jessalyn I; Marimuthu, Subathra; Siskind, Leah J; Bruner, Evelyn; Nowling, Tamara K

2018-04-01

The development of nephritis is a leading cause of morbidity and mortality in lupus patients. Although the general pathophysiological progression of lupus nephritis is known, the molecular mediators and mechanisms are incompletely understood. Previously, we demonstrated that the glycosphingolipid (GSL) catabolic pathway is elevated in the kidneys of MRL/lpr lupus mice and human lupus patients with nephritis. Specifically, the activity of neuraminidase (NEU) and expression of Neu1, an enzyme in the GSL catabolic pathway is significantly increased. To better understand the role and mechanisms by which this pathway contributes to the progression of LN, we analyzed the expression and effects of NEU activity on the function of MRL/lpr lupus-prone mesangial cells (MCs). We demonstrate that NEU1 and NEU3 promote IL-6 production in MES13 MCs. Neu1 expression, NEU activity, and IL-6 production are significantly increased in stimulated primary MRL/lpr lupus-prone MCs, and blocking NEU activity inhibits IL-6 production. NEU1 and NEU3 expression overlaps IgG deposits in MCs in vitro and in renal sections from nephritic MRL/lpr mice. Together, our results suggest that NEU activity mediates IL-6 production in lupus-prone MCs possibly through an IgG-receptor complex signaling pathway.

Role of TLR4/NADPH oxidase/ROS-activated p38 MAPK in VCAM-1 expression induced by lipopolysaccharide in human renal mesangial cells

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Lee I-Ta

2012-11-01

Full Text Available Abstract Background In bacteria-induced glomerulonephritis, Toll-like receptor 4 (TLR4 activation by lipopolysaccharide (LPS, a key component of the outer membranes of Gram-negative bacteria can increase oxidative stress and the expression of vascular cell adhesion molecule-1 (VCAM-1, which recruits leukocytes to the glomerular mesangium. However, the mechanisms underlying VCAM-1 expression induced by LPS are still unclear in human renal mesangial cells (HRMCs. Results We demonstrated that LPS induced VCAM-1 mRNA and protein levels associated with an increase in the promoter activity of VCAM-1, determined by Western blot, RT-PCR, and promoter assay. LPS-induced responses were inhibited by transfection with siRNAs of TLR4, myeloid differentiation factor 88 (MyD88, Nox2, Nox4, p47phox, c-Src, p38 MAPK, activating transcription factor 2 (ATF2, and p300 or pretreatment with the inhibitors of reactive oxygen species (ROS, edaravone, NADPH oxidase [apocynin (APO or diphenyleneiodonium chloride (DPI], c-Src (PP1, p38 MAPK (SB202190, and p300 (GR343. LPS induced NADPH oxidase activation, ROS production, and p47phox translocation from the cytosol to the membrane, which were reduced by PP1 or c-Src siRNA. We observed that LPS induced TLR4, MyD88, c-Src, and p47phox complex formation determined by co-immunoprecipitation and Western blot. We further demonstrated that LPS stimulated ATF2 and p300 phosphorylation and complex formation via a c-Src/NADPH oxidase/ROS/p38 MAPK pathway. Up-regulation of VCAM-1 led to enhancing monocyte adhesion to HRMCs challenged with LPS, which was inhibited by siRNAs of c-Src, p47phox, p38 MAPK, ATF2, and p300 or pretreatment with an anti-VCAM-1 neutralizing antibody. Conclusions In HRMCs, LPS-induced VCAM-1 expression was, at least in part, mediated through a TLR4/MyD88/ c-Src/NADPH oxidase/ROS/p38 MAPK-dependent p300 and ATF2 pathway associated with recruitment of monocyte adhesion to kidney. Blockade of these pathways may

Can bone marrow differentiate into renal cells?

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Imai, Enyu; Ito, Takahito

2002-10-01

A considerable plasticity of adult stem cells has been confirmed in a wide variety of tissues. In particular, the pluripotency of bone marrow-derived stem cells may influence the regeneration of injured tissues and may provide novel avenues in regenerative medicine. Bone marrow contains at least hematopoietic and mesenchymal stem cells, and both can differentiate into a wide range of differentiated cells. Side population (SP) cells, which are originally defined in bone marrow cells by high efflux of DNA-binding dye, seem to be a new class of multipotent stem cells. Irrespective of the approach used to obtain stem cells, the fates of marrow-derived cells following bone marrow transplantation can be traced by labeling donor cells with green fluorescence protein or by identifying donor Y chromosome in female recipients. So far, bone marrow-derived cells have been reported to differentiate into renal cells, including mesangial cells, endothelial cells, podocytes, and tubular cells in the kidney, although controversy exists. Further studies are required to address this issue. Cell therapy will be promising when we learn to control stem cells such as bone marrow-derived stem cells, embryonic stem cells, and resident stem cells in the kidney. Identification of factors that support stem cells or promote their differentiation should provide a relevant step towards cell therapy.

Vascular smooth muscle cells express the alpha(1A) subunit of a P-/Q-type voltage-dependent Ca(2+)Channel, and It is functionally important in renal afferent arterioles

DEFF Research Database (Denmark)

Hansen, Pernille B. Lærkegaard; Jensen, Boye L.; Andreasen, D

2000-01-01

In the present study, we tested whether the alpha(1A) subunit, which encodes a neuronal isoform of voltage-dependent Ca(2+) channels (VDCCs) (P-/Q-type), was present and functional in vascular smooth muscle and renal resistance vessels. By reverse transcription-polymerase chain reaction...... preglomerular resistance vessels and aorta, as well as mesangial cells, and that P-type VDCCs contribute to Ca(2+) influx in aortic and renal VSMCs and are involved in depolarization-mediated contraction in renal afferent arterioles....

Influence of Acute High Glucose on Protein Abundance Changes in Murine Glomerular Mesangial Cells

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Michelle T. Barati

2016-01-01

Full Text Available The effects of acute exposure to high glucose levels as experienced by glomerular mesangial cells in postprandial conditions and states such as in prediabetes were investigated using proteomic methods. Two-dimensional gel electrophoresis and matrix assisted laser desorption ionization time of flight mass spectrometry methods were used to identify protein expression patterns in immortalized rat mesangial cells altered by 2 h high glucose (HG growth conditions as compared to isoosmotic/normal glucose control (NG⁎ conditions. Unique protein expression changes at 2 h HG treatment were measured for 51 protein spots. These proteins could be broadly grouped into two categories: (1 proteins involved in cell survival/cell signaling and (2 proteins involved in stress response. Immunoblot experiments for a protein belonging to both categories, prohibitin (PHB, supported a trend for increased total expression as well as significant increases in an acidic PHB isoform. Additional studies confirmed the regulation of proteasomal subunit alpha-type 2 and the endoplasmic reticulum chaperone and oxidoreductase PDI (protein disulfide isomerase, suggesting altered ER protein folding capacity and proteasomal function in response to acute HG. We conclude that short term high glucose induces subtle changes in protein abundances suggesting posttranslational modifications and regulation of pathways involved in proteostasis.

Plasma Gelsolin Promotes Proliferation of Mesangial Cell in IgA Nephropathy

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Lei Zhang

2016-12-01

Full Text Available Background/Aims: Plasma gelsolin (pGSN is an actin-binding protein that plays a critical role in the pathogenesis of rheumatoid arthritis. However, whether pGSN is involved in other immunological diseases remains unknown. This study focused on the relationship between pGSN and immunoglobulin A (IgA nephropathy (IgAN. Methods: Two hundred patients with IgAN, 200 patients each with several other types of nephropathy and healthy controls (HCs who underwent kidney biopsies between 2000 and 2014 were enrolled in the study. The Oxford classification system was used to predict the risk of disease progression. Serum and renal tissue were used to detect pGSN, and the correlations between pGSN and IgA, galactose-deficient IgA1 (Gd-IgA1, transforming growth factor beta1 (TGF-β1, fibronectin (FN content, clinical symptoms, and kidney function were analyzed. Results: We found that the pGSN levels were significantly decreased in sera from IgAN patients compared to sera from patients with other forms of glomerular nephritis and HCs. Furthermore, the serum pGSN levels were negatively correlated with the serum IgA1, FN, and TGF-β1 levels, and positively correlated with the estimated glomerular filtration rate. Conversely, the glomerular pGSN content was significantly elevated in the IgAN patients and was positively correlated with TGF-β1 and FN levels. In renal tissue, the pGSN levels were significantly higher in IgAN patients with M1 and S1 compared to patients with M0 and S0 (p in vitro. pGSN also promoted integrin α2β1 expression in HMCs and enhanced the integrin α2β1-pGSN interaction. Conclusion: Our study suggested that pGSN may play an important role in the development of IgAN by promoting the proliferation of mesangial cells and that serum and glomerular pGSN levels may be new markers for predicting IgAN progression and prognosis.

A maladaptive role for EP4 receptors in mouse mesangial cells.

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Guang-xia Yang

Full Text Available Roles of the prostaglandin E2 E-prostanoid 4 receptor (EP4 on extracellular matrix (ECM accumulation induced by TGF-β1 in mouse glomerular mesangial cells (GMCs remain unknown. Previously, we have identified that TGF-β1 stimulates the expression of FN and Col I in mouse GMCs. Here we asked whether stimulation of EP4 receptors would exacerbate renal fibrosis associated with enhanced glomerular ECM accumulation. We generated EP4(Flox/Flox and EP4(+/- mice, cultured primary WT, EP4(Flox/Flox and EP4(+/- GMCs, AD-EP4 transfected WT GMCs (EP4 overexpression and AD-Cre transfected EP4(Flox/Flox GMCs (EP4 deleted. We found that TGF-β1-induced cAMP and PGE2 synthesis decreased in EP4 deleted GMCs and increased in EP4 overexpressed GMCs. Elevated EP4 expression in GMCs augmented the coupling of TGF-β1 to FN, Col I expression and COX2/PGE2 signaling, while TGF-β1 induced FN, Col I expression and COX2/PGE2 signaling were down-regulated in EP4 deficiency GMCs. 8 weeks after 5/6 nephrectomy (Nx, WT and EP4(+/- mice exhibited markedly increased accumulation of ECM compared with sham-operated controls. Albuminuria, blood urea nitrogen and creatinine (BUN and Cr concentrations were significantly increased in WT mice as compared to those of EP4(+/- mice. Urine osmotic pressure was dramatically decreased after 5/6 Nx surgery in WT mice as compared to EP4(+/- mice. The pathological changes in kidney of EP4(+/- mice was markedly alleviated compared with WT mice. Immunohistochemical analysis showed significant reductions of Col I and FN in the kidney of EP4(+/- mice compared with WT mice. Collectively, this investigation established EP4 as a potent mediator of the pro-TGF-β1 activities elicited by COX2/PGE2 in mice GMCs. Our findings suggested that prostaglandin E2, acting via EP4 receptors contributed to accumulation of ECM in GMCs and promoted renal fibrosis.

Hyperglycemia-induced Renal P2X7 Receptor Activation Enhances Diabetes-related Injury

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Robert I. Menzies

2017-05-01

Full Text Available Diabetes is a leading cause of renal disease. Glomerular mesangial expansion and fibrosis are hallmarks of diabetic nephropathy and this is thought to be promoted by infiltration of circulating macrophages. Monocyte chemoattractant protein-1 (MCP-1 has been shown to attract macrophages in kidney diseases. P2X7 receptors (P2X7R are highly expressed on macrophages and are essential components of pro-inflammatory signaling in multiple tissues. Here we show that in diabetic patients, renal P2X7R expression is associated with severe mesangial expansion, impaired glomerular filtration (≤40 ml/min/1.73 sq. m., and increased interstitial fibrosis. P2X7R activation enhanced the release of MCP-1 in human mesangial cells cultured under high glucose conditions. In mice, P2X7R-deficiency prevented glomerular macrophage attraction and collagen IV deposition; however, the more severe interstitial inflammation and fibrosis often seen in human diabetic kidney diseases was not modelled. Finally, we demonstrate that a P2X7R inhibitor (AZ11657312 can reduce renal macrophage accrual following the establishment of hyperglycemia in a model of diabetic nephropathy. Collectively these data suggest that P2X7R activation may contribute to the high prevalence of kidney disease found in diabetics.

Delphinidin prevents high glucose-induced cell proliferation and collagen synthesis by inhibition of NOX-1 and mitochondrial superoxide in mesangial cells

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Seung Eun Song

2016-04-01

Full Text Available This study examined the effect of delphinidin on high glucose-induced cell proliferation and collagen synthesis in mesangial cells. Glucose dose-dependently (5.6–25 mM increased cell proliferation and collagen I and IV mRNA levels, whereas pretreatment with delphinidin (50 μM prevented cell proliferation and the increased collagen mRNA levels induced by high glucose (25 mM. High glucose increased reactive oxygen species (ROS generation, and this was suppressed by pretreating delphinidin or the antioxidant N-acetyl cysteine. NADPH oxidase (NOX 1 was upregulated by high glucose, but pretreatment with delphinidin abrogated this upregulation. Increased mitochondrial superoxide by 25 mM glucose was also suppressed by delphinidin. The NOX inhibitor apocynin and mitochondria-targeted antioxidant Mito TEMPO inhibited ROS generation and cell proliferation induced by high glucose. Phosphorylation of extracellular signal regulated kinase (ERK1/2 was increased by high glucose, which was suppressed by delphinidin, apocynin or Mito TEMPO. Furthermore, PD98059 (an ERK1/2 inhibitor prevented the high glucose-induced cell proliferation and increased collagen mRNA levels. Transforming growth factor (TGF-β protein levels were elevated by high glucose, and pretreatment with delphinidin or PD98059 prevented this augmentation. These results suggest that delphinidin prevents high glucose-induced cell proliferation and collagen synthesis by inhibition of NOX-1 and mitochondrial superoxide in mesangial cells.

Intrinsic renal cells induce lymphocytosis of Th22 cells from IgA nephropathy patients through B7-CTLA-4 and CCL-CCR pathways.

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Gan, Lu; Zhou, Qiaoling; Li, Xiaozhao; Chen, Chen; Meng, Ting; Pu, Jiaxi; Zhu, Mengyuan; Xiao, Chenggen

2018-04-01

IgA nephropathy (IgAN), the most common glomerulonephritis, has an unclear pathogenesis. The role of Th22 cells, which are intimately related to proteinuria and progression in IgAN, in mediating infection-related IgAN is unclear. This study aimed to characterize the association between intrinsic renal cells (tubular epithelial cells and mesangial cells) and Th22 cells in immune regulation of infection-related IgAN and to elucidate the impact of Th22 lymphocytosis; the proinflammatory cytokines IL-1, IL-6, and TNF-α; and CCL chemokines on kidney fibrosis. Hemolytic streptococcus infection induced an increase in IL-1, IL-6, and TNF-α, resulting in Th22 cell differentiation from T lymphocytes obtained from patients with IgAN, and the CCL20-CCR6, CCL22-CCR4, and/or CCL27-CCR10 axes facilitated Th22 cell chemotaxis. The increased amount of Th22 cells caused an increase in TGF-β1 levels, and anti-CD80, anti-CD86, and CTLA-4Ig treatment reduced TGF-β1 levels by inhibiting Th22 lymphocytosis and secretion of cytokines and chemokines, thus potentially relieving kidney fibrosis. Our data suggest that Th22 cells might be recruited into the kidneys via the CCL20-CCR6, CCL22-CCR4, and/or CCL27-CCR10 axes by mesangial cells and tubular epithelial cells in infection-related IgAN. Th22 cell overrepresentation was attributed to stimulation of the B7-CTLA-4Ig antigen-presenting pathway and IL-1, IL-6, and TNF-α.

MiR302 regulates SNAI1 expression to control mesangial cell plasticity

DEFF Research Database (Denmark)

De Chiara, L.; Andrews, D.; Watson, A.

2017-01-01

Cell fate decisions are controlled by the interplay of transcription factors and epigenetic modifiers, which together determine cellular identity. Here we elaborate on the role of miR302 in the regulation of cell plasticity. Overexpression of miR302 effected silencing of the TGFβ type II receptor...... and facilitated plasticity in a manner distinct from pluripotency, characterized by increased expression of Snail. miR302 overexpressing mesangial cells also exhibited enhanced expression of EZH2 coincident with Snail upregulation. esiRNA silencing of each component suggest that Smad3 and EZH2 are part...... of a complex that regulates plasticity and that miR302 regulates EZH2 and Snail independently. Subsequent manipulation of miR302 overexpressing cells demonstrated the potential of using this approach for reprogramming as evidenced by de novo expression of the tight junction components ZO-1 and E...

Resveratrol inhibits PDGF receptor mitogenic signaling in mesangial cells: role of PTP1B

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Venkatesan, Balachandar; Ghosh-Choudhury, Nandini; Das, Falguni; Mahimainathan, Lenin; Kamat, Amrita; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh

2008-01-01

Mesangioproliferative glomerulonephritis is associated with overactive PDGF receptor signal transduction. We show that the phytoalexin resveratrol dose dependently inhibits PDGF-induced DNA synthesis in mesangial cells with an IC50 of 10 μM without inducing apoptosis. Remarkably, the increased SIRT1 deacetylase activity induced by resveratrol was not necessary for this inhibitory effect. Resveratrol significantly blocked PDGF-stimulated c-Src and Akt kinase activation, resulting in reduced cyclin D1 expression and attenuated pRb phosphorylation and cyclin-dependent kinase-2 (CDK2) activity. Furthermore, resveratrol inhibited PDGFR phosphorylation at the PI 3 kinase and Grb-2 binding sites tyrosine-751 and tyrosine-716, respectively. This deficiency in PDGFR phosphorylation resulted in significant inhibition of PI 3 kinase and Erk1/2 MAPK activity. Interestingly, resveratrol increased the activity of protein tyrosine phosphatase PTP1B, which dephosphorylates PDGF-stimulated phosphorylation at tyrosine-751 and tyrosine-716 on PDGFR with concomitant reduction in Akt and Erk1/2 kinase activity. PTP1B significantly inhibited PDGF-induced DNA synthesis without inducing apoptosis. These results for the first time provide evidence that the stilbene resveratrol targets PTP1B to inhibit PDGFR mitogenic signaling.—Venkatesan, B., Ghosh-Choudhury, N., Das, F., Mahimainathan, L., Kamat, A., Kasinath, B. S., Abboud, H. E., Choudhury, G. G. Resveratrol inhibits PDGF receptor mitogenic signaling in mesangial cells: role of PTP1B. PMID:18567737

The in vitro protective effects of curcumin and demethoxycurcumin in Curcuma longa extract on advanced glycation end products-induced mesangial cell apoptosis and oxidative stress.

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Liu, Ji-ping; Feng, Liang; Zhu, Mao-mao; Wang, Ru-Shang; Zhang, Ming-hua; Hu, Shao-ying; Jia, Xiao-bin; Wu, Jin-Jie

2012-11-01

Curcuma longa L. (CLL), a traditional herbal medicine, has been widely used for the prevention of diabetic vascular complications in recent years. However, the protective effects of curcuminoids in CLL on the AGEs-induced damage to mesangial cell are not fully understood. In this present study, dihydroethidium, superoxide dismutase kit, malondialdehyde kit, and acridine orange/ethidium bromide staining methods were used to evaluate the activities of curcumin and demethoxycurcumin (10(-11)-10(-9) M) on AGEs-induced oxidative stress and apoptosis, which were associated with the damage to mesangial cell. The results showed that these two compounds could significantly restore advanced glycation end products (AGEs)-induced apoptosis to normal levels (IC50 = 3.874 × 10(-11) M for curcumin and IC50 = 6.085 × 10(-11) M for demethoxycurcumin) and reduce remarkably reactive oxygen species generation in mesangial cell. Furthermore, curcumin and demethoxycurcumin dramatically elevated AGEs-decreased superoxide dismutase activity while significantly reducing AGEs-increased malondialdehyde content in cell culture supernatant. Our results suggest that both curcumin and demethoxycurcumin have a significant protective potential to the prevention of diabetic nephropathy. Georg Thieme Verlag KG Stuttgart · New York.

Benazepril affects integrin-linked kinase and smooth muscle α-actin expression in diabetic rat glomerulus and cultured mesangial cells.

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Niu, Honglin; Nie, Lei; Liu, Maodong; Chi, Yanqing; Zhang, Tao; Li, Ying

2014-08-20

Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and is associated with excessive cardiovascular morbidity and mortality. The angiotensin converting enzyme inhibitor (ACEI) benazepril has been shown to slow the progression of chronic renal disease and have beneficial effects in patients with a combination of chronic renal disease and cardiovascular disease. Transforming growth factor-β(1) (TGF-β(1)) plays a central role in the pathogenesis and progression of DN. Integrin-linked kinase (ILK) can modulate TGF-β(1)-induced glomerular mesangial cell (GMC) injury, which is a prominent characteristic of renal pathology in kidney diseases. As an integrin cytoplasmic-binding protein, ILK regulates fibronectin (FN) matrix deposition and the actin cytoskeleton. Smooth muscle α-actin (α-SMA) is involved in progressive renal dysfunction in both human and experimental renal disease. To explore the mechanisms of benazepril's reno-protective effects, we examined the expression of TGF-β(1), ILK, and α-SMA in GMC exposed to high glucose (HG) and in the kidneys of streptozotocin (STZ)-induced diabetic rats using real-time quantitative RT-PCR and western blot analysis. To elucidate the mechanism(s) of the effect of benazepril on GMC cellular processes, we assessed the effect of benazepril on Angiotensin II (Ang II) signalling pathways using western blot analysis. The expression of TGF-β(1), ILK, and α-SMA increased significantly in the diabetic group compared with the control group. Benazepril treatment inhibited the expression of these genes in DN but failed to rescue the same levels in the control group. Similar results were found in GMC treated with HG or benazepril. Ang II increased ERK and Akt phosphorylation in the HG group, and benazepril could not completely block these responses, suggesting that other molecules might be involved in the progression of DN. Our findings suggest that benazepril decreases ILK and α-SMA expression, at least in

IGF-1 decreases collagen degradation in diabetic NOD mesangial cells: implications for diabetic nephropathy.

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Lupia, E; Elliot, S J; Lenz, O; Zheng, F; Hattori, M; Striker, G E; Striker, L J

1999-08-01

Nonobese diabetic (NOD) mice develop glomerulosclerosis shortly after the onset of diabetes. We showed that mesangial cells (MCs) from diabetic mice exhibited a stable phenotypic switch, consisting of both increased IGF-1 synthesis and proliferation (Elliot SJ, Striker LJ, Hattori M, Yang CW, He CJ, Peten EP, Striker GE: Mesangial cells from diabetic NOD mice constitutively secrete increased amounts of insulin-like growth factor-I. Endocrinology 133:1783-1788, 1993). Because the extracellular matrix (ECM) accumulation in diabetic glomerulosclerosis may be partly due to decreased degradation, we examined the effect of excess IGF-1 on collagen turnover and the activity of metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) in diabetic and nondiabetic NOD-MC. Total collagen degradation was reduced by 58 +/- 18% in diabetic NOD-MCs, which correlated with a constitutive decrease in MMP-2 activity and mRNA levels, and nearly undetectable MMP-9 activity and mRNA. TIMP levels were slightly decreased in diabetic NOD-MC. The addition of recombinant IGF-1 to nondiabetic NOD-MC resulted in a decrease in MMP-2 and TIMP activity. Furthermore, treatment of diabetic NOD-MC with a neutralizing antibody against IGF-1 increased the latent form, and restored the active form, of MMP-2. In conclusion, the excessive production of IGF-1 contributes to the altered ECM turnover in diabetic NOD-MC, largely through a reduction of MMP-2 activity. These data suggest that IGF-1 could be a major contributor to the development of diabetic glomerulosclerosis.

High Glucose and Lipopolysaccharide Prime NLRP3 Inflammasome via ROS/TXNIP Pathway in Mesangial Cells

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Hong Feng

2016-01-01

Full Text Available While inflammation is considered a central component in the development in diabetic nephropathy, the mechanism remains unclear. The NLRP3 inflammasome acts as both a sensor and a regulator of the inflammatory response. The NLRP3 inflammasome responds to exogenous and endogenous danger signals, resulting in cleavage of procaspase-1 and activation of cytokines IL-1β, IL-18, and IL-33, ultimately triggering an inflammatory cascade reaction. This study observed the expression of NLRP3 inflammasome signaling stimulated by high glucose, lipopolysaccharide, and reactive oxygen species (ROS inhibitor N-acetyl-L-cysteine in glomerular mesangial cells, aiming to elucidate the mechanism by which the NLRP3 inflammasome signaling pathway may contribute to diabetic nephropathy. We found that the expression of thioredoxin-interacting protein (TXNIP, NLRP3, and IL-1β was observed by immunohistochemistry in vivo. Simultaneously, the mRNA and protein levels of TXNIP, NLRP3, procaspase-1, and IL-1β were significantly induced by high glucose concentration and lipopolysaccharide in a dose-dependent and time-dependent manner in vitro. This induction by both high glucose and lipopolysaccharide was significantly inhibited by N-acetyl-L-cysteine. Our results firstly reveal that high glucose and lipopolysaccharide activate ROS/TXNIP/ NLRP3/IL-1β inflammasome signaling in glomerular mesangial cells, suggesting a mechanism by which inflammation may contribute to the development of diabetic nephropathy.

The lymphotoxin β receptor is a potential therapeutic target in renal inflammation.

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Seleznik, Gitta; Seeger, Harald; Bauer, Judith; Fu, Kai; Czerkowicz, Julie; Papandile, Adrian; Poreci, Uriana; Rabah, Dania; Ranger, Ann; Cohen, Clemens D; Lindenmeyer, Maja; Chen, Jin; Edenhofer, Ilka; Anders, Hans J; Lech, Maciej; Wüthrich, Rudolf P; Ruddle, Nancy H; Moeller, Marcus J; Kozakowski, Nicolas; Regele, Heinz; Browning, Jeffrey L; Heikenwalder, Mathias; Segerer, Stephan

2016-01-01

Accumulation of inflammatory cells in different renal compartments is a hallmark of progressive kidney diseases including glomerulonephritis (GN). Lymphotoxin β receptor (LTβR) signaling is crucial for the formation of lymphoid tissue, and inhibition of LTβR signaling has ameliorated several non-renal inflammatory models. Therefore, we tested whether LTβR signaling could also have a role in renal injury. Renal biopsies from patients with GN were found to express both LTα and LTβ ligands, as well as LTβR. The LTβR protein and mRNA were localized to tubular epithelial cells, parietal epithelial cells, crescents, and cells of the glomerular tuft, whereas LTβ was found on lymphocytes and tubular epithelial cells. Human tubular epithelial cells, mesangial cells, and mouse parietal epithelial cells expressed both LTα and LTβ mRNA upon stimulation with TNF in vitro. Several chemokine mRNAs and proteins were expressed in response to LTβR signaling. Importantly, in a murine lupus model, LTβR blockade improved renal function without the reduction of serum autoantibody titers or glomerular immune complex deposition. Thus, a preclinical mouse model and human studies strongly suggest that LTβR signaling is involved in renal injury and may be a suitable therapeutic target in renal diseases. Copyright © 2015 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

[Investigation the Inhibitory Effects of Kaempferol on Rat Renalmesangial Cells Proliferation under High Glucose Condition].

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Chen, Ni; Han, Peng-Ding; Chen, Wen; Deng, Yan

2017-07-01

To investigate the protective effects of kaempferol on rat renal mesangial cells under high glucose condition and explore its mechanism. The HBZY-1 cells were divided into normal glucose group (5.5 mmol/L), high glucose group (25 mmol/L), 10 μmol/L kaempferol+high glucose group, and 30 μmol/L kaempferol+high glucose group. Cell proliferative ability was measured by MTT; cell cycle was analyzed by flow cytometry; mRNA and protein levels were determined by Real-time PCR and Western blot, respectively. Kaempferol had no effect on the proliferative ability of rat renal mesangial cells under normal glucose (5.5 mmol/L) condition. High glucose (25 mmol/L) enhanced the cell proliferative ability, and this effect was antagonized by kaempferol (10-30 μmol/L) treatment. High glucose reduced the cell population at G 0 /G 1 phase with an associated increase in S phase, and had no effect on G₂/M phase; and kaempferol treatment restored high glucose-induced changes in cell cycle. Kaempferol also prevented high glucose-induced increase in fibronectin and connective tissue growth factor mRNA and protein expression levels. Kaempferol also prevented high glucose-induced increase in fibronectin and connective tissue growth factor mRNA and protein expression levels. Further, high glucose caused an increase in protein level of phosphorylated p38 mitogen-activated protein kinases (p38 MAPK), which was antagonized by kaempferol treatment. Our results suggest that kaempferol exerts its protective effect on rat renal mesangial cells under high glucose condition via p38 MAPK signaling pathway.

Qian Yang Yu Yin Granule-containing serum inhibits angiotensin II-induced proliferation, reactive oxygen species production, and inflammation in human mesangial cells via an NADPH oxidase 4-dependent pathway.

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Ding, Kang; Wang, Yan; Jiang, Weimin; Zhang, Yu; Yin, Hongping; Fang, Zhuyuan

2015-03-25

Qian Yang Yu Yin Granule (QYYYG), a traditional Chinese herbal medicine, has been indicated for renal damage in hypertension for decades in China, but little remains known regarding its underlying molecular mechanism. Therefore, we performed the current study in order to investigate the underlying molecular mechanism of QYYYG in the treatment of hypertensive renal damage. We hypothesize that QYYYG relieves hypertensive renal injury through an angiotensin II (Ang II)-nicotinamide adenine dinucleotide phosphate (NAPDH)-oxidase (NOX)-reactive oxygen species (ROS) pathway. In this study, we investigated the effects of QYYYG-containing serum (QYGS) in human mesangial cells (HMCs) against Ang II-induced cell proliferation, ROS production, and inflammation through the seropharmacological method. We found that QYGS could inhibit cell proliferation in Ang II-treated HMCs. In addition, QYGS considerably suppressed production of ROS, decreased mRNA and protein expression of NAPDH-oxidase 4 (NOX4), p22 (phox) , and activated Ras-related C3 botulinum toxin substrate 1 (GTP-Rac1); as well as counteracted the up-regulation of inflammatory markers including tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) p65, and interleukin 6 (IL-6). These effects were further confirmed in HMCs transfected with specific small interfering RNA (siRNA) targeting NOX4. Taken together, these results suggest that a NOX4-dependent pathway plays an important role in regulating the inhibitory effect of QYGS. Our findings provide new insights into the molecular mechanisms of QYYYG and their role in the treatment of hypertensive nephropathy.

Protective Effects of Green Tea Polyphenol Against Renal Injury Through ROS-Mediated JNK-MAPK Pathway in Lead Exposed Rats.

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Wang, Haidong; Li, Deyuan; Hu, Zhongze; Zhao, Siming; Zheng, Zhejun; Li, Wei

2016-06-30

To investigate the potential therapeutic effects of polyphenols in treating Pb induced renal dysfunction and intoxication and to explore the detailed underlying mechanisms. Wistar rats were divided into four groups: control groups (CT), Pb exposure groups (Pb), Pb plus Polyphenols groups (Pb+PP) and Polyphenols groups (PP). Animals were kept for 60 days and sacrificed for tests of urea, serum blood urea nitrogen (BUN) and creatinine. Histological evaluations were then performed. In vitro studies were performed using primary kidney mesangial cells to reveal detailed mechanisms. Cell counting kit-8 (CCK-8) was used to evaluate cell viability. Pb induced cell apoptosis was measured by flow cytometry. Reactive oxygen species (ROS) generation and scavenging were tested by DCFH-DA. Expression level of tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1-β) and IL-6 were assayed by ELISA. Western blot and qPCR were used to measure the expression of ERK1/2, JNK1/2 and p38. Polyphenols have obvious protective effects on Pb induced renal dysfunction and intoxication both in vivo and in vitro. Polyphenols reduced Pb concentration and accumulation in kidney. Polyphenols also protected kidney mesangial cells from Pb induced apoptosis. Polyphenols scavenged Pb induced ROS generation and suppressed ROS-mediated ERK/JNK/p38 pathway. Downstream pro-inflammatory cytokines were inhibited in consistency. Polyphenol is protective in Pb induced renal intoxication and inflammatory responses. The underlying mechanisms lie on the antioxidant activity and ROS scavenging activity of polyphenols.

Resveratrol plays important role in protective mechanisms in renal disease - mini-review

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Guilherme Albertoni

2015-03-01

Full Text Available Resveratrol (RESV is a polyphenolic compound found in various plants, including grapes, berries and peanuts, and its processed foods as red wine. RESV possesses a variety of bioactivities, including antioxidant, anti-inflammatory, cardioprotective, antidiabetic, anticancer, chemopreventive, neuroprotective, renal lipotoxicity preventative, and renal protective effects. Numerous studies have demonstrated that polyphenols promote cardiovascular health. Furthermore, RESV can ameliorate several types of renal injury in animal models, including diabetic nephropathy, hyperuricemic, drug-induced injury, aldosterone-induced injury, ischemia-reperfusion injury, sepsis-related injury, and endothelial dysfunction. In addition, RESV can prevent the increase in vasoconstrictors, such as angiotensin II (AII and endothelin-1 (ET-1, as well as intracellular calcium, in mesangial cells. Together, these findings suggest a potential role for RESV as a supplemental therapy for the prevention of renal injury.

The Renal Allograft Donor with Isolated Microhematuria

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Karkar Ayman

2006-01-01

Full Text Available Recently, there has been extensive debate about extending the criteria for accepting living donors to include the presence of mild renal abnormalities such as isolated microhematuria. Hematuria defined as the detection of greater than five red blood cells per high power field can be associated with abnormalities throughout the urinary tract. Detection of casts or dysmorphic red blood cells in the urine sediment with or without proteinuria could indicate underlying intrinsic renal disease. Anatomic causes, such as stones and tumors, should be excluded; cystoscopy may be indicated to exclude bladder pathology. Obviously, urinary tract infection, uncontrolled hypertension and latent diabetes mellitus must be excluded. Microscopic hematuria could be associated with mesangial IgA deposits; as 10% of first-degree relatives of patients with IgA glomerulonephritis suffer from microhematuria and/or proteinuria that may require consideration of renal biopsy. Microhematuria could also be associated with other known hereditary renal diseases such as C3 deposits disease, IgM nephropathy, autosomal dominant polycystic kidney disease, Alport′s syndrome or thin basement membrane disease. In conclusion, careful assessment of isolated microhematuria, in the context of living kidney donation, is mandatory as results may reveal occult renal disease that may contraindicate kidney donation.

Downregulation of catalase by reactive oxygen species via PI 3 kinase/Akt signaling in mesangial cells.

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Venkatesan, Balachandar; Mahimainathan, Lenin; Das, Falguni; Ghosh-Choudhury, Nandini; Ghosh Choudhury, Goutam

2007-05-01

Reactive oxygen species (ROS) contribute to many glomerular diseases by targeting mesangial cells. ROS have been shown to regulate expression of many antioxidant enzymes including catalase. The mechanism by which the expression of catalase protein is regulated by ROS is not precisely known. Here we report that increased intracellular ROS level by hydrogen peroxide (H(2)O(2)) reduced the expression of catalase. H(2)O(2) increased phosphorylation of Akt kinase in a dose-dependent and sustained manner with a concomitant increase in the phosphorylation of FoxO1 transcription factor. Further analysis revealed that H(2)O(2) promoted rapid activation of phosphatidylinositol (PI) 3 kinase. The PI 3 kinase inhibitor Ly294002 and expression of tumor suppressor protein PTEN inhibited Akt kinase activity, resulting in the attenuation of FoxO1 phosphorylation and preventing the downregulating effect of H(2)O(2) on catalase protein level. Dominant negative Akt attenuated the inhibitory effect of H(2)O(2) on expression of catalase. Constitutively active FoxO1 increased the expression of catalase. However, dominant negative FoxO1 inhibited catalase protein level. Catalase transcription was reduced by H(2)O(2) treatment. Furthermore, expression of dominant negative Akt and constitutively active FoxO1 increased catalase transcription, respectively. These results demonstrate that ROS downregulate the expression of catalase in mesangial cells by PI 3 kinase/Akt signaling via FoxO1 as a target. (c) 2007 Wiley-Liss, Inc.

Cordyceps sinensis protects against renal ischemia/reperfusion injury in rats.

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Wang, Hua-Pin; Liu, Ching-Wen; Chang, Hsueh-Wen; Tsai, Jen-Wei; Sung, Ya-Zhu; Chang, Li-Ching

2013-03-01

Cordyceps sinensis (CS) is an entomogenous fungus used as a tonic food and Chinese medicine to replenish health. This study investigated the protective effects of CS in rats post-renal ischemia-reperfusion (I/R) sequence by analyzing the influence on stromal cell-derived factor-1α (SDF-1α and chemokine (C-X-C motif) receptor 4 (CXCR4) expressions and senescence during recovery. Chemokine SDF-1 [now called chemokine C-X-C motif ligand 12 (CXCL12)] and its receptor CXCR4 are crucial in kidney repair after ischemic acute renal failure. CS treatment significantly alleviated I/R-induced renal damage assessed by creatinine levels (p < 0.05) and abated renal tubular damages assessed by periodic acid-Schiff with diastase (PASD) staining. CS induced early SDF-1α expression and increased CXCR4 expression 1-6 h post-reperfusion. Histology studies have revealed that CS induced SDF-1α in squamous cells of Bowman's capsule, mesangial cells, distal convoluted tubules (DCT), and proximal convoluted tubules (PCT). CS also improved renal repair in I/R-induced injury by increasing Ki-67 staining. I/R induced renal senescence after 3 and 6 h of reperfusion. However, CS alleviated I/R-induced senescence at early stage (1 and 3 h). We conclude that CS protects against I/R injury via the SDF-1/CXCR4-signaling axis and alleviates senescence.

Biphasic effect of oxygen radicals on prostaglandin production by rat mesangial cells

International Nuclear Information System (INIS)

Adler, S.; Stahl, R.A.K.; Baker, P.J.; Chen, Y.P.; Pritzl, P.M.; Couser, W.G.

1987-01-01

Cultured rat mesangial cells were exposed to a reactive oxygen species (ROS) generating system (xanthine plus xanthine oxidase) to explore the effect of ROS on their metabolism of arachidonic acid (AA). Cell viability, as assessed by 51 Cr release, was not affected by the concentrations of xanthine plus xanthine oxidase used. Prostaglandin E 2 (PGE 2 ) production following exposure to increasing quantities of xanthine plus xanthine oxidase was significantly decreased when cells were stimulated with the calcium ionophore A23187 or AA. Maximum suppression of production was seen within 10 min of ROS exposure. Thromboxane B 2 production was similarly decreased. This effect was reversed by addition of catalase to the ROS generating system but not by superoxide dismutase or mannitol, which suggested that H 2 O 2 was the responsible metabolite. High levels of H 2 O 2 suppressed PGE 2 production. Lower levels of H 2 O 2 resulted in significant stimulation of base-line PGE 2 production. Analysis of release of 3 H]AA-labeled metabolites from A23187-stimulated cells showed no effect of H 2 O 2 on phospholipase activity. Thus ROS can stimulate or inhibitor AA metabolism in the glomerular mesangium, which may have important effects on glomerular hemodynamics during glomerular injury

Progressive glomerulosclerosis and renal failure following perinatal gamma radiation in the beagle

International Nuclear Information System (INIS)

Jaenke, R.S.; Phemister, R.D.; Norrdin, R.W.

1980-01-01

The renal effects of whole body irradiation in the perinatal period were studied in the dog. Ninety-three dogs received a single sublethal exposure in the range of 270 to 435 R in either late gestation (55 days postcoitus) or early postnatal life (2 days postpartum) and were sacrificed at 70 days, 2, or 4 years of age. Early renal lesions in 70-day-old irradiated dogs were characterized by arrested glomerular maturation and degeneration resulting in reduced functional renal mass. Mature glomeruli exhibited mesangial proliferation. At 2 and 4 years of age, surviving irradiated dogs exhibited sever renal disease associated with progressive glomerular damage which was characterized by mesangial proliferation and compression of capillary lumina, epithelial degeneration and focal capsular adhesions, and ultimately obliterative glomerulosclerosis. Twenty-one of the 93 irradiated dogs died in renal failure before 4 years of age with advanced glomerulosclerosis. The phatogenesis of this progressive renal lesion may be related to the interaction of three specific factors. These include (1) the effect of direct radiation damage to mature kidney components; (2) the loss of outer cortical nephrons resulting in increased work load of the surviving nephrons; and (3) the effect of compensatory hypertrophy related to the loss of renal parenchyma as the rapid growth rates associated with kidney maturation

AOPPs Induce MCP-1 Expression by Increasing ROS-Mediated Activation of the NF-κB Pathway in Rat Mesangial Cells: Inhibition by Sesquiterpene Lactones

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Jian-Cheng Wang

2013-12-01

Full Text Available Background: Monocyte chemoattractant protein-1 (MCP-1 plays an important role in extracellular matrix accumulation through macrophage recruitment and activation in the development and progression of diabetic nephropathy. Therefore, this study examined whether advanced oxidation protein products (AOPPs are involved in nuclear factor-κB (NF-κB activation and MCP-1 mRNA and protein expression in mesangial cells (MCs and evaluated the effects of derivatives of sesquiterpene lactones (SLs on AOPP-induced renal damage. Methods: MCP-1 mRNA and protein expression in MCs were determined by quantitative real-time PCR and ELISA, respectively. The level of intracellular reactive oxygen species (ROS was determined by flow cytometry. The protein expression of tubulin, P47, NF-κB p65, phospho-NF-κB p65, IκB, phospho-IκB, IKKß and phospho-IKKß was evaluated by Western blot. Results: AOPPs caused oxidative stress in MCs and activated the NF-κB pathway by inducing IκBa phosphorylation and degradation. Inhibition of ROS by SOD (ROS inhibitor blocked the AOPP-mediated NF-κB pathway. Moreover, the inhibition of AOPP-induced overproduction of MCP-1 mRNA and protein was associated with inhibition of IκBa degradation by SLs. Conclusion: AOPPs induce MCP-1 expression by activating the ROS/NF-κB pathway and can be inhibited by SLs. These findings may provide a novel approach to treat inflammatory and immune renal diseases, including diabetic nephropathy.

Upregulated expression of integrin α1 in mesangial cells and integrin α3 and vimentin in podocytes of Col4a3-null (Alport mice.

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Brooke M Steenhard

Full Text Available Alport disease in humans, which usually results in proteinuria and kidney failure, is caused by mutations to the COL4A3, COL4A4, or COL4A5 genes, and absence of collagen α3α4α5(IV networks found in mature kidney glomerular basement membrane (GBM. The Alport mouse harbors a deletion of the Col4a3 gene, which also results in the lack of GBM collagen α3α4α5(IV. This animal model shares many features with human Alport patients, including the retention of collagen α1α2α1(IV in GBMs, effacement of podocyte foot processes, gradual loss of glomerular barrier properties, and progression to renal failure. To learn more about the pathogenesis of Alport disease, we undertook a discovery proteomics approach to identify proteins that were differentially expressed in glomeruli purified from Alport and wild-type mouse kidneys. Pairs of cy3- and cy5-labeled extracts from 5-week old Alport and wild-type glomeruli, respectively, underwent 2-dimensional difference gel electrophoresis. Differentially expressed proteins were digested with trypsin and prepared for mass spectrometry, peptide ion mapping/fingerprinting, and protein identification through database searching. The intermediate filament protein, vimentin, was upregulated ∼2.5 fold in Alport glomeruli compared to wild-type. Upregulation was confirmed by quantitative real time RT-PCR of isolated Alport glomeruli (5.4 fold over wild-type, and quantitative confocal immunofluorescence microscopy localized over-expressed vimentin specifically to Alport podocytes. We next hypothesized that increases in vimentin abundance might affect the basement membrane protein receptors, integrins, and screened Alport and wild-type glomeruli for expression of integrins likely to be the main receptors for GBM type IV collagen and laminin. Quantitative immunofluorescence showed an increase in integrin α1 expression in Alport mesangial cells and an increase in integrin α3 in Alport podocytes. We conclude that

Presence of. gamma. G and. beta. 1C globulins in renal glomeruli of aging and neonatally x-irradiated mice

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Guttman, P H; Wuepper, K D; Fudenberg, H H

1967-01-01

A renal lesion in rodents, termed progressive intercapillary glomerulosclerosis (IGS), is characterized by gradual increase in the thickness of the mesangium due to cell proliferation, clustering, and pleomorphism of the mesangial cells, accumulation of PAS-positive mesangial matrix and progressive increase in the thickness of capillary basement membranes. Electron microscopy reveals deposits of electron-dense material in kidneys with IGS suggestive of plasma proteins in the mesangial matrix and in the basement membranes. IGS appears early in life and progresses with age. Whole body irradiation or direct irradiation of the kidneys causes acceleration of the glomerular lesion. A latent period precedes the onset of demonstrable histologic changes following x-ray; this latent period is of shorter duration in animals irradiated late in life. In previous studies, the possible role of an immune mechanism in the pathogenesis of IGS was suggested by the following observations: (1) the progressive course of the disease after a latent period following a single exposure to x-ray; (2) the similarity of the lesions to those seen in experimental immune disease of the kidney in rodents; (3) the presence of electron-dense material suggesting plasma protein deposits in the basement membranes and matrix; and (4) the potentiating effect of neonatal thymectomy on the course of radiation-induced IGS.

Renal cell carcinoma in patient with crossed fused renal ectopia

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Ozgur Cakmak

2016-01-01

Full Text Available Primary renal cell carcinomas have rarely been reported in patients with crossed fused renal ectopia. We presented a patient with right to left crossed fused kidney harbouring renal tumor. The most frequent tumor encountered in crossed fused renal ectopia is renal cell carcinoma. In this case, partial nephrectomy was performed which pave way to preservation of the uninvolved both renal units. Due to unpredictable anatomy, careful preoperative planning and meticulous delineation of renal vasculature is essential for preservation of the uninvolved renal units.

Follistatin, an Activin Antagonist, Ameliorates Renal Interstitial Fibrosis in a Rat Model of Unilateral Ureteral Obstruction

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Akito Maeshima

2014-01-01

Full Text Available Activin, a member of the TGF-β superfamily, regulates cell growth and differentiation in various cell types. Activin A acts as a negative regulator of renal development as well as tubular regeneration after renal injury. However, it remains unknown whether activin A is involved in renal fibrosis. To clarify this issue, we utilized a rat model of unilateral ureteral obstruction (UUO. The expression of activin A was significantly increased in the UUO kidneys compared to that in contralateral kidneys. Activin A was detected in glomerular mesangial cells and interstitial fibroblasts in normal kidneys. In UUO kidneys, activin A was abundantly expressed by interstitial α-SMA-positive myofibroblasts. Administration of recombinant follistatin, an activin antagonist, reduced the fibrotic area in the UUO kidneys. The number of proliferating cells in the interstitium, but not in the tubules, was significantly lower in the follistatin-treated kidneys. Expression of α-SMA, deposition of type I collagen and fibronectin, and CD68-positive macrophage infiltration were significantly suppressed in the follistatin-treated kidneys. These data suggest that activin A produced by interstitial fibroblasts acts as a potent profibrotic factor during renal fibrosis. Blockade of activin A action may be a novel approach for the prevention of renal fibrosis progression.

Stages of Renal Cell Cancer

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... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

Hyperglycemia induces elevated expression of thyroid hormone binding protein in vivo in kidney and heart and in vitro in mesangial cells

International Nuclear Information System (INIS)

Al-Kafaji, Ghada; Malik, Afshan N.

2010-01-01

During a search for glucose-regulated abundant mRNAs in the diabetic rat kidney, we cloned thyroid hormone binding protein (THBP), also known as μ-crystallin or CRYM. The aim of this study was to investigate the effect of hyperglycemia/high glucose on the expression of THBP. THBP mRNA copy numbers were determined in kidneys and hearts of diabetic GK rats vs normoglycemic Wistar rats, and in human mesangial cells (HMCs) exposed to high glucose using real-time qPCR, and THBP protein levels were measured by Western blotting and immunofluorescence. Intracellular ROS was measured in THBP transfected cells using DCF fluorescence. Hyperglycemia significantly increased THBP mRNA in GK rat kidneys (326 ± 50 vs 147 ± 54, p < 0.05), and hearts (1583 ± 277 vs 191 ± 63, p < 0.05). Moreover, the levels of THBP mRNA increased with age and hyperglycemia in GK rat kidneys, whereas in normoglycemic Wistar rat kidneys there was a decline with age. High glucose significantly increased THBP mRNA (92 ± 37 vs 18 ± 4, p < 0.005), and protein in HMCs. The expression of THBP as a fusion protein in transfected HMCs resulted in reduction of glucose-induced intracellular ROS. We have shown that THBP mRNA is increased in diabetic kidney and heart, is regulated by high glucose in renal cells, and appears to attenuate glucose-induced intracellular ROS. These data suggest that THBP may be involved in the cellular pathways activated in response to glucose. This is the first report linking hyperglycemia with THBP and suggests that the role of THBP in diabetic complications should be further investigated.

Hyperglycemia induces elevated expression of thyroid hormone binding protein in vivo in kidney and heart and in vitro in mesangial cells

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Al-Kafaji, Ghada [Diabetes Research Group, Division of Reproduction and Endocrinology, King' s College London (United Kingdom); Malik, Afshan N., E-mail: afshan.malik@kcl.ac.uk [Diabetes Research Group, Division of Reproduction and Endocrinology, King' s College London (United Kingdom)

2010-01-22

During a search for glucose-regulated abundant mRNAs in the diabetic rat kidney, we cloned thyroid hormone binding protein (THBP), also known as {mu}-crystallin or CRYM. The aim of this study was to investigate the effect of hyperglycemia/high glucose on the expression of THBP. THBP mRNA copy numbers were determined in kidneys and hearts of diabetic GK rats vs normoglycemic Wistar rats, and in human mesangial cells (HMCs) exposed to high glucose using real-time qPCR, and THBP protein levels were measured by Western blotting and immunofluorescence. Intracellular ROS was measured in THBP transfected cells using DCF fluorescence. Hyperglycemia significantly increased THBP mRNA in GK rat kidneys (326 {+-} 50 vs 147 {+-} 54, p < 0.05), and hearts (1583 {+-} 277 vs 191 {+-} 63, p < 0.05). Moreover, the levels of THBP mRNA increased with age and hyperglycemia in GK rat kidneys, whereas in normoglycemic Wistar rat kidneys there was a decline with age. High glucose significantly increased THBP mRNA (92 {+-} 37 vs 18 {+-} 4, p < 0.005), and protein in HMCs. The expression of THBP as a fusion protein in transfected HMCs resulted in reduction of glucose-induced intracellular ROS. We have shown that THBP mRNA is increased in diabetic kidney and heart, is regulated by high glucose in renal cells, and appears to attenuate glucose-induced intracellular ROS. These data suggest that THBP may be involved in the cellular pathways activated in response to glucose. This is the first report linking hyperglycemia with THBP and suggests that the role of THBP in diabetic complications should be further investigated.

Bilateral papillary renal cell carcinoma

International Nuclear Information System (INIS)

Gossios, K.; Vazakas, P.; Argyropoulou, M.; Stefanaki, S.; Stavropoulos, N.E.

2001-01-01

Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. We report the clinical and imaging findings of a case with multifocal and bilateral renal cell carcinoma which are nonspecific. (orig.)

CT differentiation of infiltrating renal cell carcinoma and renal urothelial tumor

International Nuclear Information System (INIS)

Choi, Hyo Kyeong; Goo, Dong Erk; Bang, Sun Woo; Lee, Moon Gyu; Cho, Kyoung Sik; Auh, Yong Ho

1994-01-01

It may be difficult to differentiate renal cell carcinoma involving collecting system from renal urothelial tumor invading into renal parenchyma. The purpose of this study was to assess the differences of CT findings between two conditions. CT findings of 5 cases of renal cell carcinoma involving the renal collecting systems and 10 cases of renal urothelial tumors invading the renal parenchyma were compared, and analyzed about the presence or absence of hydronephrosis, normal or abnormal CT nephrogram, renal contour changes due to mass and tentative diagnosis. The diagnoses were confirmed at surgery. Renal cell carcinoma showed hydronephrosis in only 20% and normal CT nephrogram and outward contour bulging in all cases. In contrast, renal urothelial tumor showed hydronephrosis(70%), abnormal CT nephrogram(60%), and preservation of reinform shape(100%). Renal contour changes and CT nephrogram may be useful in distinguishing both disease entities

Astragaloside IV prevents damage to human mesangial cells through the inhibition of the NADPH oxidase/ROS/Akt/NF‑κB pathway under high glucose conditions.

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Sun, Li; Li, Weiping; Li, Weizu; Xiong, Li; Li, Guiping; Ma, Rong

2014-07-01

Glomerular hypertrophy and hyperfiltration are the two major pathological characteristics of the early stages of diabetic nephropathy (DN), which are respectively related to mesangial cell (MC) proliferation and a decrease in calcium influx conducted by canonical transient receptor potential cation channel 6 (TRPC6). The marked increase in the production of reactive oxygen species (ROS) induced by hyperglycemia is the main sponsor of multiple pathological pathways in DN. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of ROS production in MCs. Astragaloside IV (AS‑IV) is an active ingredient of Radix Astragali which has a potent antioxidative effect. In this study, we aimed to investigate whether high glucose (HG)‑induced NADPH oxidase activation and ROS production contribute to MC proliferation and the downregulation of TRPC6 expression; we also wished to determine the effects of AS‑IV on MCs under HG conditions. Using a human glomerular mesangial cell line, we found that treatment with AS‑IV for 48 h markedly attenuated HG‑induced proliferation and the hypertrophy of MCs in a dose‑dependent manner. The intracellular ROS level was also markedly reduced following treatment with AS‑IV. In addition, the enhanced activity of NADPH oxidase and the expression level of NADPH oxidase 4 (Nox4) protein were decreased. Treatment with AS‑IV also inhibited the phosphorylation level of Akt and IκBα in the MCs. In addition, TRPC6 protein expression and the intracellular free calcium concentration were also markedly reduced following treatment with AS‑IV under HG conditions. These results suggest that AS‑IV inhibits HG‑induced mesangial cell proliferation and glomerular contractile dysfunction through the NADPH oxidase/ROS/Akt/nuclear factor‑κB (NF‑κB) pathway, providing a new perspective for the clinical treatment of DN.

Increased response to oxidative stress challenge of nano-copper-induced apoptosis in mesangial cells

International Nuclear Information System (INIS)

Xu, Pengjuan; Li, Zhigui; Zhang, Xiaochen; Yang, Zhuo

2014-01-01

Recently, many studies reported that nanosized copper particles (nano-Cu, the particle size was around 15–30 nm), one of the nanometer materials, could induce nephrotoxicity. To detect the effect of nano-Cu on mesangial cells (MCs), and investigate the underlying mechanism, MCs were treated with different concentrations of nano-Cu (1, 10, and 30 μg/mL) to determine the oxidative stress and apoptotic changes. It was revealed that nano-Cu could induce a decreased viability in MCs together with a significant increase in the number of apoptotic cells by using cell counting kit-8 assay and flow cytometry. The apoptotic morphological changes induced by nano-Cu in MCs were demonstrated by Hochest33342 staining. Results showed that nano-Cu induced the nuclear fragmentation in MCs. Meanwhile, nano-Cu significantly increased the levels of reactive oxygen species, especially increased the levels of H 2 O 2 . It also decreased the activity of total SOD enzyme. In addition, when pre-treated with N-(2-mercaptopropionyl)-glycine, the cell apoptosis induced by nano-Cu was significantly decreased. These results suggest that oxidative stress plays an important role in the nano-Cu toxicity in MCs, which may be the main mechanism of nano-Cu-induced nephrotoxicity

Opposite regulation of type II and III receptors for immunoglobulin G in mouse glomerular mesangial cells and in the induction of anti-glomerular basement membrane (GBM) nephritis

NARCIS (Netherlands)

Radeke, HH; Janssen-Graalfs, [No Value; Sowa, EN; Chouchakova, N; Skokowa, J; Loscher, F; Schmidt, RE; Heeringa, P; Gessner, JE

2002-01-01

We examined the capacity of mouse glomerular mesangial cells (MC) to express and function through two different low affinity FcgammaRs, the activating FcgammaRIII and the inhibitory FcgammaRII. Immunohistochemistry identified FcgammaRII as the prominent FcgammaR in the kidney, and low levels of

CT differentiation of renal tumor invading parenchyma and pelvis: renal cell carcinoma vs transitional cell carcinoma

International Nuclear Information System (INIS)

Lee, Chang Hee; Cho, Seong Beum; Park, Cheol Min; Cha, In Ho; Chung, Kyoo Byung

1994-01-01

The differentiation between renal cell carcinoma(RCC) and transitional cell carcinoma(TCC) is important due to the different methods of treatment and prognosis. But occasionally it is difficult to draw a distinction between the two diseases when renal parenchyma and renal collecting systems are invaded simultaneously. We reviewed CT scans of 37 cases of renal cell carcinoma and 12 cases of transitional cell carcinoma which showed involvement of renal parenchyma and renal sinus fat on CT. Retrospective analysis was performed by 3 abdominal radiologists. Check points were renal contour bulging or reinform shape, location of mass center, intact parenchyma overlying the tumor, cystic change, calcification, LN metastasis, vessel invasion, and perirenal extention. There were renal contour bulging due to the tumor mass in 33 out of 37 cases of renal cell carcinoma, where a and nine of 12 cases of transitional cell carcinoma maintained the reinform appearance. This is significant statiscal difference between the two(P<0.005). Center of all TCCs were located in the renal sinus, and 24 out of 35 cases of RCC were located in the cortex(P<0.005). Thirty-six out of 37 cases of RCC lost the overlying parenchyma, where as 4 out of 9 cases of well enhanced TCC had intact overlying parenchyma(P<0.005) RCC showed uptic change within the tumor mags in 31 cases which was significanity higher than the 4 cases in TCC(P<0.05). CT findings of renal cell carcinoma are contour bulging, peripheral location, obliteration of parenchyma, and cystic change. Findings of transitional cell carcinoma are reinform appearance, central location within the kidney, intact overlying parenchyma, and rare cystic change

Renal alterations in feline immunodeficiency virus (FIV)-infected cats: a natural model of lentivirus-induced renal disease changes.

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Poli, Alessandro; Tozon, Natasa; Guidi, Grazia; Pistello, Mauro

2012-09-01

Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.

General Information about Renal Cell Cancer

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... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

Treatment Option Overview (Renal Cell Cancer)

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... Tumors Treatment Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional Version Key Points Renal ...

Involvement of F-Actin in Chaperonin-Containing t-Complex 1 Beta Regulating Mouse Mesangial Cell Functions in a Glucose-Induction Cell Model

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Jin-Shuen Chen

2011-01-01

Full Text Available The aim of this study is to investigate the role of chaperonin-containing t-complex polypeptide 1 beta (CCT2 in the regulation of mouse mesangial cell (mMC contraction, proliferation, and migration with filamentous/globular-(F/G- actin ratio under high glucose induction. A low CCT2 mMC model induced by treatment of small interference RNA was established. Groups with and without low CCT2 induction examined in normal and high (H glucose conditions revealed the following major results: (1 low CCT2 or H glucose showed the ability to attenuate F/G-actin ratio; (2 groups with low F/G-actin ratio all showed less cell contraction; (3 suppression of CCT2 may reduce the proliferation and migration which were originally induced by H glucose. In conclusion, CCT2 can be used as a specific regulator for mMC contraction, proliferation, and migration affected by glucose, which mechanism may involve the alteration of F-actin, particularly for cell contraction.

Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal

DEFF Research Database (Denmark)

Mitchell, Thomas J.; Turajlic, Samra; Rowan, Andrew

2018-01-01

Clear cell renal cell carcinoma (ccRCC) is characterized by near-universal loss of the short arm of chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cell carcinoma. We find hotspots of point mutations in the...

ERK Regulates Renal Cell Proliferation and Renal Cyst Expansion in inv Mutant Mice

International Nuclear Information System (INIS)

Okumura, Yasuko; Sugiyama, Noriyuki; Tanimura, Susumu; Nishida, Masashi; Hamaoka, Kenji; Kohno, Michiaki; Yokoyama, Takahiko

2009-01-01

Nephronophthisis (NPHP) is the most frequent genetic cause of end-stage kidney disease in children and young adults. Inv mice are a model for human nephronophthisis type 2 (NPHP2) and characterized by multiple renal cysts and situs inversus. Renal epithelial cells in inv cystic kidneys show increased cell proliferation. We studied the ERK pathway to understand the mechanisms that induce cell proliferation and renal cyst progression in inv kidneys. We studied the effects of ERK suppression by administering PD184352, an oral mitogen-activated protein kinase kinase (MEK) inhibitor on renal cyst expansion, extracellular signal-regulated protein kinase (ERK) activity, bromo-deoxyuridine (BrdU) incorporation and expression of cell-cycle regulators in invΔC kidneys. Phosphorylated ERK (p-ERK) level increased along with renal cyst enlargement. Cell-cycle regulators showed a high level of expression in invΔC kidneys. PD184352 successfully decreased p-ERK level and inhibited renal cyst enlargement. The inhibitor also decreased expression of cell-cycle regulators and BrdU incorporation in renal epithelial cells. The present results showed that ERK regulated renal cell proliferation and cyst expansion in inv mutants

Renal Alterations in Feline Immunodeficiency Virus (FIV-Infected Cats: A Natural Model of Lentivirus-Induced Renal Disease Changes

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Mauro Pistello

2012-08-01

Full Text Available Human immunodeficiency virus (HIV is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.

Computed tomography of renal cell carcinoma in patients with terminal renal impairment

International Nuclear Information System (INIS)

Ferda, Jiri; Hora, Milan; Hes, Ondrej; Reischig, Tomas; Kreuzberg, Boris; Mirka, Hynek; Ferdova, Eva; Ohlidalova, Kristyna; Baxa, Jan; Urge, Tomas

2007-01-01

Purpose: An increased incidence of renal tumors has been observed in patients with end-stage-renal-disease (ESRD). The very strong association with acquired renal cystic disease (ACRD) and increased incidence of the renal tumors (conventional renal cell carcinoma (CRCC), papillary renal cell carcinoma (PRCC) or papillary renal cell adenoma (PRCA)) was reported. This study discusses the role of computed tomography (CT) in detecting renal tumors in patients with renal impairment: pre-dialysis, those receiving dialysis or with renal allograft transplants. Materials and methods: Ten patients (nine male, one female) with renal cell tumors were enrolled into a retrospective study; two were new dialysis patients, three on long-term dialysis, and five were renal transplant recipients with history of dialysis. All patients underwent helical CT, a total of 11 procedures were performed. Sixteen-row detector system was used five times, and a 64-row detector system for the six examinations. All patients underwent nephrectomy of kidney with suspected tumor, 15 nephrectomies were performed, and 1 kidney was assessed during autopsy. CT findings were compared with macroscopic and microscopic assessments of the kidney specimen in 16 cases. Results: Very advanced renal parenchyma atrophy with small cysts corresponding to ESRD was found in nine patients, chronic pyelonephritis in remained one. A spontaneously ruptured tumor was detected incidentally in one case, patient died 2 years later. In the present study, 6.25% (1/16) were multiple PRCA, 12.5% (2/16) were solitary PRCC, 12.5% tumors (2/16) were solitary conventional renal cell carcinomas (CRCC's), 12.5% tumors (2/16) were multiple conventional renal cell carcinomas (CRCC's), 25% (4/16) were CRCC's combined with multiple papillary renal cell carcinomas with adenomas (PRCC's and PRCA's), and 25% (4/16) of the tumors were multiple PRCC's combined with PRCA's without coexisting CRCC's. Bilateral renal tumors were found in our study

Renal protection in diabetes--an emerging role for calcium antagonists

DEFF Research Database (Denmark)

Parving, H H; Tarnow, L; Rossing, P

1997-01-01

The combination of diabetes and hypertension increases the changes of progressive renal disorder and ultimately renal failure. Roughly 40% of all diabetics, whether insulin dependent or not, develop diabetic nephropathy. Diabetic nephropathy is the single most important cause of end-stage renal...... disease in the western world and accounts for more than a quarter of all end-stage renal diseases. It is also a major cause of increased morbidity and mortality in diabetic patients. Increased arterial blood pressure is an early and common phenomenon in incipient and overt diabetic nephropathy...... the ability to retard renal growth and possibly to attenuate mesangial entrapment of macromolecules and to attenuate the mitogenic effects of diverse growth factors. Calcium antagonists (except the old short-acting dihydropyridine drugs) reduce microalbuminuria and preserve kidney function in diabetic...

Chromophobe Renal Cell Carcinoma is the Most Common Nonclear Renal Cell Carcinoma in Young Women: Results from the SEER Database.

Science.gov (United States)

Daugherty, Michael; Blakely, Stephen; Shapiro, Oleg; Vourganti, Srinivas; Mollapour, Mehdi; Bratslavsky, Gennady

2016-04-01

The renal cell cancer incidence is relatively low in younger patients, encompassing 3% to 7% of all renal cell cancers. While young patients may have renal tumors due to hereditary syndromes, in some of them sporadic renal cancers develop without any family history or known genetic mutations. Our recent observations from clinical practice have led us to hypothesize that there is a difference in histological distribution in younger patients compared to the older cohort. We queried the SEER (Surveillance, Epidemiology and End Results) 18-registry database for all patients 20 years old or older who were surgically treated for renal cell carcinoma between 2001 and 2008. Patients with unknown race, grade, stage or histology and those with multiple tumors were excluded from study. Four cohorts were created by dividing patients by gender, including 1,202 females and 1,715 males younger than 40 years old, and 18,353 females and 30,891 males 40 years old or older. Chi-square analysis was used to compare histological distributions between the cohorts. While clear cell carcinoma was still the most common renal cell cancer subtype across all genders and ages, chromophobe renal cell cancer was the most predominant type of nonclear renal cell cancer histology in young females, representing 62.3% of all nonclear cell renal cell cancers (p renal cell cancer remained the most common type of nonclear renal cell cancer. It is possible that hormonal factors or specific pathway dysregulations predispose chromophobe renal cell cancer to develop in younger women. We hope that this work provides some new observations that could lead to further studies of gender and histology specific renal tumorigenesis. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Renal diseases related to MYH9 disorders].

Science.gov (United States)

Galeano, Dario; Zanoli, Luca; L'Imperio, Vincenzo; Fatuzzo, Pasquale; Granata, Antonio

2017-04-01

Mutations in MYH9 gene encoding the nonmuscle myosin heavy chain IIA (NMMHC-IIA) are related to a number of rare autosomal-dominant disorders which has been known as May-Hegglin disease, Sebastian syndrome, Fechtner syndrome and Epstein syndrome. Their common clinical features are congenital macrothrombocytopaenia and polymorphonuclear inclusion bodies, in addition to a variable risk of developing proteinuria, chronic kidney disease progressing toward end stage, sensorineural deafness and presenile cataracts. The term MYH9 related disease (MYH9-RD) describes the variable expression of a single illness encompassing all previously mentioned hereditary disorders. Renal involvement in MYH9- RD has been observed in 30% of patients. Mutant MYH9 protein, expressed in podocytes, mesangial and tubular cells, plays a main role in foot process effacement and in development of nephropathy. Interestingly, the MYH9 gene is currently under investigation also for his possible contribution to many other non-hereditary glomerulopathies such as focal global glomerulosclerosis (hypertensive nephrosclerosis), idiopathic focal segmental glomerulosclerosis, C1q nephropathy and HIV-associated nephropathy. In this review we are aimed to describe renal diseases related to MYH9 disorders, from the hereditary disease to the acquired disorders, in which MYH9-gene acts as a "renal failure susceptibility gene". Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Andrographolide suppresses high glucose-induced fibronectin expression in mesangial cells via inhibiting the AP-1 pathway.

Science.gov (United States)

Lan, Tian; Wu, Teng; Gou, Hongju; Zhang, Qianqian; Li, Jiangchao; Qi, Cuiling; He, Xiaodong; Wu, Pingxiang; Wang, Lijing

2013-11-01

Mesangial cells (MCs) proliferation and accumulation of glomerular matrix proteins such as fibronectin (FN) are the early features of diabetic nephropathy, with MCs known to upregulate matrix protein synthesis in response to high glucose. Recently, it has been found that andrographolide has renoprotective effects on diabetic nephropathy. However, the molecular mechanism underlying these effects remains unclear. Cell viability and proliferation was evaluated by MTT. FN expression was examined by immunofluorescence and immunoblotting. Activator protein-1 (AP-1) activation was assessed by immunoblotting, luciferase reporter and electrophoretic mobility shift assays. Andrographolide significantly decreased high glucose-induced cell proliferation and FN expression in MCs. Exposure of MCs to high glucose markedly stimulated the expression of phosphorylated c-jun, whereas the stimulation was inhibited by andrographolide. Plasmid pAP-1-Luc luciferase reporter assay showed that andrographolide blocked high glucose-induced AP-1 transcriptional activity. EMSA assay demonstrated that increased AP-1 binding to an AP-1 binding site at -1,029 in the FN gene promoter upon high glucose stimulation, and the binding were disrupted by andrographolide treatment. These data indicate that andrographolide suppresses high glucose-induced FN expression by inhibiting AP-1-mediated pathway. © 2013 Wiley Periodicals, Inc.

Clinical meanings of changes of blood expression of CD95 antigen (Fas), Bcl-2 and transforming growth factor-α (TGF-α) in patients with chronic renal failure on hemodialysis

International Nuclear Information System (INIS)

Yang Daoli; Luo Nanping; Sun Xiaoming

2005-01-01

Objective: To study the changes of expression of blood CD95 antigen (Fas), and anti-apoptosis factor (Bcl-2) and TGF-α after hemodialysis in patients with chronic renal failure. Methods: The percentage of CD95 and Bcl-2 positive cells in peripheral blood monocytes were examined with flow cytometry and serum TGF-α contents were measured with RIA in 40 patients with chronic renal failure both before and after hemodialysis as well as in 25 other patients with chronic renal failure but not on dialysis and 30 controls. Results: Expressions of CD95 were significantly higher and expressions of Bcl-2, TGF-α were significantly lower in all the patients with chronic renal failure than those in the controls (P 0.05). Conclusion: The up-regulation of CD95 expression and increase of serum TGF-α contents after hemodialysis might contribute to induction of apoptosis of mesangial cells, which would be beneficial to the patient. (authors)

Abatacept Treatment Does Not Preserve Renal Function in the Streptozocin-Induced Model of Diabetic Nephropathy.

Directory of Open Access Journals (Sweden)

Jenny Norlin

Full Text Available Diabetic nephropathy (DN is one of the most severe complications of diabetes and remains the largest cause of end-stage renal disease in the Western world. Treatment options are limited and novel therapies that effectively slow disease progression are warranted. Previous work suggested that treatment with CTLA4-Ig (abatacept, a molecule that binds and blocks B7-1 and is licensed for the treatment of rheumatoid arthritis, could ameliorate DN. This study was designed to assess whether B7-1 signalling constitutes a promising therapeutic pathway for DN. Mice injected with streptozotocin (STZ were treated with abatacept and glycemia and renal function were assessed. No differences were found in diabetes progression, albumin excretion rates or albumin/creatine ratios, while mesangial expansion was unaltered at endpoint. Except for increased renal CCL5, treatment did not affect a panel of gene expression endpoints reflecting early fibrotic changes, inflammation and kidney injury. Finally, abatacept treatment effectively reduced the accumulation of activated CD4+ T cells in the kidney, suggesting that renal T cell inflammation is not a driving factor in the pathology of the STZ model. In conjunction with the recent data discounting the expression of B7-1 on podocytes, our present data do not support a role for abatacept in DN treatment.

Kidney (Renal Cell) Cancer—Health Professional Version

Science.gov (United States)

Kidney cancer has three main types. Renal cell cancer, or renal cell adenocarcinoma, forms in the tubules of the kidney. Transitional cell carcinoma forms in the renal pelvis and ureter. Wilms tumors are common in children. Find evidence-based information on kidney cancer treatment, research, genetics, and statistics.

Characterization of renin mRNA expression and enzyme activity in rat and mouse mesangial cells

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Andrade A.Q.

2002-01-01

Full Text Available Renin is an enzyme involved in the stepwise generation of angiotensin II. Juxtaglomerular cells are the main source of plasma renin, but renin activity has been detected in other cell types. In the present study we evaluated the presence of renin mRNA in adult male Wistar rat and mouse (C-57 Black/6 mesangial cells (MC and their ability to process, store and release both the active and inactive forms of the enzyme. Active renin and total renin content obtained after trypsin treatment were estimated by angiotensinogen consumption analyzed by SDS-PAGE electrophoresis and quantified by angiotensin I generation by HPLC. Renin mRNA, detected by RT-PCR, was present in both rat and mouse MC under basal conditions. Active renin was significantly higher (P<0.05 in the cell lysate (43.5 ± 5.7 ng h-1 10(6 cells than in the culture medium (12.5 ± 2.5 ng h-1 10(6 cells. Inactive prorenin content was similar for the intra- and extracellular compartments (9.7 ± 3.1 and 3.9 ± 0.9 ng h-1 10(6 cells. Free active renin was the predominant form found in both cell compartments. These results indicate that MC in culture are able to synthesize and translate renin mRNA probably as inactive prorenin which is mostly processed to active renin inside the cell. MC secrete both forms of the enzyme but at a lower level compared with intracellular content, suggesting that the main role of renin synthesized by MC may be the intracellular generation of angiotensin II.

New strategy for renal fibrosis: Targeting Smad3 proteins for ubiquitination and degradation.

Science.gov (United States)

Wang, Xin; Feng, Shaozhen; Fan, Jinjin; Li, Xiaoyan; Wen, Qiong; Luo, Ning

2016-09-15

Smad3 is a critical signaling protein in renal fibrosis. Proteolysis targeting chimeric molecules (PROTACs) are small molecules designed to degrade target proteins via ubiquitination. They have three components: (1) a recognition motif for E3 ligase; (2) a linker; and (3) a ligand for the target protein. We aimed to design a new PROTAC to prevent renal fibrosis by targeting Smad3 proteins and using hydroxylated pentapeptide of hypoxia-inducible factor-1α as the recognition motif for von Hippel-Lindau (VHL) ubiquitin ligase (E3). Computer-aided drug design was used to find a specific ligand targeting Smad3. Surface plasmon resonance (SPR) was used to verify and optimize screening results. Synthesized PROTAC was validated by two-stage mass spectrometry. The PROTAC's specificity for VHL (E3 ligase) was proved with two human renal carcinoma cell lines, 786-0 (VHL(-)) and ACHN (VHL(+)), and its anti-fibrosis effect was tested in renal fibrosis cell models. Thirteen small molecular compounds (SMCs) were obtained from the Enamine library using GLIDE molecular docking program. SPR results showed that #8 SMC (EN300-72284) combined best with Smad3 (KD=4.547×10(-5)M). Mass spectrometry showed that synthesized PROTAC had the correct peptide molecular weights. Western blot showed Smad3 was degraded by PROTAC with whole-cell lysate of ACHN but not 786-0. Degradation, but not ubiquitination, of Smad3 was inhibited by proteasome inhibitor MG132. The upregulation of fibronectin and Collagen I induced by TGF-β1 in both renal fibroblast and mesangial cells were inhibited by PROTAC. The new PROTAC might prevent renal fibrosis by targeting Smad3 for ubiquitination and degradation. Copyright © 2016 Elsevier Inc. All rights reserved.

Epidermal growth factor receptor signaling mediates aldosterone-induced profibrotic responses in kidney

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Sheng, Lili; Yang, Min; Ding, Wei [Department of Nephrology, Shanghai Fifth People' s Hospital, Fudan University, Shanghai 200240 (China); Zhang, Minmin [Department of Nephrology, Shanghai Huashan Hospital, Fudan University, Shanghai 200240 (China); Niu, Jianying [Department of Nephrology, Shanghai Fifth People' s Hospital, Fudan University, Shanghai 200240 (China); Qiao, Zhongdong [School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240 (China); Gu, Yong, E-mail: yonggu@vip.163.com [Department of Nephrology, Shanghai Fifth People' s Hospital, Fudan University, Shanghai 200240 (China); Department of Nephrology, Shanghai Huashan Hospital, Fudan University, Shanghai 200240 (China)

2016-08-01

Aldosterone has been recognized as a risk factor for the development of chronic kidney disease (CKD). Studies have indicated that enhanced activation of epidermal growth factor receptor (EGFR) is associated with the development and progression of renal fibrosis. But if EGFR is involved in aldosterone-induced renal fibrosis is less investigated. In the present study, we examined the effect of erlotinib, an inhibitor of EGFR tyrosine kinase activity, on the progression of aldosterone-induced renal profibrotic responses in a murine model underwent uninephrectomy. Erlotinib-treated rats exhibited relieved structural lesion comparing with rats treated with aldosterone alone, as characterized by glomerular hypertrophy, mesangial cell proliferation and expansion. Also, erlotinib inhibited the expression of TGF-β, α-SMA and mesangial matrix proteins such as collagen Ⅳ and fibronectin. In cultured mesangial cells, inhibition of EGFR also abrogated aldosterone-induced expression of extracellular matrix proteins, cell proliferation and migration. We also demonstrated that aldosterone induced the phosphorylation of EGFR through generation of ROS. And the activation of EGFR resulted in the phosphorylation of ERK1/2, leading to the activation of profibrotic pathways. Taken together, we concluded that aldosterone-mediated tissue fibrosis relies on ROS induced EGFR/ERK activation, highlighting EGFR as a potential therapeutic target for modulating renal fibrosis. - Highlights: • EGFR was involved in aldosterone-induced renal profibrotic responses. • Aldosterone-induced EGFR activation was mediated by MR-dependent ROS generation. • EGFR activated the MAPK/ERK1/2 signaling to promote renal fibrosis.

Thrombin regulates components of the fibrinolytic system in human mesangial cells

International Nuclear Information System (INIS)

Villamediana, L.M.; Rondeau, E.; He, C.J.; Medcalf, R.L.; Peraldi, M.N.; Lacave, R.; Delarue, F.; Sraer, J.D.

1990-01-01

Besides its procoagulant activity, thrombin has been shown to stimulate cell proliferation and to regulate the fibrinolytic pathway. We report here the effect of purified human alpha thrombin on the synthesis of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) by cultured human mesangial cells. Thrombin (0 to 2.5 U/ml) increased in a time- and dose-dependent manner the production of t-PA and PAI-1 (2- to 3-fold increase of secreted t-PA and PAI-1 release during a 24 hour incubation). This effect was associated with a twofold increase in DNA synthesis measured by 3H-thymidine incorporation. Zymographic analysis and reverse fibrin autography showed that thrombin also increased the level of the 110 Kd t-PA-PAI-1 complex, whereas PAI-1 was present as a free 50 Kd form in the culture medium conditioned by unstimulated and thrombin-stimulated cells. Free t-PA was never observed. Both membrane binding and catalytic activity of thrombin were required since the effects of 1 U/ml thrombin were inhibited by addition 2 U/ml hirudin, which inhibits the membrane binding and catalytic activity of thrombin, and since DFP-inactivated thrombin, which has the ability to bind but which has no enzymatic activity, did not induce t-PA or PAI-1. Gamma thrombin, which does not bind to thrombin receptor, did not increase t-PA and PAI-1 releases. The effects of thrombin were probably mediated by protein kinase C activation since H7, an inhibitor of protein kinases, inhibited significantly thrombin effects on t-PA and PAI-1 production, and since addition of an activator of protein kinase A, 8-bromocyclic AMP (100 microM), induced a significant inhibition of the thrombin effect. The effects of thrombin were also suppressed by 1.25 micrograms/ml alpha amanitin, suggesting a requirement of de novo RNA synthesis

A bioartificial renal tubule device embedding human renal stem/progenitor cells.

Directory of Open Access Journals (Sweden)

Anna Giovanna Sciancalepore

Full Text Available We present a bio-inspired renal microdevice that resembles the in vivo structure of a kidney proximal tubule. For the first time, a population of tubular adult renal stem/progenitor cells (ARPCs was embedded into a microsystem to create a bioengineered renal tubule. These cells have both multipotent differentiation abilities and an extraordinary capacity for injured renal cell regeneration. Therefore, ARPCs may be considered a promising tool for promoting regenerative processes in the kidney to treat acute and chronic renal injury. Here ARPCs were grown to confluence and exposed to a laminar fluid shear stress into the chip, in order to induce a functional cell polarization. Exposing ARPCs to fluid shear stress in the chip led the aquaporin-2 transporter to localize at their apical region and the Na(+K(+ATPase pump at their basolateral portion, in contrast to statically cultured ARPCs. A recovery of urea and creatinine of (20±5% and (13±5%, respectively, was obtained by the device. The microengineered biochip here-proposed might be an innovative "lab-on-a-chip" platform to investigate in vitro ARPCs behaviour or to test drugs for therapeutic and toxicological responses.

Culture in embryonic kidney serum and xeno-free media as renal cell carcinoma and renal cell carcinoma cancer stem cells research model.

Science.gov (United States)

Krawczyk, Krzysztof M; Matak, Damian; Szymanski, Lukasz; Szczylik, Cezary; Porta, Camillo; Czarnecka, Anna M

2018-04-01

The use of fetal bovine serum hinders obtaining reproducible experimental results and should also be removed in hormone and growth factor studies. In particular hormones found in FBS act globally on cancer cell physiology and influence transcriptome and metabolome. The aim of our study was to develop a renal carcinoma serum free culture model optimized for (embryonal) renal cells in order to select the best study model for downstream auto-, para- or endocrine research. Secondary aim was to verify renal carcinoma stem cell culture for this application. In the study, we have cultured renal cell carcinoma primary tumour cell line (786-0) as well as human kidney cancer stem cells in standard 2D monolayer cultures in Roswell Park Memorial Institute Medium or Dulbecco's Modified Eagle's Medium and Complete Human Kidney Cancer Stem Cell Medium, respectively. Serum-free, animal-component free Human Embryonic Kidney 293 media were tested. Our results revealed that xeno-free embryonal renal cells optimized culture media provide a useful tool in RCC cancer biology research and at the same time enable effective growth of RCC. We propose bio-mimic RCC cell culture model with specific serum-free and xeno-free medium that promote RCC cell viability.

CD47 regulates renal tubular epithelial cell self-renewal and proliferation following renal ischemia reperfusion.

Science.gov (United States)

Rogers, Natasha M; Zhang, Zheng J; Wang, Jiao-Jing; Thomson, Angus W; Isenberg, Jeffrey S

2016-08-01

Defects in renal tubular epithelial cell repair contribute to renal ischemia reperfusion injury, cause acute kidney damage, and promote chronic renal disease. The matricellular protein thrombospondin-1 and its receptor CD47 are involved in experimental renal ischemia reperfusion injury, although the role of this interaction in renal recovery is unknown. We found upregulation of self-renewal genes (transcription factors Oct4, Sox2, Klf4 and cMyc) in the kidney of CD47(-/-) mice after ischemia reperfusion injury. Wild-type animals had minimal self-renewal gene expression, both before and after injury. Suggestive of cell autonomy, CD47(-/-) renal tubular epithelial cells were found to increase expression of the self-renewal genes. This correlated with enhanced proliferative capacity compared with cells from wild-type mice. Exogenous thrombospondin-1 inhibited self-renewal gene expression in renal tubular epithelial cells from wild-type but not CD47(-/-) mice, and this was associated with decreased proliferation. Treatment of renal tubular epithelial cells with a CD47 blocking antibody or CD47-targeting small interfering RNA increased expression of some self-renewal transcription factors and promoted cell proliferation. In a syngeneic kidney transplant model, treatment with a CD47 blocking antibody increased self-renewal transcription factor expression, decreased tissue damage, and improved renal function compared with that in control mice. Thus, thrombospondin-1 via CD47 inhibits renal tubular epithelial cell recovery after ischemia reperfusion injury through inhibition of proliferation/self-renewal. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Role of bone marrow-derived stem cells, renal progenitor cells and stem cell factor in chronic renal allograft nephropathy

Directory of Open Access Journals (Sweden)

Hayam Abdel Meguid El Aggan

2013-09-01

Full Text Available Introduction: Chronic allograft nephropathy (CAN is a poorly understood clinico-pathological entity associated with chronic allograft loss due to immunologic and non-immunologic causes. It remains the leading cause of late allograft loss. Bone marrow derived stem cells are undifferentiated cells typically characterized by their capacity for self renewal, ability to give rise to multiple differentiated cellular population, including hematopoietic (HSCs and mesenchymal stem cells (MSCs. Characterization of HSCs includes their multipotency, expression of typical surface markers such as CD34 and CD45, while characterization of MSC includes their multipotency, expression of typical surface markers such as CD90 and CD105, and the absence of hemopoietic lineage markers. Aim & methods: The aim of the present work was to study the role of bone marrow-derived HSCs and MSCs, renal progenitor cells and SCF in chronic renal allograft nephropathy in relation to renal hemodynamics and histopathological changes. We studied 30 patients with kidney transplantation for more than 6 months, divided into 15 patients with stable serum creatinine and 15 patients who developed CAN. Detection of HSCs and MSCs in the peripheral blood using flow cytometry via detection of CD34, CD45, CD117 and CD106, as well as immunohistochemical detection of CD34, CD133, VEGF and αSMA in transplanted kidney biopsies of patients with CAN were done. Results: There was a significant increase in the levels of SCF, number of peripheral blood HSCs and MSCs in both transplanted patient groups than the controls and they were higher in patients of group Ia than patients of group Ib, (F = 39.73, P < 0.001, (F = 13.28, P < 0.001, (F = 11.94, P < 0.001, respectively and this was accompanied by evident expression of markers of renal repair. Conclusion: Stem cells might have a role in renal regeneration in CAN and this may pave the way toward the use of stem cells in correction of CAN. KEYWORDS

Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

Science.gov (United States)

Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary

2016-01-01

Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169

Metastatic renal cell carcinoma management

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Flavio L. Heldwein

2009-06-01

Full Text Available PURPOSE: To assess the current treatment of metastatic renal cell carcinoma, focusing on medical treatment options. MATERIAL AND METHODS: The most important recent publications have been selected after a literature search employing PubMed using the search terms: advanced and metastatic renal cell carcinoma, anti-angiogenesis drugs and systemic therapy; also significant meeting abstracts were consulted. RESULTS: Progress in understanding the molecular basis of renal cell carcinoma, especially related to genetics and angiogenesis, has been achieved mainly through of the study of von Hippel-Lindau disease. A great variety of active agents have been developed and tested in metastatic renal cell carcinoma (mRCC patients. New specific molecular therapies in metastatic disease are discussed. Sunitinib, Sorafenib and Bevacizumab increase the progression-free survival when compared to therapy with cytokines. Temsirolimus increases overall survival in high-risk patients. Growth factors and regulatory enzymes, such as carbonic anhydrase IX may be targets for future therapies. CONCLUSIONS: A broader knowledge of clear cell carcinoma molecular biology has permitted the beginning of a new era in mRCC therapy. Benefits of these novel agents in terms of progression-free and overall survival have been observed in patients with mRCC, and, in many cases, have become the standard of care. Sunitinib is now considered the new reference first-line treatment for mRCC. Despite all the progress in recent years, complete responses are still very rare. Currently, many important issues regarding the use of these agents in the management of metastatic renal cancer still need to be properly addressed.

CT staging of renal cell carcinoma

International Nuclear Information System (INIS)

Spina, Juan C.; Garcia, Adriana T.; Rogondino, Jose; Spina, Juan C. h; Vidales, Valeria; Troiani, Guillermo; Iotti, Alejandro; Venditti, Julio

2002-01-01

Objective: To assess the usefulness of computerized tomography (CT) in the characterization of renal masses, in order to stage them, determine their prognosis and their appropriate clinical and/or surgical management. Material and Methods: Between 1988 and 2001, we selected 63 patients with renal tumors that had been examined by pathology. Patient's ages ranged from 16 to 88 years (25 women, 38 men). The studies were performed with a sequential helical CT, using 5 mm thickness sections every 5mm evaluating the cortico medullar and nephrographic phases. Renal tumors were characterized and staged without any knowledge about the pathological findings; subsequently the tomographic characteristics were compared to such findings. The following characteristics were evaluated: 1) mixed solid-cystic nature; 2) size; 3) borders; 4) enhancement; 5) necrosis; 6) hemorrhage; 7) central scar; 8) presence of fat; 9) collecting system; 10) capsular invasion; 11) perirenal fat invasion; 12) vessels; 13) Gerota's fascia; 14) lymph nodes; and 15) local and/or distant metastases. Results: Of the 63 tumors, 2 were complicated cysts; of the 61 remaining tumors, 10 were angiomyolipomas, 1 was a renal lymphoma, 1 was a focal xantogranulomatose pyelonephritis, 1 was a metanephric adenoma, 3 papillary renal cell carcinoma (RCC), 4 transitional cell tumors, 4 oncocytomas, 37 clear cell renal carcinoma. The CT could correctly characterize the 2 cystic tumors as such, as well as the 9 angiomyolipomas and the 4 transitional cell tumors. The 48 other tumors (1 angiomyolipoma, 1 lymphoma, 1 focal xantogranulomatose pyelonephritis, 1 metanephric adenoma, 3 papillary RCC, 4 oncocytomas, and 37 cell renal carcinomas) remaining were characterized as renal adenocarcinomas and CT staged. Conclusion: CT is a useful method to characterize renal masses since it determines their solid-cystic or fatty structure; aiding in many cases to define a surgical treatment. For the CT staging of renal tumors, the

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

Science.gov (United States)

Linehan, W Marston; Spellman, Paul T; Ricketts, Christopher J; Creighton, Chad J; Fei, Suzanne S; Davis, Caleb; Wheeler, David A; Murray, Bradley A; Schmidt, Laura; Vocke, Cathy D; Peto, Myron; Al Mamun, Abu Amar M; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W Kimryn; Brooks, Angela N; Hoadley, Katherine A; Robertson, A Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J; Bootwalla, Moiz; Baylin, Stephen B; Laird, Peter W; Cherniack, Andrew D; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B; Akbani, Rehan; Leiserson, Mark D M; Raphael, Benjamin J; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K; Czerniak, Bogdan; Godwin, Andrew K; Hakimi, A Ari; Ho, Thai H; Hsieh, James; Ittmann, Michael; Kim, William Y; Krishnan, Bhavani; Merino, Maria J; Mills Shaw, Kenna R; Reuter, Victor E; Reznik, Ed; Shelley, Carl S; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D; Penny, Robert J; Shelton, Candace; Shelton, W Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T; Bowen, Jay; Gastier-Foster, Julie M; Gerken, Mark; Leraas, Kristen M; Lichtenberg, Tara M; Ramirez, Nilsa C; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A; Felau, Ina; Hutter, Carolyn M; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C; Zhang, Jiashan; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S N; Carlsen, Rebecca; Carter, Scott L; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, Harsha V; Drummond, Jennifer A; Gabriel, Stacey B; Gibbs, Richard A; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D Neil; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven J M; Jones, Corbin D; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A; Moore, Richard A; Morton, Donna; Mose, Lisle E; Mungall, Andrew J; Muzny, Donna; Parker, Joel S; Perou, Charles M; Roach, Jeffrey; Schein, Jacqueline E; Schumacher, Steven E; Shi, Yan; Simons, Janae V; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L; Boice, Lori; Bollag, Roni J; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L; Slaton, Joel; Stanton, Melissa; Thompson, R Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M; Winemiller, Cynthia; Zach, Leigh Anne; Zuna, Rosemary

2016-01-14

Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

Triiodothyronine regulates cell growth and survival in renal cell cancer.

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Czarnecka, Anna M; Matak, Damian; Szymanski, Lukasz; Czarnecka, Karolina H; Lewicki, Slawomir; Zdanowski, Robert; Brzezianska-Lasota, Ewa; Szczylik, Cezary

2016-10-01

Triiodothyronine plays an important role in the regulation of kidney cell growth, differentiation and metabolism. Patients with renal cell cancer who develop hypothyreosis during tyrosine kinase inhibitor (TKI) treatment have statistically longer survival. In this study, we developed cell based model of triiodothyronine (T3) analysis in RCC and we show the different effects of T3 on renal cell cancer (RCC) cell growth response and expression of the thyroid hormone receptor in human renal cell cancer cell lines from primary and metastatic tumors along with human kidney cancer stem cells. Wild-type thyroid hormone receptor is ubiquitously expressed in human renal cancer cell lines, but normalized against healthy renal proximal tube cell expression its level is upregulated in Caki-2, RCC6, SKRC-42, SKRC-45 cell lines. On the contrary the mRNA level in the 769-P, ACHN, HKCSC, and HEK293 cells is significantly decreased. The TRβ protein was abundant in the cytoplasm of the 786-O, Caki-2, RCC6, and SKRC-45 cells and in the nucleus of SKRC-42, ACHN, 769-P and cancer stem cells. T3 has promoting effect on the cell proliferation of HKCSC, Caki-2, ASE, ACHN, SK-RC-42, SMKT-R2, Caki-1, 786-0, and SK-RC-45 cells. Tyrosine kinase inhibitor, sunitinib, directly inhibits proliferation of RCC cells, while thyroid hormone receptor antagonist 1-850 (CAS 251310‑57-3) has less significant inhibitory impact. T3 stimulation does not abrogate inhibitory effect of sunitinib. Renal cancer tumor cells hypostimulated with T3 may be more responsive to tyrosine kinase inhibition. Moreover, some tumors may be considered as T3-independent and present aggressive phenotype with thyroid hormone receptor activated independently from the ligand. On the contrary proliferation induced by deregulated VHL and or c-Met pathways may transgress normal T3 mediated regulation of the cell cycle.

How Kidney Cell Death Induces Renal Necroinflammation.

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Mulay, Shrikant R; Kumar, Santhosh V; Lech, Maciej; Desai, Jyaysi; Anders, Hans-Joachim

2016-05-01

The nephrons of the kidney are independent functional units harboring cells of a low turnover during homeostasis. As such, physiological renal cell death is a rather rare event and dead cells are flushed away rapidly with the urinary flow. Renal cell necrosis occurs in acute kidney injuries such as thrombotic microangiopathies, necrotizing glomerulonephritis, or tubular necrosis. All of these are associated with intense intrarenal inflammation, which contributes to further renal cell loss, an autoamplifying process referred to as necroinflammation. But how does renal cell necrosis trigger inflammation? Here, we discuss the role of danger-associated molecular patterns (DAMPs), mitochondrial (mito)-DAMPs, and alarmins, as well as their respective pattern recognition receptors. The capacity of DAMPs and alarmins to trigger cytokine and chemokine release initiates the recruitment of leukocytes into the kidney that further amplify necroinflammation. Infiltrating neutrophils often undergo neutrophil extracellular trap formation associated with neutrophil death or necroptosis, which implies a release of histones, which act not only as DAMPs but also elicit direct cytotoxic effects on renal cells, namely endothelial cells. Proinflammatory macrophages and eventually cytotoxic T cells further drive kidney cell death and inflammation. Dissecting the molecular mechanisms of necroinflammation may help to identify the best therapeutic targets to limit nephron loss in kidney injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Drugs Approved for Kidney (Renal Cell) Cancer

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... Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) Axitinib Bevacizumab Cabometyx ( ...

Metastatic Renal Cell Carcinoma to the Pancreas: A Review.

Science.gov (United States)

Cheng, Shaun Kian Hong; Chuah, Khoon Leong

2016-06-01

The pancreas is an unusual site for tumor metastasis, accounting for only 2% to 5% of all malignancies affecting the pancreas. The more common metastases affecting the pancreas include renal cell carcinomas, melanomas, colorectal carcinomas, breast carcinomas, and sarcomas. Although pancreatic involvement by nonrenal malignancies indicates widespread systemic disease, metastatic renal cell carcinoma to the pancreas often represents an isolated event and is thus amenable to surgical resection, which is associated with long-term survival. As such, it is important to accurately diagnose pancreatic involvement by metastatic renal cell carcinoma on histology, especially given that renal cell carcinoma metastasis may manifest more than a decade after its initial presentation and diagnosis. In this review, we discuss the clinicopathologic findings of isolated renal cell carcinoma metastases of the pancreas, with special emphasis on separating metastatic renal cell carcinoma and its various differential diagnoses in the pancreas.

RENAL MALIGNANT NEOPLASMS: RENAL CELL CARCINOMA

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Elisangela Giachini

2017-06-01

Full Text Available The aim of this study is to evaluate the incidence and prevalence of malignant kidney tumors, to contribute to identifying factors which the diagnosis of renal cell carcinomas. Through this study, we understand that kidney disease over the years had higher incidence rates, especially in adults in the sixth decade of life. The renal cell carcinoma (RCC is the third most common malignancy of the genitourinary tract, affecting 2% to 3% of the population. There are numerous ways of diagnosis; however, the most important are ultrasonography, magnetic resonance imaging and computed tomography. In general most of the patients affected by the CCR, have a good prognosis when diagnosed early and subjected to an effective treatment. This study conducted a literature review about the CCR, through this it was possible to understand the development needs of the imaging methods used for precise diagnosis and classification of RCC through the TNM system.

Engineering kidney cells: reprogramming and directed differentiation to renal tissues.

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Kaminski, Michael M; Tosic, Jelena; Pichler, Roman; Arnold, Sebastian J; Lienkamp, Soeren S

2017-07-01

Growing knowledge of how cell identity is determined at the molecular level has enabled the generation of diverse tissue types, including renal cells from pluripotent or somatic cells. Recently, several in vitro protocols involving either directed differentiation or transcription-factor-based reprogramming to kidney cells have been established. Embryonic stem cells or induced pluripotent stem cells can be guided towards a kidney fate by exposing them to combinations of growth factors or small molecules. Here, renal development is recapitulated in vitro resulting in kidney cells or organoids that show striking similarities to mammalian embryonic nephrons. In addition, culture conditions are also defined that allow the expansion of renal progenitor cells in vitro. Another route towards the generation of kidney cells is direct reprogramming. Key transcription factors are used to directly impose renal cell identity on somatic cells, thus circumventing the pluripotent stage. This complementary approach to stem-cell-based differentiation has been demonstrated to generate renal tubule cells and nephron progenitors. In-vitro-generated renal cells offer new opportunities for modelling inherited and acquired renal diseases on a patient-specific genetic background. These cells represent a potential source for developing novel models for kidney diseases, drug screening and nephrotoxicity testing and might represent the first steps towards kidney cell replacement therapies. In this review, we summarize current approaches for the generation of renal cells in vitro and discuss the advantages of each approach and their potential applications.

[Plasma cell dyscrasias and renal damage].

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Pasquali, Sonia; Iannuzzella, Francesco; Somenzi, Danio; Mattei, Silvia; Bovino, Achiropita; Corradini, Mattia

2012-01-01

Kidney damage caused by immunoglobulin free light chains in the setting of plasma cell dyscrasias is common and may involve all renal compartments, from the glomerulus to the tubulointerstitium, in a wide variety of histomorphological and clinical patterns. The knowledge of how free light chains can promote kidney injury is growing: they can cause functional changes, be processed and deposited, mediate inflammation, apoptosis and fibrosis, and obstruct nephrons. Each clone of the free light chain is unique and its primary structure and post-translation modification can determine the type of renal disease. Measurement of serum free light chain concentrations and calculation of the serum kappa/lambda ratio, together with renal biopsy, represent essential diagnostic tools. An early and correct diagnosis of renal lesions due to plasma cell dyscrasias will allow early initiation of disease-specific treatment strategies. The treatment of free light chain nephropathies is evolving and knowledge of the pathways that promote renal damage should lead to further therapeutic developments.

Epidemiologic characteristics and risk factors for renal cell cancer

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Loren Lipworth

2009-04-01

Full Text Available Loren Lipworth1,2, Robert E Tarone1,2, Lars Lund2,3, Joseph K McLaughlin1,21International Epidemiology Institute, Rockville, MD, USA; 2Department of Medicine (JKM, RET and Preventive Medicine (LL, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; 3Department of Urology, Viborg Hospital, Viborg, DenmarkAbstract: Incidence rates of renal cell cancer, which accounts for 85% of kidney cancers, have been rising in the United States and in most European countries for several decades. Family history is associated with a two- to four-fold increase in risk, but the major forms of inherited predisposition together account for less than 4% of renal cell cancers. Cigarette smoking, obesity, and hypertension are the most consistently established risk factors. Analgesics have not been convincingly linked with renal cell cancer risk. A reduced risk of renal cell cancer among statin users has been hypothesized but has not been adequately studied. A possible protective effect of fruit and vegetable consumption is the only moderately consistently reported dietary finding, and, with the exception of a positive association with parity, evidence for a role of hormonal or reproductive factors in the etiology of renal cell cancer in humans is limited. A recent hypothesis that moderate levels of alcohol consumption may be protective for renal cell cancer is not strongly supported by epidemiologic results, which are inconsistent with respect to the categories of alcohol consumption and the amount of alcohol intake reportedly associated with decreased risk. For occupational factors, the weight of the evidence does not provide consistent support for the hypotheses that renal cell cancer may be caused by asbestos, gasoline, or trichloroethylene exposure. The established determinants of renal cell cancer, cigarette smoking, obesity, and hypertension, account for less than half of these cancers. Novel epidemiologic approaches

Culture and Characterization of Circulating Endothelial Progenitor Cells in Patients with Renal Cell Carcinoma.

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Gu, Wenyu; Sun, Wei; Guo, Changcheng; Yan, Yang; Liu, Min; Yao, Xudong; Yang, Bin; Zheng, Junhua

2015-07-01

Although emerging evidence demonstrates increased circulating endothelial progenitor cells in patients with solid tumors, to our knowledge it is still unknown whether such cells can be cultured from patients with highly angiogenic renal cell carcinoma. We cultured and characterized circulating endothelial progenitor cells from patients with renal cell carcinoma. The circulating endothelial progenitor cell level (percent of CD45(-)CD34(+) VEGF-R2(+) cells in total peripheral blood mononuclear cells) was quantified in 47 patients with renal cell carcinoma and 40 healthy controls. Peripheral blood mononuclear cells were then isolated from 33 patients with renal cell carcinoma and 30 healthy controls to culture and characterize circulating endothelial progenitor cells. The circulating endothelial progenitor cell level was significantly higher in patients with renal cell carcinoma than in healthy controls (0.276% vs 0.086%, p cells first emerged significantly earlier in patient than in control preparations (6.72 vs 14.67 days, p culture success rate (87.8% vs 40.0% of participants) and the number of colonies (10.06 vs 1.83) were significantly greater for patients than for controls (each p cell level correlated positively with the number of patient colonies (r = 0.762, p Cells cultured from patients and controls showed a similar growth pattern, immunophenotype, ability to uptake Ac-LDL and bind lectin, and form capillary tubes in vitro. However, significantly more VEGF-R2(+) circulating endothelial progenitor cells were found in preparations from patients with renal cell carcinoma than from healthy controls (21.1% vs 13.4%, p cell colonies, a higher cell culture success rate and more colonies were found for patients with renal cell carcinoma than for healthy controls. Results indicate the important significance of VEGF-R2(+) circulating endothelial progenitors in patients with renal cell carcinoma. Copyright © 2015 American Urological Association Education and Research

Expression profiles of genes involved in xenobiotic metabolism and disposition in human renal tissues and renal cell models

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Van der Hauwaert, Cynthia; Savary, Grégoire [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Buob, David [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Leroy, Xavier; Aubert, Sébastien [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); Flamand, Vincent [Service d' Urologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Hennino, Marie-Flore [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Service de Néphrologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Perrais, Michaël [Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); and others

2014-09-15

Numerous xenobiotics have been shown to be harmful for the kidney. Thus, to improve our knowledge of the cellular processing of these nephrotoxic compounds, we evaluated, by real-time PCR, the mRNA expression level of 377 genes encoding xenobiotic-metabolizing enzymes (XMEs), transporters, as well as nuclear receptors and transcription factors that coordinate their expression in eight normal human renal cortical tissues. Additionally, since several renal in vitro models are commonly used in pharmacological and toxicological studies, we investigated their metabolic capacities and compared them with those of renal tissues. The same set of genes was thus investigated in HEK293 and HK2 immortalized cell lines in commercial primary cultures of epithelial renal cells and in proximal tubular cell primary cultures. Altogether, our data offers a comprehensive description of kidney ability to process xenobiotics. Moreover, by hierarchical clustering, we observed large variations in gene expression profiles between renal cell lines and renal tissues. Primary cultures of proximal tubular epithelial cells exhibited the highest similarities with renal tissue in terms of transcript profiling. Moreover, compared to other renal cell models, Tacrolimus dose dependent toxic effects were lower in proximal tubular cell primary cultures that display the highest metabolism and disposition capacity. Therefore, primary cultures appear to be the most relevant in vitro model for investigating the metabolism and bioactivation of nephrotoxic compounds and for toxicological and pharmacological studies. - Highlights: • Renal proximal tubular (PT) cells are highly sensitive to xenobiotics. • Expression of genes involved in xenobiotic disposition was measured. • PT cells exhibited the highest similarities with renal tissue.

N-domain angiotensin-I converting enzyme is expressed in immortalized mesangial, proximal tubule and collecting duct cells.

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Mei Wang, Pamella Huey; Andrade, Maria Claudina; Quinto, Beata Marie Redublo; Di Marco, Giovana; Mortara, Renato Arruda; Vio, Carlos P; Casarini, Dulce Elena

2015-01-01

Somatic ACE (sACE) is found in glomerulus, proximal tubule and excreted in urine. We hypothesized that N-domain ACE can also be found at these sites. ACE profile was analyzed in mesangial (IMC), proximal (LLC-PK1), distal tubule (MDCK) and collecting duct (IMCD) cells. Cell lysate and culture medium were submitted to gel filtration chromatography, which separated two peaks with ACE activity from cells and medium, except from distal tubule. The first had a high molecular weight and the second, a lower one (65 kDa; N-domain ACE). We focused on N-domain ACE purification and characterization from LLC-PK1. Total LLC-PK1 N-domain ACE purification was achieved by ion-exchange chromatography, which presented only one peak with ACE activity, denominated ACE(int2A). ACE(int2A) activity was influenced by pH, NaCl and temperature. The purified enzyme was inhibited by Captopril and hydrolyzed AngI, Ang1-7 and AcSDKP. Its ability to hydrolyze AcSDKP characterized it as an N-domain ACE. ACE(int2A) also presented high amino acid sequence homology with the N-terminal part of sACE from mouse, rat, human and rabbit. The presence of secreted and intracellular N-domain ACE and sACE in IMC, LLC-PK1 and IMCD cells confirmed our studies along the nephron. We identified, purified and characterized N-domain ACE from LLC-PK1. Copyright © 2014 Elsevier B.V. All rights reserved.

Relationship between histopathological changes in post partum renal biopsies and renal function tests of African women with early onset pre-eclampsia.

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Khedun, S M; Naicker, T; Moodley, J

2000-05-01

To improve the diagnostic accuracy of concurrent renal disease in hypertension of pregnancy, biopsy evaluation is essential. In addition, establishing underlying renal disease is important for prognosis on future pregnancies. We therefore designed a study to determine the diagnostic yield of postpartum renal biopsy and the nature and frequency of complications associated with this procedure. Also, to determine relationships, if any, between renal function tests and ultrastructural and histopathological findings. Fifty renal biopsies were performed in the immediate postpartum period in black African women with early onset pre-eclampsia. Each biopsy specimen was placed in a separate container and coded so that sampling was unknown to the electron microscopist. Each biopsy specimen was divided into three parts, and processed and stained for light, fluorescent and transmission electron microscopy using conventional techniques. Renal tissue biopsies were adequate for diagnostic purposes in all cases. There were no complications in any of the 50 patients studied. Ultrastructural examination confirmed the light microscopy findings. In addition the ultrastructural findings showed intramembranous deposits, foot process fusion and mesangial deposits. In 16 patients with normal renal function tests; the biopsies evaluation from these patients showed ultrastructural changes. In the remaining 34 patients with abnormal renal function tests of varying severity; biopsy evaluation from these patients showed both ultrastructural and histopathological changes. Renal biopsy procedure is safe, and ultrastructural and histological findings obtained from postpartum renal biopsies are more informative than the routine renal function tests.

The relationship of mast cells and angiogenesis with prognosis in renal cell carcinoma

International Nuclear Information System (INIS)

Guldur, M.E.; Kocarslan, S.; Dincoglu, D.

2014-01-01

Objective: To evaluate the effects of mast cell count and angiogenesis on the prognosis of renal cell carcinoma. Methods: The retrospective study was conducted at the Harran University, Sanliurfa, Turkey, and included 64 cases with diagnosis of renal cell carcinoma between 2002 and 2012. Immunohistochemical analysis was performed on paraffin sections using the standard streptavidin-biotin immunoperoxidase method. CD31 antibodies were used to identify microvessels in tumoural tissues. The microvessel density was calculated using a serological method. The mean vascular density was equivalent to the vascular surface area (in mm) per unit tissue volume (in mm) (MVD=mm). Mast cells tryptase antibody was used to evaluate the mast cell count in tumoural and non-tumoural tissues. The relationship between mast cell count and microvessel density was evaluated and compared with stage, grade, tumour diameter, and age. Results: The mast cell count in the tumoral tissue of renal cell carcinoma was significantly higher compared with non-neoplastic renal tissue (p 0.05). The intratumoural mast cell count in clear cell renal carcinoma was significantly higher compared with non-clear variety (p=0.001). No significant relationship was found between microvessel density, age, stage, diameter, or grade of the tumour and tumoral mast cell count (p>0.05). Conclusion: No significant association was found between the number of mast cells in tumoral tissue and microvessel density. Further studies are needed to demonstrate the effect of mast cells on angiogenesis in renal cell carcinoma. (author)

Nephrotic syndrome in primary myelofibrosis with renal extramedullary hematopoiesis and glomerulopathy in the JAK inhibitor era.

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Del Sordo, Rachele; Brugnano, Rachele; Covarelli, Carla; Fiorucci, Gioia; Falzetti, Franca; Barbatelli, Giorgio; Nunzi, Emidio; Sidoni, Angelo

2017-01-01

Primary myelofibrosis (PMF) is an uncommon form of myeloproliferative neoplasm (MPN) characterized by a proliferation of predominantly megakaryocytes and granulocytes in the bone marrow that, in fully-developed disease, is associated with reactive deposition of fibrous connective tissue, extramedullary hematopoiesis (EMH), and splenomegaly. Kidney involvement is rare and clinically presents with proteinuria, nephrotic syndrome, and renal insufficiency. Renal damage can be due to EMH and glomerulopathy. Renal EMH presents three patterns: infiltration of the interstitium with possible renal failure caused by functional damage of parenchyma and vessels, infiltration of capsule and pericapsular adipose tissue, and sclerosing mass-like lesions that can cause hydronephrosis and hydroureter with obstructive uropathy and renal failure. Glomerulopathy associated with PMF is rarely described, ranging from 1 month to 18 years from diagnosis of the neoplasm to renal biopsy. It is characterized by expansion and hypercellularity mesangial, segmental sclerosis, features of chronic thrombotic microangiopathy (TMA), and intracapillary hematopoietic cells infiltrating in absence of immune-mediated glomerulonephritis. We present a nephrotic syndrome in PMF-related glomerulopathy, associated with EMH, without renal failure, in a patient under treatment for 2 years with JAK2 inhibitor ruxolitinib. Despite treatment, the patient died 7 months after renal biopsy. Nephrologists still know very little about this topic and there is no homogeneous data about incidence, pathogenesis, and optimal treatment of this poor prognostic PMF-associated nephrotic syndrome. We focus on data in the literature in the hope of stimulating hematologists, nephrologists, pathologists to future studies about the natural history of renal involvement, useful for optimal management of this rare pathology.

Asymptomatic renal cell carcinoma incidentally detected by abdominal CT

International Nuclear Information System (INIS)

Yoneda, Fumio; Miyake, Noriaki; Tsujimura, Haruhiro; Nakajima, Mikio; Akiyama, Hajime

1987-01-01

Four cases of renal cell carcinoma that were incidentally detected by abdominal CT are reported. Abdominal CT was performed during gastro-intestinal examination in two patients and for suspected liver disease in the other two. No patient had symptoms of renal cell carcinoma, or hematuria. In all cases, the histopathological diagnosis was renal cell carcinoma of a low stage. (author)

Renal Protective Effect of Xiao-Chai-Hu-Tang on Diabetic Nephropathy of Type 1-Diabetic Mice

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Chun-Ching Lin

2012-01-01

Full Text Available Xiao-Chai-Hu-Tang (XCHT, a traditional Chinese medicine formula consisting of seven medicinal plants, is used in the treatment of various diseases. We show here that XCHT could protect type-1 diabetic mice against diabetic nephropathy, using streptozotocin (STZ-induced diabetic mice and high-glucose (HG-exposed rat mesangial cell (RMC as models. Following 4 weeks of oral administration with XCHT, renal functions and renal hypertrophy significantly improved in the STZ-diabetic mice, while serum glucose was only moderately reduced compared to vehicle treatment. Treatment with XCHT in the STZ-diabetic mice and HG-exposed RMC resulted in a decrease in expression levels of TGF-β1, fibronectin, and collagen IV, with concomitant increase in BMP-7 expression. Data from DPPH assay, DHE stain, and CM-H2DCFDA analysis indicated that XCHT could scavenge free radicals and inhibit high-glucose-induced ROS in RMCs. Taken together, these results suggest that treatment with XCHT can improve renal functions in STZ-diabetic mice, an effect that is potentially mediated through decreasing oxidative stress and production of TGF-β1, fibronectin, and collagen IV in the kidney during development of diabetic nephropathy. XCHT, therefore merits further investigation for application to improve renal functions in diabetic disorders.

Simultaneous Infiltration of Polyfunctional Effector and Suppressor T Cells into Renal Cell Carcinomas

NARCIS (Netherlands)

Attig, Sebastian; Hennenlotter, Jörg; Pawelec, Graham; Klein, Gerd; Koch, Sven D.; Pircher, Hanspeter; Feyerabend, Susan; Wernet, Dorothee; Stenzl, Arnulf; Rammensee, Hans-Georg; Gouttefangeas, Cécile

2009-01-01

Renal cell carcinoma is frequently infiltrated by cells of the immune system. This makes it important to understand interactions between cancer cells and immune cells so they can be manipulated to bring clinical benefit. Here, we analyze subsets and functions of T lymphocytes infiltrating renal cell

Vorapaxar treatment reduces mesangial expansion in streptozotocin-induced diabetic nephropathy in mice.

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Waasdorp, Maaike; Duitman, JanWillem; Florquin, Sandrine; Spek, C Arnold

2018-04-24

Twenty years after the onset of diabetes, up to 40% of patients develop diabetic nephropathy. Protease-activated receptor-1 (PAR-1) has recently been shown to aggravate the development of experimental diabetic nephropathy. PAR-1 deficient mice develop less albuminuria and glomerular lesions and PAR-1 stimulation induces proliferation and fibronectin production in mesangial cells in vitro . Vorapaxar is a clinically available PAR-1 inhibitor which is currently used for secondary prevention of ischemic events. The aim of this study was to investigate in a preclinical setting whether vorapaxar treatment may be a novel strategy to reduce diabetes-induced kidney damage. While control treated diabetic mice developed significant albuminuria, mesangial expansion and glomerular fibronectin deposition, diabetic mice on vorapaxar treatment did not show any signs of kidney damage despite having similar levels of hyperglycemia. These data show that PAR-1 inhibition by vorapaxar prevents the development of diabetic nephropathy in this preclinical animal model for type I diabetes and pinpoint PAR-1 as a novel therapeutic target to pursue in the setting of diabetic nephropathy. 22 C57Bl/6 mice were made diabetic using multiple low-dose streptozotocin injections (50 mg/kg) and 22 littermates served as non-diabetic controls. Four weeks after the induction of diabetes, 11 mice of each group were assigned to control or vorapaxar treatment. Mice were sacrificed after 20 weeks of treatment and kidney damage was evaluated.

Renal stem cells: fact or science fiction?

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McCampbell, Kristen K; Wingert, Rebecca A

2012-06-01

The kidney is widely regarded as an organ without regenerative abilities. However, in recent years this dogma has been challenged on the basis of observations of kidney recovery following acute injury, and the identification of renal populations that demonstrate stem cell characteristics in various species. It is currently speculated that the human kidney can regenerate in some contexts, but the mechanisms of renal regeneration remain poorly understood. Numerous controversies surround the potency, behaviour and origins of the cell types that are proposed to perform kidney regeneration. The present review explores the current understanding of renal stem cells and kidney regeneration events, and examines the future challenges in using these insights to create new clinical treatments for kidney disease.

Renal epithelioid angiomyolipoma presenting clinically as renal cell ...

African Journals Online (AJOL)

M.S. Johnson

a Detroit Medical Center, Michigan State University School of Osteopathic Medicine, Detroit, MI, USA .... Immunohistochemically, the tumor cells stained strongly positive .... [10] Cao Q, Liu F, Xiao P, Tian X, Li B, Li Z. Coexistence of renal.

Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure.

Science.gov (United States)

Baba, Asuka; Tachi, Masahiro; Ejima, Yutaka; Endo, Yasuhiro; Toyama, Hiroaki; Saito, Kazutomo; Abe, Nozomu; Yamauchi, Masanori; Miura, Chieko; Kazama, Itsuro

2017-02-01

Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF. © 2016 Asian Pacific Society of Nephrology.

Metastatic renal cell carcinoma in the nasopharynx.

Science.gov (United States)

Atar, Yavuz; Topaloglu, Ilhan; Ozcan, Deniz

2013-01-01

Metastatic renal cell carcinoma of the nasopharynx, nasal cavity, and paranasal sinuses can be misdiagnosed as primary malignant or benign diseases. A 33-year-old male attended our outpatient clinic complaining of difficulty breathing through the nose, bloody nasal discharge, postnasal drop, snoring, and discharge of phlegm. Endoscopic nasopharyngeal examination showed a vascularized nasopharyngeal mass. Under general anesthesia, multiple punch biopsies were taken from the nasopharynx. Pathologically, the tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. After the initial pathological examination, the pathologist requested more information about the patient's clinical status. A careful history revealed that the patient had undergone left a nephrectomy for a kidney mass diagnosed as renal cell carcinoma 3 years earlier. Subsequently, nasopharyngeal metastatic renal cell carcinoma was diagnosed by immunohistochemical staining with CD10 and vimentin. Radiotherapy was recommended for treatment.

Metastatic renal cell carcinoma in the nasopharynx

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Yavuz Atar

2013-01-01

Full Text Available Metastatic renal cell carcinoma of the nasopharynx, nasal cavity, and paranasal sinuses can be misdiagnosed as primary malignant or benign diseases. A 33-year-old male attended our outpatient clinic complaining of difficulty breathing through the nose, bloody nasal discharge, postnasal drop, snoring, and discharge of phlegm. Endoscopic nasopharyngeal examination showed a vascularized nasopharyngeal mass. Under general anesthesia, multiple punch biopsies were taken from the nasopharynx. Pathologically, the tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. After the initial pathological examination, the pathologist requested more information about the patient′s clinical status. A careful history revealed that the patient had undergone left a nephrectomy for a kidney mass diagnosed as renal cell carcinoma 3 years earlier. Subsequently, nasopharyngeal metastatic renal cell carcinoma was diagnosed by immunohistochemical staining with CD10 and vimentin. Radiotherapy was recommended for treatment.

Modulation of the TGFβ/Smad signaling pathway in mesangial cells by CTGF/CCN2

International Nuclear Information System (INIS)

Abdel Wahab, Nadia; Weston, Benjamin S.; Mason, Roger M.

2005-01-01

Transforming growth factor-beta (TGFβ) drives fibrosis in diseases such as diabetic nephropathy (DN). Connective tissue growth factor (CTGF; CCN2) has also been implicated in this, but the molecular mechanism is unknown. We show that CTGF enhances the TGFβ/Smad signaling pathway by transcriptional suppression of Smad 7 following rapid and sustained induction of the transcription factor TIEG-1. Smad 7 is a known antagonist of TGFβ signaling and TIEG-1 is a known repressor of Smad 7 transcription. CTGF enhanced TGFβ-induced phosphorylation and nuclear translocation of Smad 2 and Smad 3 in mesangial cells. Antisense oligonucleotides directed against TIEG-1 prevented CTGF-induced downregulation of Smad 7. CTGF enhanced TGFβ-stimulated transcription of the SBE4-Luc reporter gene and this was markedly reduced by TIEG-1 antisense oligonucleotides. Expression of the TGFβ-responsive genes PAI-1 and Col III over 48 h was maximally stimulated by TGFβ + CTGF compared to TGFβ alone, while CTGF alone had no significant effect. TGFβ-stimulated expression of these genes was markedly reduced by both CTGF and TIEG-1 antisense oligonucleotides, consistent with the endogenous induction of CTGF by TGFβ. We propose that under pathological conditions, where CTGF expression is elevated, CTGF blocks the negative feedback loop provided by Smad 7, allowing continued activation of the TGFβ signaling pathway

Specific drug delivery to the kidney

NARCIS (Netherlands)

Haas, M; Moolenaar, F; Meijer, DKF; de Zeeuw, D

2002-01-01

The mesangial cells of the glomerulus, the proximal tubular cells and the interstitial fibroblasts are the first choice targets for renal drug delivery since they play a pivotal role in many disease processes in the kidney. In the present review, only targeting to the proximal tubular cell is

Severe paraneoplastic hypereosinophilia in metastatic renal cell carcinoma

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Todenhöfer Tilman

2012-03-01

Full Text Available Abstract Background Renal cell carcinoma can cause various paraneoplastic syndromes including metabolic and hematologic disturbances. Paraneoplastic hypereosinophilia has been reported in a variety of hematologic and solid tumors. We present the first case in the literature of severe paraneoplastic hypereosinophilia in a patient with renal cell carcinoma. Case presentation A 46 year-old patient patient with a history of significant weight loss, reduced general state of health and coughing underwent radical nephrectomy for metastasized renal cell carcinoma. Three weeks after surgery, the patient presented with excessive peripheral hypereosinophilia leading to profound neurological symptoms due to cerebral microinfarction. Systemic treatment with prednisolone, hydroxyurea, vincristine, cytarabine, temsirolimus and sunitinib led to reduction of peripheral eosinophils but could not prevent rapid disease progression of the patient. At time of severe leukocytosis, a considerable increase of cytokines associated with hypereosinophilia was measurable. Conclusions Paraneoplastic hypereosinophilia in patients with renal cell carcinoma might indicate poor prognosis and rapid disease progression. Myelosuppressive therapy is required in symptomatic patients.

Role of Bone Morphogenetic Proteins-7 (BMP-7 in the Renal Improvement Effect of DangGui (Angelica sinensis in Type-1 Diabetic Rats

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Ching-Hua Yeh

2011-01-01

Full Text Available Hyperglycemia induced reactive oxygen species (ROS generation is believed as major factors leading to diabetic nephropathy (DN. DangGui (Angelica sinensis is mentioned to show renal protective effect in combination with other herbs. Bone morphogenetic proteins-7 (BMP-7 is produced merit in protection of DN. The role of BMP-7 in DangGui-induced renal improvement is not clear. The present study investigated the effects of DangGui on renal functions, BMP-7 expression and the levels of ROS in streptozotocin (STZ-induced diabetic rats and high glucose-exposed rat mesangial cells (RMCs. After 1- or 4-week treatment, DangGui improved renal functions and increased renal BMP-7 expression in diabetic rats. The BMP-7 expression in RMCs was reduced by high glucose treatment and this could be reversed by DangGui. Moreover, RMCs exposed to high glucose were expired by BMP-7 RNAi transfection but those cells remained alive by scramble transfection. Thus, we employed regular RMCs to knock down BMP-7 with RNAi and we found that DangGui increased BMP-7 expression in these RMCs. Direct activation of BMP-7 expression by DangGui could be considered. The results of DPPH assay, DHE stain and lucigenin assay indicated that DangGui could inhibit high glucose-induced ROS in RMCs. These results suggest that DangGui has an ability to improve renal functions in STZ-diabetic rats through increasing endogenous BMP-7 expression and decreasing oxidative stress in kidney. The present study suggest that DangGui could be applied to improve renal functions in diabetic disorders.

Giant kidney worms in a patient with renal cell carcinoma.

Science.gov (United States)

Kuehn, Jemima; Lombardo, Lindsay; Janda, William M; Hollowell, Courtney M P

2016-03-07

Dioctophyma renale (D. renale), or giant kidney worms, are the largest nematodes that infect mammals. Approximately 20 cases of human infection have been reported. We present a case of a 71-year-old man with a recent history of unintentional weight loss and painless haematuria, passing elongated erythematous tissue via his urethra. CT revealed a left renal mass with pulmonary nodules and hepatic lesions. On microscopy, the erythematous tissue passed was identified as D. renale. On subsequent renal biopsy, pathology was consistent with renal cell carcinoma. This is the first reported case of concomitant D. renale infection and renal cell carcinoma, and the second reported case of D. renale infection of the left kidney alone. 2016 BMJ Publishing Group Ltd.

Genetics Home Reference: hereditary leiomyomatosis and renal cell cancer

Science.gov (United States)

... Home Health Conditions HLRCC Hereditary leiomyomatosis and renal cell cancer Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Hereditary leiomyomatosis and renal cell cancer ( HLRCC ) is a disorder in which affected individuals ...

Synchronous presentation of nasopharyngeal and renal cell carcinomas

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Cem Boruban

2006-06-01

Full Text Available We report a rare case of synchronous presentation of nasopharyngeal and renal cell carcinomas in a-50-year old male patient with long standing smoking history. The patient was initially presented with a diagnosis of nasopharyngeal carcinoma. During staging process, the abdominal computed tomography detected a right renal solid mass, 6.5 cm in diameter, originating from posterior portion of the right renal cortex. Right radical nephrectomy was performed and pathological examination revealed renal cell carcinoma. Smoking was thought to be a risk factor for both cancers. Systemic evaluation of kidney should not be discarded in patients diagnosed with nasopharyngeal carcinoma living in western countries with a smoking history.

Image-guided radiofrequency ablation of renal cell carcinoma

International Nuclear Information System (INIS)

Boss, Andreas; Clasen, Stephan; Pereira, Philippe L.; Kuczyk, Markus; Schick, Fritz

2007-01-01

The incidence of renal cell carcinoma is rising with the increased number of incidental detection of small tumours. During the past few years, percutaneous imaging-guided radiofrequency ablation has evolved as a minimally invasive treatment of small unresectable renal tumours offering reduced patient morbidity and overall health care costs. In radiofrequency ablation, thermal energy is deposited into a targeted tumour by means of a radiofrequency applicator. In recent studies, radiofrequency ablation was shown to be an effective and safe modality for local destruction of renal cell carcinoma. Radiofrequency applicator navigation can be performed via ultrasound, computed tomography or magnetic resonance guidance; however, ultrasound seems less favourable because of the absence of monitoring capabilities during ablation. On-line monitoring of treatment outcome can only be performed with magnetic resonance imaging giving the possibility of eventual applicator repositioning to ablate visible residual tumour tissue. Long-term follow-up is crucial to assess completeness of tumour ablation. New developments in ablation technology and radiological equipment will further increase the indication field for radiofrequency ablation of renal cell carcinoma. Altogether, radiofrequency ablation seems to be a promising new modality for the minimally invasive treatment of renal cell carcinoma, which was demonstrated to exhibit high short-term effectiveness. (orig.)

Inhibitory effects and mechanism of 25-OH-PPD on glomerular mesangial cell proliferation induced by high glucose.

Science.gov (United States)

Yu, Junxian; Liu, Chunna; Li, Zhe; Zhang, Chao; Wang, Zheng; Liu, Xinyu

2016-06-01

To investigate the protective effects and potential mechanism of the compound 25-OH-PPD (PPD) on the glomerular mesangial cells (GMC) under high glucose condition. The hypertrophic GMC cells were established by DMEM containing glucose and randomly divided into five groups, including the normal control group (Control), the high glucose model group (HG, 25 mmolL(-1)), the PPD low dose group (1μmolL(-1), PPD-L), the PPD middle dose group (5μmolL(-1), PPD -M) and the PPD high dose group (10μmolL(-1), UCN-H). The GMC were incubated for 48h under different treatment factors. Total protein content was determined by Lowry method. The diameter of the single GMC and volume were measured by computer photograph analysis system. The GMC cell viability was analyzed by MTT assay. The level of malondialdehyde (MDA), the content of glutathione (GSH) and superoxide dismutase (SOD) activity were measured by ELISA. [Ca(2+)]і transient was measured by Till image system and by cell-loading Fura-2/AM. The expression of COX-1 and COX-2 were also determined using ELISA method. The viability of GMC and the total protein content were decreased in HG group, different dosage PPD group could increase these indexes (PPPD could reduce the MDA and enhance GSH and SOD (PPPD-L, PPD-M or PPD-H), the [Ca(2+)]і transient was reduced (PPPD groups. The protective effects of PPD on GMC from HG-induced hypertrophy may be associated with the inhibition of [Ca(2+)]і transient and decreasing expression of COX-1 via the oxidative-stress injure pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

Hematopoietic stem cell mobilization therapy accelerates recovery of renal function independent of stem cell contribution

NARCIS (Netherlands)

Stokman, Geurt; Leemans, Jaklien C.; Claessen, Nike; Weening, Jan J.; Florquin, Sandrine

2005-01-01

Acute renal failure and tubular cell loss as a result of ischemia constitute major challenges in renal pathophysiology. Increasing evidence suggests important roles for bone marrow stem cells in the regeneration of renal tissue after injury. This study investigated whether the enhanced availability

Renal Sinus Fat Invasion and Tumoral Thrombosis of the Inferior Vena Cava-Renal Vein: Only Confined to Renal Cell Carcinoma

OpenAIRE

Turker Acar; Mustafa Harman; Serkan Guneyli; Sait Sen; Nevra Elmas

2014-01-01

Epithelioid angiomyolipoma (E-AML), accounting for 8% of renal angiomyolipoma, is usually associated with tuberous sclerosis (TS) and demonstrates aggressive behavior. E-AML is macroscopically seen as a large infiltrative necrotic tumor with occasional extension into renal vein and/or inferior vena cava. However, without history of TS, renal sinus and venous invasion E-AML would be a challenging diagnosis, which may lead radiologists to misinterpret it as a renal cell carcinoma (RCC). In this...

Influence of Radix Astragali, Hirudo, Hirudin and their Compound Medicated Serum on the Growth Cycle and Apoptosis of Glomerular Mesangial Cell in Rats

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Xianzhi Ren

2014-06-01

Full Text Available Objective: To observe the effect of Radix Astragali (RA, hirudo, hirudin and their compound medicated serum on growth cycle and apoptosis of glomerular mesangial cells (GMCs in rats and their apoptotic morphology. Methods: The prepared cells were randomly divided into control group, hirudo group, hirudin group, RA group and compound group. Flow cytometer was used to detect the growth cycle and apoptosis of GMCs while Wright stain and microscope were applied for the observation of apoptotic cells. Results: RA, hirudo, hirudin and their compound medicated serum could maintain abundant GMCs in gap phase 0/1 (G0/G1 and improve apoptotic rate of GMCs, which had significant differences when compared with control group (P ＜ 0.01. Additionally, they could improve GMCs apoptosis, and differences were significant in hirudo and formula groups when compared with control group (P ＜ 0.01. Conclusion: Hirudo, hirudin, RA and their compound (containing hirudo and RA can effectively inhibit MC proliferation and promote GMCs apoptosis by stopping GMCs entering phase S of which the efficacy of compound is the best, followed by hirudo.

Hemodynamic and renal implications of sodium-glucose cotransporter- 2 inhibitors in type 2 diabetes mellitus.

Science.gov (United States)

Tejedor Jorge, Alberto

2016-11-01

In DM2, there is increased expression of the proximal glucose transporter SGLT2. The increased glucose reabsorption from the urine to the proximal tubule and subsequently to the bloodstream, has three direct effects on the prognosis of patients with DM2: a) it increases the daily glucose load by raising the renal threshold for glucose, thus augmenting requirements for oral antidiabetics and insulin. This progressive increase occurs throughout the course of the disease and in parallel with the increase in renal mass (renal hypertrophy); b) because of the greater glucose reabsorption, glycosuria is lower than the level corresponding to glycaemia, decreasing the stimulus on the tubuloglomerular feedback system of the distal nephron. As a result, the glomerular vasodilation caused by hyperglycaemia is not arrested, maintaining glomerular hyperfiltration, and c) the excess glucose transported to the proximal tubular cells modifies their redox status, increasing local production of glycosylating products and activating local production of proinflammatory and profibrotic proliferative mediators. These mediators are responsible for the direct free radical damage to proximal tubular cells, for increased SGLT2 expression, increased production of collagen IV and extracellular matrix, and activation of monocyte/macrophages able to cause endothelial injury. The use of SGLT2 inhibitors not only reduces the reabsorption of glucose from the glomerular filtrate back into the circulationthus improving metabolic control in diabetesbut also restores tubuloglomerular feedback by increasing glycosuria and distal urinary flow. However, the most notable effect is due to inhibition of glucose entry to the proximal tubular cells. Glycosuria is toxic to the kidney: it harms glucosetransporting cells, that is, the proximal cells, which contain SGLT2. In animal models, SGLT2 inhibition reduces local production of oxygen-free radicals, the formation of mesangial matrix and collagen IV

Aging-associated renal disease in mice is fructokinase dependent.

Science.gov (United States)

Roncal-Jimenez, Carlos A; Ishimoto, Takuji; Lanaspa, Miguel A; Milagres, Tamara; Hernando, Ana Andres; Jensen, Thomas; Miyazaki, Makoto; Doke, Tomohito; Hayasaki, Takahiro; Nakagawa, Takahiko; Marumaya, Shoichi; Long, David A; Garcia, Gabriela E; Kuwabara, Masanari; Sánchez-Lozada, Laura G; Kang, Duk-Hee; Johnson, Richard J

2016-10-01

Aging-associated kidney disease is usually considered a degenerative process associated with aging. Recently, it has been shown that animals can produce fructose endogenously, and that this can be a mechanism for causing kidney damage in diabetic nephropathy and in association with recurrent dehydration. We therefore hypothesized that low-level metabolism of endogenous fructose might play a role in aging-associated kidney disease. Wild-type and fructokinase knockout mice were fed a normal diet for 2 yr that had minimal (renal injury was amplified by provision of high-salt diet for 3 wk, as noted by the presence of glomerular hypertrophy, mesangial matrix expansion, and alpha smooth muscle actin expression, and with segmental thrombi. Fructokinase knockout mice were protected from renal injury both at baseline and after high salt intake (3 wk) compared with wild-type mice. This was associated with higher levels of active (phosphorylated serine 1177) endothelial nitric oxide synthase in their kidneys. These studies suggest that aging-associated renal disease might be due to activation of specific metabolic pathways that could theoretically be targeted therapeutically, and raise the hypothesis that aging-associated renal injury may represent a disease process as opposed to normal age-related degeneration.

Diagnosis of renal cell cancer by dynamic MRI

International Nuclear Information System (INIS)

Togami, Izumi; Kitagawa, Takahiro; Katoh, Katsuya

1992-01-01

Dynamic MRI was performed in 15 cases (16 lesions) of renal cell cancer. The enhanced pattern of the tumor was mainly evaluated and findings were compared with these of dynamic CT and renal angiography. Enhanced patterns on dynamic MRI and dynamic CT were similar, but each phase on dynamic MRI tended to be prolonged compared with dynamic CT. Many hypervascular tumors on renal angiography had prominent enhancement in an early phase on dynamic MRI, but there was no prominent enhancement in cases with tumor thrombi in the renal vein or IVC. All hypovascular tumors were enhanced to some degree without exception on dynamic MRI. Dynamic MRI is considered to be useful for the evaluation of the characterization, especially vascularity, of renal cell cancer, but we should pay attention to the differential diagnosis from other tumor in atypical cases because its enhanced patterns are various on dynamic MRI. (author)

Comparison of para-aminophenol cytotoxicity in rat renal epithelial cells and hepatocytes.

Science.gov (United States)

Li, Ying; Bentzley, Catherine M; Tarloff, Joan B

2005-04-01

Several chemicals, including para-aminophenol (PAP), produce kidney damage in the absence of hepatic damage. Selective nephrotoxicity may be related to the ability of the kidney to reabsorb filtered water, thereby raising the intraluminal concentration of toxicants and exposing tubular epithelial cells to higher concentrations than would be present in other tissues. The present experiments tested the hypothesis that hepatocytes and renal epithelial cells exposed to equivalent concentrations of PAP would be equally susceptible to toxicity. Hepatocytes and renal epithelial cells were prepared by collagenase digestion of tissues obtained from female Sprague-Dawley rats. Toxicity was monitored using trypan blue exclusion, oxygen consumption and ATP content. We measured the rate of PAP clearance and formation of PAP-glutathione conjugate by HPLC. We found that renal epithelial cells accumulated trypan blue and showed declines in oxygen consumption and ATP content at significantly lower concentrations of PAP and at earlier time points than hepatocytes. The half-life of PAP in hepatocyte incubations was significantly shorter (0.71+/-0.07 h) than in renal epithelial cell incubations (1.33+/-0.23 h), suggesting that renal epithelial cells were exposed to PAP for longer time periods than hepatocytes. Renal epithelial cells formed significantly less glutathione conjugates of PAP (PAP-SG) than did hepatocytes, consistent with less efficient detoxification of reactive PAP intermediates by renal epithelial cells. Finally, hepatocytes contained significant more reduced glutathione (NPSH) than did renal epithelial cells, possibly explaining the enhanced formation of PAP-SG by this cell population. In conclusion, our data indicates that renal epithelial cells are intrinsically more susceptible to PAP cytotoxicity than are hepatocytes. This enhanced cytotoxicity may be due to longer exposure to PAP and/or reduced detoxification of reactive intermediates due to lower concentrations

[Case report of rare co-occurrence of renal cell carcinoma and crossed renal dystopia (L-shaped kidney)].

Science.gov (United States)

Bakov, V N; Los, M S

2017-10-01

L-shaped kidney refers to a rare anomaly of the relative kidney positioning. Due to low prevalence, the literature on the co-occurrence of this anomaly with malignancy is lacking. And, if the diagnosis of a renal anomaly does not present difficulties, if a tumor is detected in such a kidney, even MSCT does not always help differentiate a pelvic tumor from a tumor of the renal parenchyma spreading to the pelvicalyceal system. This has important implications for choosing an appropriate surgical strategy. A feature of the presented clinical observation is the co-occurrence of the rare anomaly of kidney position and locally advanced renal cell carcinoma spreading to the renal pelvis. Due to the massive spread of the tumor, an organ-sparing surgery was not feasible. Due to the suspicion of tumor spread to the renal pelvis, the patient underwent nephrureterectomy of the L-shaped kidney. Introduction to renoprival state with transfer to chronic hemodialysis became the only option to maintain homeostasis and extend the patients life. Histological examination revealed clear cell renal cell carcinoma with invasion of the pelvis and renal capsule, with no clear demarcation between the fused kidneys.

Evaluation of morphologically unclassified renal cell carcinoma with electron microscopy and novel renal markers: implications for tumor reclassification.

Science.gov (United States)

Talento, Romualdo; Hewan-Lowe, Karlene; Yin, Ming

2013-02-01

Despite progress in the classification of renal cell carcinomas (RCC), a subset of these carcinomas remains unclassified (RCC-U). Patients with RCC-U usually present at a late stage and have a poor prognosis. Several studies have attempted to extract new classifications of newly recognized renal carcinomas from the group of RCC-U. However, to date, no studies in the literature have attempted to characterize the RCC-U with unrecognizable cell types beyond the morphologic evaluation on H&E-stained sections. The purpose of this study was to evaluate this group of RCC-U using electron microscopy and novel renal markers. Ten cases of such RCC-U were identified for this study. At the ultrastructural level, they did not show typical morphology that resembled any of the well-studied, recognizable subtypes of RCC. However, they did reveal features of renal tubular epithelial differentiation. The histologic, ultrastructural, and immunophenotypic features indicated that these tumors are poorly differentiated renal epithelial tumors, possibly derived from the proximal nephron, with an immunohistochemical profile similar to high-grade clear cell RCC. It is, therefore, proposed that this group of renal carcinomas be renamed "poorly differentiated renal cell carcinoma, not otherwise specified." The current study showed that PAX-8 and carbonic anhydrase IX are reliable markers for this novel group of renal carcinoma, and that electron microscopy is an important adjunct in the evaluation of new and unusual renal entities.

Clinical presentation of renal cell carcinoma

International Nuclear Information System (INIS)

Rehman, R.A.; Ashraf, S.; Jamil, N.

2015-01-01

Most common malignant tumour of the kidney is Renal Cell Carcinoma (RCC) and is known for its unpredictable clinical behaviour. Aetiology and risk factors are not completely understood. Extensive workup is being done in the understanding of the disease, especially to diagnose early and to treat promptly. The objective of this study was to determine the clinical presentation and pathological pattern of RCC. Methods: After approval from ethical committee a retrospective review of records was conducted extending from January 2012 to January 2014 to identify clinical characteristics of renal cell carcinomas. The study included all renal cancer patients presented to Sheikh Zayed Hospital Lahore with in this specified period. The data was retrieved regarding, history, physical examination and necessary investigations such as ultrasonography of abdomen and pelvis and CT scan of abdomen and pelvis. Results: There were total of 50 cases. The male to female ratio was 3:2. Mean age of patients were 52.38 (18-93) years old. Most common clinical presentation was gross haematuria(66%).The mean tumour size was 8.34 (3-24) cm. Tumour histology were clear cell (84%), papillary transitional cell carcinoma (12%) and oncosytoma contributed 4%. Conclusion: We observed that large number of the patients with RCC presented with haematuria and most of them were male. Common pathological type was clear cell carcinoma. (author)

[Valsartan inhibits angiotensin II-Notch signaling of mesangial cells induced by high glucose].

Science.gov (United States)

Yuan, Qin; Lyu, Chuan; Wu, Can; Lei, Sha; Shao, Ying; Wang, Qiuyue

2016-01-01

To explore the role of angiotensin II (Ang II)-Notch signaling in high glucose-induced secretion of extracellular matrix of rat mesangial cells (RMCs) and to further investigate the protective effect of valsartan (one of Ang II receptor blockers) on kidney. Subcultured RMCs were divided into groups as follows: normal glucose group (5.5 mmol/L glucose); high glucose group (30 mmol/L glucose); high concentration of mannitol as osmotic control group (5.5 mmol/L glucose and 24.5 mmol/L mannitol); normal glucose plus 1 μmol/L N-[N-(3, 5-difluorophenacetyl)-L-alanyl ]-S-phenylglycine t-butyl ester (DAPT) group; normal glucose plus (1, 5, 10) μmol/L valsartan group; high glucose plus 1 μmol/L DAPT group; high glucose plus (1, 5, 10) μmol/L valsartan group. Cells and supernatants were harvested after 12, 24 and 48 hours. Notch1 expression was examined by Western blotting. Secretion of transforming growth factor (TGF-β) and fibronectin (FN) were detected by ELISA. Compared to the normal glucose group, Notch1 expression was elevated in the high glucose group after 12 hours, and peaked at 24 hours. Besides, secretion of TGF-β and FN were much higher in the high glucose group than in the normal glucose group in a time-dependent manner. Compared to the untreated group, Notch1 expression decreased in a dose-dependent manner in the valsartan or DAPT treated group under high glucose after 24 hours. After pre-treatment by either valsartan or DAPT in the high glucose group, secretion of TGF-β and FN obviously decreased as compared to the untreated group. Hyperglycemia could stimulate activation of Notch signaling in cultured RMCs, which may increase secretion of downstream fibrotic factors such as TGF-β and FN. Valsartan may decrease the secretion of downstream FN in a dose-dependent manner via inhibiting AngII-Notch signaling.

Morphological and cytohistochemical evaluation of renal effects of cadmium-doped silica nanoparticles given intratracheally to rat

International Nuclear Information System (INIS)

Coccini, T; Roda, E; Manzo, L; Barni, S

2013-01-01

Renal morphological parameters were determined in rats intratracheally instilled with model cadmium-containing silica nanoparticles (Cd-SiNPs, 1mg/rat), also exploring whether their potential modifications would be associated with toxicogenomic changes. Cd-SiNP effects, evaluated 7 and 30 days post-exposure, were assessed by (i) histopathology (Haematoxylin/Eosin Staining), (ii) characterization of apoptotic features by TUNEL staining. Data were compared with those obtained by CdCl 2 (400μg/rat), SiNPs (600μg/rat), 0.1 ml saline. Area-specific cell apoptosis was observed in all treatment groups: cortex and inner medulla were the most affected regions. Apoptotic changes were apparent at 7 days post-exposure in both areas, and were still observable in inner medulla 30 days after treatment. Increase in apoptotic frequency was more pronounced in Cd-SiNP-treated animals compared to either CdCl 2 or SiNPs. Histological findings showed comparable alterations in the renal glomerular (cortex) architecture occurring in all treatment groups at both time-points considered. The glomeruli appeared often collapsed, showing condensed, packed mesangial and endothelial cells. Oedematous haemorrhagic glomeruli were also observed in Cd-SiNPs-treated animals. Bare SiNPs caused morphological and apoptotic changes without modifying the renal gene expression profile. These findings support the concept that multiple assays and an integrated testing strategy should be recommended to characterize toxicological responses to nanoparticles in mammalian systems.

Morphological and cytohistochemical evaluation of renal effects of cadmium-doped silica nanoparticles given intratracheally to rat

Science.gov (United States)

Coccini, T.; Roda, E.; Barni, S.; Manzo, L.

2013-04-01

Renal morphological parameters were determined in rats intratracheally instilled with model cadmium-containing silica nanoparticles (Cd-SiNPs, 1mg/rat), also exploring whether their potential modifications would be associated with toxicogenomic changes. Cd-SiNP effects, evaluated 7 and 30 days post-exposure, were assessed by (i) histopathology (Haematoxylin/Eosin Staining), (ii) characterization of apoptotic features by TUNEL staining. Data were compared with those obtained by CdCl2 (400μg/rat), SiNPs (600μg/rat), 0.1 ml saline. Area-specific cell apoptosis was observed in all treatment groups: cortex and inner medulla were the most affected regions. Apoptotic changes were apparent at 7 days post-exposure in both areas, and were still observable in inner medulla 30 days after treatment. Increase in apoptotic frequency was more pronounced in Cd-SiNP-treated animals compared to either CdCl2 or SiNPs. Histological findings showed comparable alterations in the renal glomerular (cortex) architecture occurring in all treatment groups at both time-points considered. The glomeruli appeared often collapsed, showing condensed, packed mesangial and endothelial cells. Oedematous haemorrhagic glomeruli were also observed in Cd-SiNPs-treated animals. Bare SiNPs caused morphological and apoptotic changes without modifying the renal gene expression profile. These findings support the concept that multiple assays and an integrated testing strategy should be recommended to characterize toxicological responses to nanoparticles in mammalian systems.

Renal cell apoptosis in human lupus nephritis: a histological study

DEFF Research Database (Denmark)

Faurschou, M; Penkowa, Milena; Andersen, C B

2009-01-01

Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney...

Low Protein Diet Inhibits Uric Acid Synthesis and Attenuates Renal Damage in Streptozotocin-Induced Diabetic Rats

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Jianmin Ran

2014-01-01

Full Text Available Aim. Several studies indicated that hyperuricemia may link to the worsening of diabetic nephropathy (DN. Meanwhile, low protein diet (LPD retards exacerbation of renal damage in chronic kidney disease. We then assessed whether LPD influences uric acid metabolism and benefits the progression of DN in streptozotocin- (STZ- induced diabetic rats. Methods. STZ-induced and control rats were both fed with LPD (5% and normal protein diet (18%, respectively, for 12 weeks. Vital signs, blood and urinary samples for UA metabolism were taken and analyzed every 3 weeks. Kidneys were removed at the end of the experiment. Results. Diabetic rats developed into constantly high levels of serum UA (SUA, creatinine (SCr and 24 h amounts of urinary albumin excretion (UAE, creatintine (UCr, urea nitrogen (UUN, and uric acid (UUA. LPD significantly decreased SUA, UAE, and blood glucose, yet left SCr, UCr, and UUN unchanged. A stepwise regression showed that high UUA is an independent risk factor for DN. LPD remarkably ameliorated degrees of enlarged glomeruli, proliferated mesangial cells, and hyaline-degenerated tubular epithelial cells in diabetic rats. Expression of TNF-α in tubulointerstitium significantly decreased in LPD-fed diabetic rats. Conclusion. LPD inhibits endogenous uric acid synthesis and might accordingly attenuate renal damage in STZ-induced diabetic rats.

Antiangiogenic treatment diminishes renal injury and dysfunction via regulation of local AKT in early experimental diabetes.

Science.gov (United States)

Bai, Xiaoyan; Li, Xiao; Tian, Jianwei; Zhou, Zhanmei

2014-01-01

In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser⁴⁷³-AKT, phosphorylated Thr³⁰⁸-AKT, nephrin, angiotensin II (Ang II), angiotensin type II receptor 1 (ATR1) were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr³⁰⁸-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr³⁰⁸-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr³⁰⁸-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr³⁰⁸-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr³⁰⁸-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the interstitial fibrosis

Antiangiogenic treatment diminishes renal injury and dysfunction via regulation of local AKT in early experimental diabetes.

Directory of Open Access Journals (Sweden)

Xiaoyan Bai

Full Text Available In view of increased vascular endothelial growth factor-A (VEGF-A expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM. In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser⁴⁷³-AKT, phosphorylated Thr³⁰⁸-AKT, nephrin, angiotensin II (Ang II, angiotensin type II receptor 1 (ATR1 were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR, Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr³⁰⁸-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr³⁰⁸-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr³⁰⁸-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr³⁰⁸-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr³⁰⁸-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the

Renal abscess in a child with sickle cell anemia

OpenAIRE

Taksande Amar; Vilhekar K

2009-01-01

Renal abscess is rare in children and the usual presenting features include fever, lumbar pain, abdominal pain and occasional flank mass. Renal ultrasonography facilitates an early diagnosis and helps in percutaneous drainage. We herewith report on a child with sickle cell anemia who developed a renal abscess.

Renal abscess in a child with sickle cell anemia.

Science.gov (United States)

Taksande, Amar M; Vilhekar, K Y

2009-03-01

Renal abscess is rare in children and the usual presenting features include fever, lumbar pain, abdominal pain and occasional flank mass. Renal ultrasonography facilitates an early diagnosis and helps in percutaneous drainage. We herewith report on a child with sickle cell anemia who developed a renal abscess.

Alteraciones renales en la drepanocitosis Renal disorders in sickle cell disease

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Aramís Núñez-Quintana

2011-06-01

Full Text Available La drepanocitosis está asociada con un amplio espectro de alteraciones renales que tienen su base en la falciformación de los eritrocitos en los vasos de la médula renal, que conduce a fenómenos de isquemia, microinfartos y anomalías de la función tubular. Se producen también alteraciones glomerulares funcionales reversibles de la autorregulación renal (hiperfiltración, que pueden conducir a cambios anatómicos irreversibles con glomeruloesclerosis segmentaria focal. Estas anomalías se expresan tempranamente como microalbuminuria, proteinuria y de forma mas tardía, como síndrome nefrótico e insuficiencia renal crónica. Medidas terapéuticas como el uso de inhibidores de la enzima convertidora de la angiotensina II, de los bloqueadores del receptor de la angiotensina II, asociados o no con la hidroxiurea, pueden prevenir o retardar el daño glomerular. En el presente trabajo se exponen de forma resumida aspectos relacionados con la fisiopatología del daño renal en la drepanocitosis y su tratamiento.Sickle cell disease is associated with a wide range of renal disorders resulting from the falciformation of erythrocytes in vessels of the renal medulla, leading to ischemia, microinfarctions and tubular function abnormalities. Reversible glomerular functional renal self-regulation disorders (hyperfiltration also occur, which may lead to irreversible anatomical changes with focal segmental glomerular sclerosis. These anomalies are expressed at an early stage as microalbuminuria and proteinuria, and at a later stage as nephrotic syndrome and chronic renal failure. Therapeutic measures such as the use of angiotensin-II converting enzyme inhibitors and angiotensin-II receptor blockers, associated or not with hydroxyurea, may either prevent or delay glomerular damage. The paper succinctly presents the physiopathology of renal damage in drepanocytosis and its treatment.

Renal cell carcinoma in childhood

International Nuclear Information System (INIS)

Zanier, J.F.C.; Ramos, C.O.P.; Pereira, A.A.

1990-01-01

The authors present five cases of renal cell carcinoma in children, describing its aspects on excretory urography, ultra-sonography and computerized tomography. The clinical, pathological and radiological features are compared with those of the literature. (author)

Proteasome Activators, PA28α and PA28β, Govern Development of Microvascular Injury in Diabetic Nephropathy and Retinopathy

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Saeed Yadranji Aghdam

2016-01-01

Full Text Available Diabetic nephropathy (DN and diabetic retinopathy (DR are major complications of type 1 and type 2 diabetes. DN and DR are mainly caused by injury to the perivascular supporting cells, the mesangial cells within the glomerulus, and the pericytes in the retina. The genes and molecular mechanisms predisposing retinal and glomerular pericytes to diabetic injury are poorly characterized. In this study, the genetic deletion of proteasome activator genes, PA28α and PA28β genes, protected the diabetic mice in the experimental STZ-induced diabetes model against renal injury and retinal microvascular injury and prolonged their survival compared with wild type STZ diabetic mice. The improved wellbeing and reduced renal damage was associated with diminished expression of Osteopontin (OPN and Monocyte Chemoattractant Protein-1 (MCP-1 in the glomeruli of STZ-injected PA28α/PA28β double knockout (Pa28αβDKO mice and also in cultured mesangial cells and retinal pericytes isolated from Pa28αβDKO mice that were grown in high glucose. The mesangial PA28-mediated expression of OPN under high glucose conditions was suppressed by peptides capable of inhibiting the binding of PA28 to the 20S proteasome. Collectively, our findings demonstrate that diabetic hyperglycemia promotes PA28-mediated alteration of proteasome activity in vulnerable perivascular cells resulting in microvascular injury and development of DN and DR.

Renal abscess in a child with sickle cell anemia

International Nuclear Information System (INIS)

Taksande, Amar M; Vilhekar, KY

2009-01-01

Renal abscess is rare in children and the usual presenting features include fever, lumbar pain, abdominal pain and occasional flank mass. Renal ultrasonography facilitates an early diagnosis and helps in percutaneous drainage. We herewith report on a child with sickle cell anemia who developed a renal abscess. (author)

Stem cell factor expression after renal ischemia promotes tubular epithelial survival.

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Geurt Stokman

Full Text Available BACKGROUND: Renal ischemia leads to apoptosis of tubular epithelial cells and results in decreased renal function. Tissue repair involves re-epithelialization of the tubular basement membrane. Survival of the tubular epithelium following ischemia is therefore important in the successful regeneration of renal tissue. The cytokine stem cell factor (SCF has been shown to protect the tubular epithelium against apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: In a mouse model for renal ischemia/reperfusion injury, we studied how expression of c-KIT on tubular epithelium and its ligand SCF protect cells against apoptosis. Administration of SCF specific antisense oligonucleotides significantly decreased specific staining of SCF following ischemia. Reduced SCF expression resulted in impaired renal function, increased tubular damage and increased tubular epithelial apoptosis, independent of inflammation. In an in vitro hypoxia model, stimulation of tubular epithelial cells with SCF activated survival signaling and decreased apoptosis. CONCLUSIONS/SIGNIFICANCE: Our data indicate an important role for c-KIT and SCF in mediating tubular epithelial cell survival via an autocrine pathway.

Kidney (Renal Cell) Cancer—Patient Version

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Kidney cancer can develop in adults and children. The main types of kidney cancer are renal cell cancer, transitional cell cancer, and Wilms tumor. Certain inherited conditions increase the risk of kidney cancer. Start here to find information on kidney cancer treatment, research, and statistics.

Magnetic resonance imaging of large chromophobe renal cell carcinomas

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Sasaguri, Kohei; Irie, Hiroyuki; Kamochi, Noriyuki; Nakazono, Takahiko; Yamaguchi, Ken; Uozumi, Jiro; Kudo, Sho

2010-01-01

The objective of this study was to clarify the magnetic resonance imaging (MRI) findings of large chromophobe renal cell carcinomas. Five patients diagnosed pathologically with chromophobe renal cell carcinoma are included. MRI findings were retrospectively evaluated for the tumor contour, uniformity and hypointensity of the rim of the tumor on T2-weighted images, ''micro-scopic fat'', enhancement degree and pattern on dynamic study, and necrosis in the tumor, among other findings. The tumor size ranged from 4.8 to 13.7 cm (mean 7.9 cm). The tumor contour was well defined in four patients. All but one tumor showed a hypointensity rim, and all tumors had a heterogeneous appearance on T2-weighted images. ''Microscopic fat'' was detected in one case. All tumors demonstrated low enhancement compared to that of the renal cortex. All tumors showed heterogeneous enhancement on postcontrast images. Necrosis was seen in four. Hemorrhage and renal vein thrombosis was seen in one. Chromophobe renal cell carcinomas of large size tend to have a heterogeneous appearance on post-contrast and T2-weighted images, a well-defined tumor contour with a hypointensity rim on T2-wighted images, and lower enhancement than that of the renal cortex. Tumor necrosis is easily apparent, and ''microscopic fat'' may be observed. (author)

Renal abscess in a child with sickle cell anemia

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Taksande Amar

2009-01-01

Full Text Available Renal abscess is rare in children and the usual presenting features include fever, lumbar pain, abdominal pain and occasional flank mass. Renal ultrasonography facilitates an early diagnosis and helps in percutaneous drainage. We herewith report on a child with sickle cell anemia who developed a renal abscess.

Segmental arterial mediolysis with mesangial cell hyperplasia

DEFF Research Database (Denmark)

Slavin, Richard E.; Leifsson, Páll Skúli

2017-01-01

doubt on this hypothesis. Methods and findings: SAM, reported in kidneys of slaughtered pigs, was believed to represent a dysfunctional development in a fight and flight response. Additionally some stenotic renal arteries described in cases of pheochromocytomas reportedly were caused by arterial spasm...... branches of the peripheral sympathetic nerves that innervate the large and medial sized muscular arteries targeted in SAM. Recognized stimuli for this response are iatrogenic sympathomimetic agonists and some B-2 agonists. However, these stimuli were not always apparent in published cases of SAM casting...

Outcome of Patients With Metastatic Sarcomatoid Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium

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Kyriakopoulos, Christos E; Chittoria, Namita; Choueiri, Toni K

2015-01-01

BACKGROUND: Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. PATIENTS AND METHODS: Clinical, prognostic, and treatment parameters in metastatic renal cell carcinoma patients with and without sarcomatoid histology......% intermediate risk, and 40% vs. 24% poor risk; P system metastases (6...... of second- (P = .018) and third-line (P systemic therapy. The median progression-free survival (PFS)/overall survival (OS) was 4.5/10.4 months in sRCC patients and 7.8/22.5 months in non-sRCC patients (P

Genetics of Kidney Cancer (Renal Cell Cancer) (PDQ®)—Health Professional Version

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Genetics of Kidney Cancer (Renal Cell) includes the hereditary cancer syndromes von Hippel-Lindau disease, hereditary leiomyomatosis and renal cell cancer, Birt-Hogg-Dubé syndrome, and hereditary papillary renal carcinoma. Get comprehensive information on these syndromes in this clinician summary.

Renal epithelial cells can release ATP by vesicular fusion

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Randi G Bjaelde

2013-09-01

Full Text Available Renal epithelial cells have the ability to release nucleotides as paracrine factors. In the intercalated cells of the collecting duct, ATP is released by connexin30 (cx30, which is selectively expressed in this cell type. However, ATP is released by virtually all renal epithelia and the aim of the present study was to identify possible alternative nucleotide release pathways in a renal epithelial cell model. We used MDCK (type1 cells to screen for various potential ATP release pathways. In these cells, inhibition of the vesicular H+-ATPases (bafilomycin reduced both the spontaneous and hypotonically (80%-induced nucleotide release. Interference with vesicular fusion using N-ethylamide markedly reduced the spontaneous nucleotide release, as did interference with trafficking from the endoplasmic reticulum to the Golgi apparatus (brefeldin A1 and vesicular transport (nocodazole. These findings were substantiated using a siRNA directed against SNAP-23, which significantly reduced spontaneous ATP release. Inhibition of pannexin and connexins did not affect the spontaneous ATP release in this cell type, which consists of ∼90% principal cells. TIRF-microscopy of either fluorescently-labeled ATP (MANT-ATP or quinacrine-loaded vesicles, revealed that spontaneous release of single vesicles could be promoted by either hypoosmolality (50% or ionomycin. This vesicular release decreased the overall cellular fluorescence by 5.8% and 7.6% respectively. In summary, this study supports the notion that spontaneous and induced ATP release can occur via exocytosis in renal epithelial cells.

Renal sinus fat invasion and tumoral thrombosis of the inferior vena cava-renal vein: only confined to renal cell carcinoma.

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Acar, Turker; Harman, Mustafa; Guneyli, Serkan; Sen, Sait; Elmas, Nevra

2014-01-01

Epithelioid angiomyolipoma (E-AML), accounting for 8% of renal angiomyolipoma, is usually associated with tuberous sclerosis (TS) and demonstrates aggressive behavior. E-AML is macroscopically seen as a large infiltrative necrotic tumor with occasional extension into renal vein and/or inferior vena cava. However, without history of TS, renal sinus and venous invasion E-AML would be a challenging diagnosis, which may lead radiologists to misinterpret it as a renal cell carcinoma (RCC). In this case presentation, we aimed to report cross-sectional imaging findings of two cases diagnosed as E-AML and pathological correlation of these aforementioned masses mimicking RCC.

Microwave treatment of renal cell carcinoma adjacent to renal sinus

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Gao, Yongyan; Liang, Ping; Yu, Xiaoling; Yu, Jie; Cheng, Zhigang; Han, Zhiyu; Duan, Shaobo; Huang, Hui

2016-01-01

Highlights: • This study shows US-guided microwave ablation appears to be a promising method to treat renal cell carcinoma adjacent to renal sinus. • The estimated 1-, 3- and 5-year RCC-related survival were 100%, 93.3% and 93.3%, respectively. • The estimated 1-, 3- and 5-year overall survival were 97.1%, 87.8%, 83.6%, respectively. • For patients with RCC ≤4 cm, initial ablation success was 100% (29/29) and the estimated 5-year disease-free survival were 81.5%. - Abstract: Purpose: To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for renal cell carcinoma (RCC) adjacent to renal sinus. Materials and methods: This retrospective study included 41 patients who underwent US-guided percutaneous MWA of 41 RCCs adjacent to the renal sinus from April 2006 to December 2015. Contrast-enhanced images of US and computed tomography (CT) or magnetic resonance (MR) imaging were performed at pre-ablation and 1 day, 1 month, 3 months, and every 6 months after ablation. Initial ablation success (IAS), disease-free survival (DFS), RCC-related survival (RRS), and overall survival (OS) were recorded at the follow-up visits. Results: IAS was achieved in 92.7% (38/41) of the study subjects. The IAS significantly differed between patients with RCCs ≤4 cm (100%, 29/29) and RCCs >4 cm (75%, 9/12, p = 0.021). During the median follow-up of 37.6 (range, 3.0–97.3) months, the estimated 1-, 3-, and 5-year DFS of patients with an initial tumor of ≤4 cm were 100%, 89.7%, and 81.5%, respectively. The 1-, 3-, and 5-year RRS were 100%, 93.3%, and 93.3%, respectively. The 1-, 3-, and 5-year OS were 97.1%, 87.8%, and 83.6%, respectively. The multivariate analysis using the Cox proportional hazard model revealed no independent predictor of recurrence among all the variables. There were no MWA-related deaths among the study subjects. One patient developed a retroperitoneal abscess after ablation. Conclusion: US-guided percutaneous MWA

Microwave treatment of renal cell carcinoma adjacent to renal sinus

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Gao, Yongyan, E-mail: gaoyongyan7@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Department of Ultrasound, The General Hospital of Chinese People’s Armed Police Forces, 69 Yongding Road, Beijing, 100039 (China); Liang, Ping, E-mail: liangping301@hotmail.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Yu, Xiaoling, E-mail: 784107477@qq.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Yu, Jie, E-mail: 1411495161@qq.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Cheng, Zhigang, E-mail: 13691367317@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Han, Zhiyu, E-mail: hanzhiyu122@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Duan, Shaobo, E-mail: Dustin2662@163.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China); Huang, Hui, E-mail: 309hh@sina.com [Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 (China)

2016-11-15

Highlights: • This study shows US-guided microwave ablation appears to be a promising method to treat renal cell carcinoma adjacent to renal sinus. • The estimated 1-, 3- and 5-year RCC-related survival were 100%, 93.3% and 93.3%, respectively. • The estimated 1-, 3- and 5-year overall survival were 97.1%, 87.8%, 83.6%, respectively. • For patients with RCC ≤4 cm, initial ablation success was 100% (29/29) and the estimated 5-year disease-free survival were 81.5%. - Abstract: Purpose: To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for renal cell carcinoma (RCC) adjacent to renal sinus. Materials and methods: This retrospective study included 41 patients who underwent US-guided percutaneous MWA of 41 RCCs adjacent to the renal sinus from April 2006 to December 2015. Contrast-enhanced images of US and computed tomography (CT) or magnetic resonance (MR) imaging were performed at pre-ablation and 1 day, 1 month, 3 months, and every 6 months after ablation. Initial ablation success (IAS), disease-free survival (DFS), RCC-related survival (RRS), and overall survival (OS) were recorded at the follow-up visits. Results: IAS was achieved in 92.7% (38/41) of the study subjects. The IAS significantly differed between patients with RCCs ≤4 cm (100%, 29/29) and RCCs >4 cm (75%, 9/12, p = 0.021). During the median follow-up of 37.6 (range, 3.0–97.3) months, the estimated 1-, 3-, and 5-year DFS of patients with an initial tumor of ≤4 cm were 100%, 89.7%, and 81.5%, respectively. The 1-, 3-, and 5-year RRS were 100%, 93.3%, and 93.3%, respectively. The 1-, 3-, and 5-year OS were 97.1%, 87.8%, and 83.6%, respectively. The multivariate analysis using the Cox proportional hazard model revealed no independent predictor of recurrence among all the variables. There were no MWA-related deaths among the study subjects. One patient developed a retroperitoneal abscess after ablation. Conclusion: US-guided percutaneous MWA

Effect of Sodium-Glucose Co-Transporter 2 Inhibitor, Dapagliflozin, on Renal Renin-Angiotensin System in an Animal Model of Type 2 Diabetes.

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Shin, Seok Joon; Chung, Sungjin; Kim, Soo Jung; Lee, Eun-Mi; Yoo, Young-Hye; Kim, Ji-Won; Ahn, Yu-Bae; Kim, Eun-Sook; Moon, Sung-Dae; Kim, Myung-Jun; Ko, Seung-Hyun

2016-01-01

Renal renin-angiotensin system (RAS) activation is one of the important pathogenic mechanisms in the development of diabetic nephropathy in type 2 diabetes. The aim of this study was to investigate the effects of a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, dapagliflozin, on renal RAS in an animal model with type 2 diabetes. Dapagliflozin (1.0 mg/kg, OL-DA) or voglibose (0.6 mg/kg, OL-VO, diabetic control) (n = 10 each) was administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats for 12 weeks. We used voglibose, an alpha-glucosidase inhibitor, as a comparable counterpart to SGLT2 inhibitor because of its postprandial glucose-lowering effect without proven renoprotective effects. Control Long-Evans Tokushima Otsuka (LT) and OLETF (OL-C) rats received saline (n = 10, each). Changes in blood glucose, urine albumin, creatinine clearance, and oxidative stress were measured. Inflammatory cell infiltration, mesangial widening, and interstitial fibrosis in the kidney were evaluated by histological analysis. The effects of dapagliflozin on renal expression of the RAS components were evaluated by quantitative RT-PCR in renal tissue. After treatment, hyperglycemia and urine microalbumin levels were attenuated in both OL-DA and OL-VO rather than in the OL-C group (P renal RAS component expression, oxidative stress and interstitial fibrosis in OLETF rats. We suggest that, in addition to control of hyperglycemia, partial suppression of renal RAS with an SGLT2 inhibitor would be a promising strategy for the prevention of treatment of diabetic nephropathy.

Renal angiographic and computed tomographic evaluation of local extension of renal cell carcinoma

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Masuda, Fujio; Onishi, Tetsuro; Sasaki, Tadamasa; Arai, Yoshikazu; Shoji, Ryo

1981-01-01

In 23 cases of renal cell carcinoma, the degree of local invasion of carcinoma was diagnosed using renal angiography and CT, and compared with the findings obtained by operation or autopsy. Among 5 cases in which the tumor was confined to the renal capsule, accurate diagnosis could be established with renal angiography in 4 cases and with CT in all of 5 cases. Both renal angiography and CT provided correct diagnosis in 7 of 8 cases in which the tumor showed infiltration extending to the perinephric fat. Out of 5 cases with tumor invasion of renal vein or inferior vena cava, diagnosis could be established correctly by renal angiography and CT in 3 cases. Among the remaining 2 cases the diagnosis could be established by renal angiography and CT in one each case. Among 5 cases with metastases to the regional lymph nodes, diagnosis could be established by renal angiography in only 2 cases, while all of 5 cases could be diagnosed by CT. In 3 cases where the tumor invaded an ajacent organ beyond Gerota's fastia, renal angiography could diagnose in none of the 3 cases while with CT all of 3 cases could successfully be diagnosed. The consistency of degree of local invasion as revealed by renal angiography and CT was seen in 15 of 23 cases (65%) for renal agniography and 20 of 23 cases (87%) for CT, indicating superiority of CT in this respect. In particular, CT appears to be more superior to renal angiography for determining whether the tumor confined to Gerota's fastia or it infiltrated over it. Both combined use of renal angiography and CT, the degree of infiltration of tumor could be diagnosed correctly in 22 of 23 cases (96%). (author)

Anticancer Drug 2-Methoxyestradiol Protects against Renal Ischemia/Reperfusion Injury by Reducing Inflammatory Cytokines Expression

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Ying-Yin Chen

2014-01-01

Full Text Available Background. Ischemia/reperfusion (I/R injury is a major cause of acute renal failure and allograft dysfunction in kidney transplantation. ROS/inflammatory cytokines are involved in I/R injury. 2-Methoxyestradiol (2ME2, an endogenous metabolite of estradiol, inhibits inflammatory cytokine expression and is an antiangiogenic and antitumor agent. We investigated the inhibitory effect of 2ME2 on renal I/R injury and possible molecular actions. Methods. BALB/c mice were intraperitoneally injected with 2ME2 (10 or 20 mg/kg or vehicle 12 h before and immediately after renal I/R experiments. The kidney weight, renal function, tubular damages, and apoptotic response were examined 24 h after I/R injury. The expression of mRNA of interleukin-1β, tumor necrosis factor- (TNF α, caspase-3, hypoxia inducible factor- (HIF 1α, and proapoptotic Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3 in kidney tissue was determined using RT-PCR, while the expression of nuclear factor κB (NF-κB, BCL-2, and BCL-xL, activated caspase-9, and HIF-1α was determined using immunoblotting. In vitro, we determined the effect of 2ME2 on reactive oxygen species (ROS production and cell viability in antimycin-A-treated renal mesangial (RMC and tubular (NRK52E cells. Results. Serum creatinine and blood urea nitrogen were significantly higher in mice with renal I/R injury than in sham control and in I/R+2ME2-treated mice. Survival in I/R+2ME2-treated mice was higher than in I/R mice. Histological examination showed that 2ME2 attenuated tubular damage in I/R mice, which was associated with lower expression TNF-α, IL-1β, caspase-9, HIF-1α, and BNIP3 mRNA in kidney tissue. Western blotting showed that 2ME2 treatment substantially decreased the expression of activated caspase-9, NF-κB, and HIF-1α but increased the antiapoptotic proteins BCL-2 and BCL-xL in kidney of I/R injury. In vitro, 2MR2 decreased ROS production and increased cell viability in antimycin

Oncogenic micro-RNAs and Renal Cell Carcinoma

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Cristina eGrange

2014-03-01

Full Text Available Tumor formation is a complex process that occurs in different steps and involves many cell types, including tumor cells, endothelial cells, and inflammatory cells, which interact to promote growth of the tumor mass and metastasization. Epigenetic alterations occurring in transformed cells result in de-regulation of miRNA expression (a class of small non-coding RNA that regulates multiple functions which contributes to tumorigenesis. The specific miRNAs, which have an aberrant expression in tumors, are defined as oncomiRNAs, and may be either over- or under-expressed, but down-regulation is most commonly observed.Renal cell carcinoma is a frequent form of urologic tumor, associated with an alteration of multiple signaling pathways. Many molecules involved in the progression of renal cell carcinomas, such as HIF, VEGF or mTOR, are possible targets of deregulated miRNAs. Within tumor mass, the cancer stem cell population is a fundamental component that promotes tumor growth. The cancer stem cell hypothesis postulates that cancer stem cells have the unique ability to self-renew and to maintain tumor growth and metastasis. Cancer stem cells present in renal cell carcinoma were shown to express the mesenchymal stem cell marker CD105 and to exhibit self-renewal and clonogenic properties, as well as the ability to generate serially transplantable tumors. The phenotype of cancer stem cell has been related to the potential to undergo the epithelial-mesenchymal transition, which has been linked to the expression pattern of tumorigenic miRNAs or down-regulation of anti-tumor miRNAs. In addition, the pattern of circulating miRNAs may allow discrimination between healthy and tumor patients. Therefore, a miRNA signature may be used as a tumor biomarker for cancer diagnosis, as well as to classify the risk of relapse and metastasis, and for a guide for therapy.

Genetic Targeting of Arginase-II in Mouse Prevents Renal Oxidative Stress and Inflammation in Diet-Induced Obesity.

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Huang, Ji; Rajapakse, Angana; Xiong, Yuyan; Montani, Jean-Pierre; Verrey, François; Ming, Xiu-Fen; Yang, Zhihong

2016-01-01

Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase-II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT) C57BL/6 mice and mice deficient in Arg-II gene (Arg-II -/- ) were fed with either a normal chow (NC) or a high-fat-diet (HFD) for 14 weeks (starting at the age of 7 weeks) to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal reactive oxygen species (ROS) levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II -/- mice. Moreover, mesangial expansion as analyzed by Periodic Acid Schiff (PAS) staining and renal expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg-II -/- mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II -/- mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development.

Genetic Targeting of Arginase-II in Mouse Prevents Renal Oxidative Stress and Inflammation in Diet-Induced Obesity

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Ji Huang

2016-11-01

Full Text Available Obesity is associated with development and progression of chronic kidney disease (CKD. Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I and arginase-II (Arg-II in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS, leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT C57BL/6 mice and mice deficient in Arg-II gene (Arg-II-/- were fed with either a normal chow (NC or a high-fat-diet (HFD for 14 weeks (starting at the age of 7 weeks to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal ROS levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II-/- mice. Moreover, mesangial expansion as analysed by Periodic Acid Schiff (PAS staining and renal expression of vascular adhesion molecule-1 (VCAM-1 and intercellular adhesion molecule-1 (ICAM-1 in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg-II-/- mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II-/- mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development.

Association of ABCB1 genetic variants with renal function in Africans and in Caucasians

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Elston Robert C

2008-06-01

Full Text Available Abstract Background The P-glycoprotein, encoded by the ABCB1 gene, is expressed in human endothelial and mesangial cells, which contribute to control renal plasma flow and glomerular filtration rate. We investigated the association of ABCB1 variants with renal function in African and Caucasian subjects. Methods In Africans (290 subjects from 62 pedigrees, we genotyped the 2677G>T and 3435 C>T ABCB1 polymorphisms. Glomerular filtration rate (GFR was measured using inulin clearance and effective renal plasma flow (ERPF using para-aminohippurate clearance. In Caucasians (5382 unrelated subjects, we analyzed 30 SNPs located within and around ABCB1, using data from the Affymetrix 500 K chip. GFR was estimated using the simplified Modification of the Diet in Renal Disease (MDRD and Cockcroft-Gault equations. Results In Africans, compared to the reference genotype (GG or CC, each copy of the 2677T and 3435T allele was associated, respectively, with: GFR higher by 10.6 ± 2.9 (P P = 0.06 mL/min; ERPF higher by 47.5 ± 11.6 (P P = 0.007 mL/min; and renal resistances lower by 0.016 ± 0.004 (P P = 0.004 mm Hg/mL/min. In Caucasians, we identified 3 polymorphisms in the ABCB1 gene that were strongly associated with all estimates of GFR (smallest P value = 0.0006, overall P = 0.014 after multiple testing correction. Conclusion Variants of the ABCB1 gene were associated with renal function in both Africans and Caucasians and may therefore confer susceptibility to nephropathy in humans. If confirmed in other studies, these results point toward a new candidate gene for nephropathy in humans.

Renal cell carcinoma presenting as mandibular metastasis

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Hassan Ahmadnia

2013-01-01

Full Text Available Renal clear cell carcinoma (RCC has different manifestations, including uncommon metastasis and paraneoplastic syndromes. Here we report a rare case of RCC presenting as metastasis to the mandible. A 57-year-old patient with mandibular swelling was referred to the dentist. After necessary evaluations, an incisional biopsy of mandible showed metastatic RCC. The patient was referred to the urologist. The patient underwent right radical nephrectomy. Pathological examination showed clear renal cell carcinoma. Every abnormal bone lesion in the oral cavity should be evaluated carefully and the possibility of a malignant lesion should always be considered.

Experimental depletion of different renal interstitial cell populations

International Nuclear Information System (INIS)

Bohman, S.O.; Sundelin, B.; Forsum, U.; Tribukait, B.

1988-01-01

To define different populations of renal interstitial cells and investigate some aspects of their function, we studied the kidneys of normal rats and rats with hereditary diabetes insipidus (DI, Brattleboro) after experimental manipulations expected to alter the number of interstitial cells. DI rats showed an almost complete loss of interstitial cells in their renal papillae after treatment with a high dose of vasopressin. In spite of the lack of interstitial cells, the animals concentrated their urine to the same extent as vasopressin-treated normal rats, indicating that the renomedullary interstitial cells do not have an important function in concentrating the urine. The interstitial cells returned nearly to normal within 1 week off vasopressin treatment, suggesting a rapid turnover rate of these cells. To further distinguish different populations of interstitial cells, we studied the distribution of class II MHC antigen expression in the kidneys of normal and bone-marrow depleted Wistar rats. Normal rats had abundant class II antigen-positive interstitial cells in the renal cortex and outer medulla, but not in the inner medulla (papilla). Six days after 1000 rad whole body irradiation, the stainable cells were almost completely lost, but electron microscopic morphometry showed a virtually unchanged volume density of interstitial cells in the cortex and outer medulla, as well as the inner medulla. Thus, irradiation abolished the expression of the class II antigen but caused no significant depletion of interstitial cells

Renal cell carcinoma and occupational exposure to chemicals in Canada

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Hu, J.; Mao, Y.; White, K. [Health Canada, Ottawa, ON (Canada). Population & Public Health Branch

2002-05-01

This study assesses the effect of occupational exposure to specific chemicals on the risk of renal cell carcinoma in people in Canada. Mailed questionnaires were used to obtain data on 1279 (691 male and 588 female) newly diagnosed, histologically confirmed renal cell carcinoma cases and 5370 population controls in eight Canadian provinces, between 1994 and 1997. Data were collected on socio-economic status, smoking habit, alcohol use, diet, residential and occupational histories, and years of exposure to any of 17 chemicals. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived using unconditional logistic regression. The study found an increased risk of renal cell carcinoma in males only, which was associated with occupational exposure to benzene; benzidine; coal tar, soot, pitch, creosote or asphalt; herbicides; mineral, cutting or lubricating oil; mustard gas; pesticides; and vinyl chloride. Very few females were exposed to specific chemicals in this study; further research is needed to clarify the association between occupational exposure to chemicals and renal cell carcinoma in females.

Arterial spin labelling MRI for detecting pseudocapsule defects and predicting renal capsule invasion in renal cell carcinoma.

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Zhang, H; Wu, Y; Xue, W; Zuo, P; Oesingmann, N; Gan, Q; Huang, Z; Wu, M; Hu, F; Kuang, M; Song, B

2017-11-01

To evaluate prospectively the performance of combining morphological and arterial spin labelling (ASL) magnetic resonance imaging (MRI) for detecting pseudocapsule defects in renal cell carcinoma (RCC), and to predict renal capsule invasion confirmed histopathologically. Twenty consecutive patients with suspicious renal tumours underwent MRI. Renal ASL imaging was performed and renal blood flow was measured quantitatively. The diagnostic performance of T2-weighted images alone, and a combination of T2-weighted and ASL images for predicting renal capsule invasion were assessed. Twenty renal lesions were evaluated in 20 patients. All lesions were clear cell RCCs (ccRCCs) confirmed at post-surgical histopathology. Fifteen ccRCCs showed pseudocapsule defects on T2-weighted images, of which 12 cases showed existing blood flow in defect areas on perfusion images. To predict renal capsule invasion, the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 71.4%, 86.7%, 100%, respectively, for T2-weighted images alone, and 92.3%, 100%, 100%, 87.5%, respectively, for the combination of T2-weighted and ASL images. ASL images can reflect the perfusion of pseudocapsule defects and as such, the combination of T2-weighted and ASL images produces promising diagnostic accuracy for predicting renal capsule invasion. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Renal Sinus Fat Invasion and Tumoral Thrombosis of the Inferior Vena Cava-Renal Vein: Only Confined to Renal Cell Carcinoma

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Turker Acar

2014-01-01

Full Text Available Epithelioid angiomyolipoma (E-AML, accounting for 8% of renal angiomyolipoma, is usually associated with tuberous sclerosis (TS and demonstrates aggressive behavior. E-AML is macroscopically seen as a large infiltrative necrotic tumor with occasional extension into renal vein and/or inferior vena cava. However, without history of TS, renal sinus and venous invasion E-AML would be a challenging diagnosis, which may lead radiologists to misinterpret it as a renal cell carcinoma (RCC. In this case presentation, we aimed to report cross-sectional imaging findings of two cases diagnosed as E-AML and pathological correlation of these aforementioned masses mimicking RCC.

Breast Metastasis from Renal Cell Carcinoma: A Case Report

International Nuclear Information System (INIS)

Kim, Seon Jeong; Kim, Ji Young; Jeong, Myeong Ja; Kim, Jae Hyung; Kim, Soung Hee; Kim, Soo Hyun; Jun, Woo Sun; Kim, Hyun Jung; Han, Se Hwan

2010-01-01

Metastatic breast cancer from renal cell carcinoma is extremely rare and has non-specific findings that include a well circumscribed lesion without calcification on mammography and a well circumscribed hypoechoic lesion without posterior acoustic shadowing on sonography. We report a case of metastatic breast cancer from renal cell carcinoma and describe the radiologic findings in a 63-year-old woman who has no history of primary neoplasm

Breast Metastasis from Renal Cell Carcinoma: A Case Report

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Kim, Seon Jeong; Kim, Ji Young; Jeong, Myeong Ja; Kim, Jae Hyung; Kim, Soung Hee; Kim, Soo Hyun; Jun, Woo Sun; Kim, Hyun Jung; Han, Se Hwan [Sanggye Paik Hospital, Seoul (Korea, Republic of)

2010-01-15

Metastatic breast cancer from renal cell carcinoma is extremely rare and has non-specific findings that include a well circumscribed lesion without calcification on mammography and a well circumscribed hypoechoic lesion without posterior acoustic shadowing on sonography. We report a case of metastatic breast cancer from renal cell carcinoma and describe the radiologic findings in a 63-year-old woman who has no history of primary neoplasm.

An unusual cause of acute renal failure in sickle cell disease

Science.gov (United States)

Rockx, Marie-Antoinette; Gibson, Ian W.; Reslerova, Martina

2009-01-01

A young female with sickle cell disease was treated for biopsy-proven IgA nephropathy. Serum creatinine levels resolved to normal range, but a year later, she presented with oedema, hypertension and acute renal failure. A repeat renal biopsy showed acute-on-chronic thrombotic microangiopathy (TMA). We suggest that circulating microparticles could be a pathophysiological link between sickle cell disease and the development of renal TMA. This case emphasizes the importance of a further biopsy for acutely declining renal function, even when a definite diagnosis has been made from a previous biopsy. PMID:25949348

Histones from Dying Renal Cells Aggravate Kidney Injury via TLR2 and TLR4

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Allam, Ramanjaneyulu; Scherbaum, Christina Rebecca; Darisipudi, Murthy Narayana; Mulay, Shrikant R.; Hägele, Holger; Lichtnekert, Julia; Hagemann, Jan Henrik; Rupanagudi, Khader Valli; Ryu, Mi; Schwarzenberger, Claudia; Hohenstein, Bernd; Hugo, Christian; Uhl, Bernd; Reichel, Christoph A.; Krombach, Fritz; Monestier, Marc; Liapis, Helen; Moreth, Kristin; Schaefer, Liliana

2012-01-01

In AKI, dying renal cells release intracellular molecules that stimulate immune cells to secrete proinflammatory cytokines, which trigger leukocyte recruitment and renal inflammation. Whether the release of histones, specifically, from dying cells contributes to the inflammation of AKI is unknown. In this study, we found that dying tubular epithelial cells released histones into the extracellular space, which directly interacted with Toll-like receptor (TLR)-2 (TLR2) and TLR4 to induce MyD88, NF-κB, and mitogen activated protein kinase signaling. Extracellular histones also had directly toxic effects on renal endothelial cells and tubular epithelial cells in vitro. In addition, direct injection of histones into the renal arteries of mice demonstrated that histones induce leukocyte recruitment, microvascular vascular leakage, renal inflammation, and structural features of AKI in a TLR2/TLR4-dependent manner. Antihistone IgG, which neutralizes the immunostimulatory effects of histones, suppressed intrarenal inflammation, neutrophil infiltration, and tubular cell necrosis and improved excretory renal function. In summary, the release of histones from dying cells aggravates AKI via both its direct toxicity to renal cells and its proinflammatory effects. Because the induction of proinflammatory cytokines in dendritic cells requires TLR2 and TLR4, these results support the concept that renal damage triggers an innate immune response, which contributes to the pathogenesis of AKI. PMID:22677551

A case report of renal cell carcinoma in a dog

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A.-S. Paşca

2013-10-01

Full Text Available Mix renal carcinoma was noticed during the necropsic examination of a 14 year old mix breed female. Tumours were bilateral and metastasis was noticed in the spleen and myocard. Histological examination evidenced morphological aspects characteristic to the mixt renal carcinoma. Histological aspects described in this individual characterize renal cell carcinoma, also known as renal adenocarcinoma, hypernephroma or, in older literature, Grawitz tumour.

Forty Years Abuse of Baking Soda, Rhabdomyolysis, Glomerulonephritis, Hypertension Leading to Renal Failure: A Case Report

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Terje Forslund M.D., Ph.D.

2008-01-01

Full Text Available We present a patient who had ingested sodium bicarbonate for treatment of alcoholic dyspepsia during forty years at increasing doses. During the last year he had used more than 50 grams daily. He presented with metabolic alkalosis, epileptic convulsions, subdural hematoma, hypertension and rhabdomyolysis with end stage renal failure, for which he had to be given regular intermittent hemodialysis treatment. Untreated hypertension and glomerulonephritis was probably present prior to all these acute incidents. Examination of the kidney biopsy revealed mesangial proliferative glomerulonephritis and arterial wall thickening causing nephrosclerosis together with interstitial calcinosis. The combination of all these pathologic changes might be responsible for the development of progressive chronic renal failure ending up with the need for continuous intermittent hemodialysis treatment.

Forty years abuse of baking soda, rhabdomyolysis, glomerulonephritis, hypertension leading to renal failure: a case report.

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Forslund, Terje; Koistinen, Arvo; Anttinen, Jorma; Wagner, Bodo; Miettinen, Marja

2008-01-01

We present a patient who had ingested sodium bicarbonate for treatment of alcoholic dyspepsia during forty years at increasing doses. During the last year he had used more than 50 grams daily. He presented with metabolic alkalosis, epileptic convulsions, subdural hematoma, hypertension and rhabdomyolysis with end stage renal failure, for which he had to be given regular intermittent hemodialysis treatment. Untreated hypertension and glomerulonephritis was probably present prior to all these acute incidents. Examination of the kidney biopsy revealed mesangial proliferative glomerulonephritis and arterial wall thickening causing nephrosclerosis together with interstitial calcinosis. The combination of all these pathologic changes might be responsible for the development of progressive chronic renal failure ending up with the need for continuous intermittent hemodialysis treatment.

Rice bran protein hydrolysates attenuate diabetic nephropathy in diabetic animal model.

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Boonloh, Kampeebhorn; Lee, Eun Soo; Kim, Hong Min; Kwon, Mi Hye; Kim, You Mi; Pannangpetch, Patchareewan; Kongyingyoes, Bunkerd; Kukongviriyapan, Upa; Thawornchinsombut, Supawan; Lee, Eun Young; Kukongviriyapan, Veerapol; Chung, Choon Hee

2018-03-01

Diabetic nephropathy (DN) is an important microvascular complication of uncontrolled diabetes. The features of DN include albuminuria, extracellular matrix alterations, and progressive renal insufficiency. Rice bran protein hydrolysates (RBPs) have been reported to have antihyperglycemic, lipid-lowering, and anti-inflammatory effects in diabetic rats. Our study was to investigate the renoprotective effects of RBP in diabetic animals and mesangial cultured cells. Eight-week-old male db/m and db/db mice were orally treated with tap water or RBP (100 or 500 mg/kg/day) for 8 weeks. At the end of the experiment, diabetic nephropathy in kidney tissues was investigated for histological, ultrastructural, and clinical chemistry changes, and biomarkers of angiogenesis, fibrosis, inflammation, and antioxidant in kidney were analyzed by Western blotting. Protection against proangiogenic proteins and induction of cytoprotection by RBP in cultured mesangial cells was evaluated. RBP treatment improved insulin sensitivity, decreased elevated fasting serum glucose levels, and improved serum lipid levels and urinary albumin/creatinine ratios in diabetic mice. RBP ameliorated the decreases in podocyte slit pore numbers, thickening of glomerular basement membranes, and mesangial matrix expansion and suppressed elevation of MCP-1, ICAM-1, HIF-1α, VEGF, TGF-β, p-Smad2/3, and type IV collagen expression. Moreover, RBP restored suppressed antioxidant Nrf2 and HO-1 expression. In cultured mesangial cells, RBP inhibited high glucose-induced angiogenic protein expression and induced the expression of Nrf2 and HO-1. RBP attenuates the progression of diabetic nephropathy and restored renal function by suppressing the expression of proangiogenic and profibrotic proteins, inhibiting proinflammatory mediators, and restoring the antioxidant and cytoprotective system.

PRIMARY SQUAMOUS CELL CARCINOMA OF RENAL PELVIS ASSOCIATED WITH RENAL CALCULUS AND RECURRENT PYONEPHROSIS

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Hoti Lal

2015-11-01

Full Text Available Primary Squamous Cell Carcinoma in the kidney is a rare malignant neoplasm associated with nephrolithiasis, typically monobacterial pyonephrosis and rarely Xanthogranulomatous pyelonephritis. It is an aggressive disease with a poor prognosis mostly due to lack of presenting clinical features like a palpable mass, gross haematuria and pain. We report a case presenting with renal calculus and pyonephrosis managed initially with percutaneous nephrostomy followed by nephrectomy due to complete loss of renal function. Histopathological evaluation revealed poorly differentiated squamous cell carcinoma which is managed by chemotherapy, although initially beneficial, patients later develop disseminated metastatic disease which holds a poor prognosis.

Molecular features of renal cell carcinoma: early diagnostics and perspectives for therapy

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O. V. Kovaleva

2014-01-01

Full Text Available Kidney cancer (renal cell carcinoma is one of the major problems of modern urological oncology. In Russia renal cell carcinoma accountsfor 4.3 % of all cancers. The global incidence of renal cell carcinoma has increased over the past two decades. Worldwide renal cell carcinoma accounts for 3.6 % of all cancers and is 10th frequent malignancy. For some malignancies, for instance tumours of prostate, there are markers known that allowed improved early diagnostics. Kidney cancer, however, remains to be hard to diagnose and to treat, since the symptoms can be detected on advanced stages of the disease. In Russia 75.4 % of renal cell carcinoma cases detected at the stage of local and locally advanced disease. Though there are various target drugs on the market aimed to treat this disease, the results of renal cell carcinoma treatment did not reach any substantial success. Most of existing target drugs for kidney cancer treatment include inhibitors of a single signalingpathway regulated by VHL1, which expression is lost in the vast majority of renal-cell carcinomas. Till now existing drugs did not reach sufficient efficacy. Therefore, it is highly important to search for new signaling pathways, regulating such cellular processes as proliferation, migration and apoptosis. Further, prognostic markers and therapy targets identified so far are not sufficient and poorly specific. Therefore identification and validation of new markers, and especially new specific targets for the treatment of kindey oncopathologies is highly important and timely task.

A brief symptom index for advanced renal cell carcinoma

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Cella David

2006-09-01

Full Text Available Abstract Background Our objective was to test a brief, symptom index for advanced renal cell carcinoma, a disease affecting over 38,000 Americans each year and often diagnosed in late stages. Methods We conducted secondary data analyses on patient-reported outcomes of 209 metastatic renal cell carcinoma patients participating in a Phase III clinical trial. Patient-reported outcomes, obtained from the FACT-Biological Response Modifier (FACT-BRM scale, were available at baseline, 2, and 8 weeks. We analyzed data from eight FACT-BRM items previously identified by clinical experts to represent the most important symptoms of advanced renal cell carcinoma. Items comprising this index assess nausea, pain, appetite, perceived sickness, fatigue and weakness, with higher scores indicating fewer symptoms. We determined reliability and validity of the index and estimated a minimally important difference. Results The index had excellent internal reliability at all three time points (alphas ≥ 0.83. Baseline scores were able to discriminate patients across Karnofsky performance status, number of metastatic sites, and risk group categories (ps Conclusion The 8-item index of patient-reported symptoms of renal cell carcinoma appears to be a psychometrically sound measure. It is a brief, reliable, and valid measure that can easily be adapted for use in clinical trials and observational studies.

Characterizing the outcomes of metastatic papillary renal cell carcinoma

DEFF Research Database (Denmark)

Connor Wells, John; Donskov, Frede; Fraccon, Anna P

2017-01-01

Outcomes of metastatic papillary renal cell carcinoma (pRCC) patients are poorly characterized in the era of targeted therapy. A total of 5474 patients with metastatic renal cell carcinoma (mRCC) in the International mRCC Database Consortium (IMDC) were retrospectively analyzed. Outcomes were...... compared between clear cell (ccRCC; n = 5008) and papillary patients (n = 466), and recorded type I and type II papillary patients (n = 30 and n = 165, respectively). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) favored ccRCC over pRCC. OS was 8 months longer...

Papillary renal cell carcinoma in allograft kidney

International Nuclear Information System (INIS)

Roy, Catherine; El Ghali, Sofiane; Buy, Xavier; Gangi, Afshin; Lindner, Veronique

2005-01-01

Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. Its occurrence in allograft transplanted kidney has not been debated in the literature. We report two pathologically proven cases and discuss the clinical hypothesis for such neoplasms and the aspect on MR images. The paramagnetic effect of the iron associated with an absence of signal coming from calcifications is a plausible explanation for this unusual hypointense appearance on T2-weighted sequence. (orig.)

Laparoscopic bilateral nephroureterectomy and bladder cuff excision for native renal pelvic and ureteral transitional cell carcinoma after renal transplantation.

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Chen C

2003-01-01

Full Text Available A 37-years-old female who was suffering from end-stage renal disease for about 6 years received allograft renal transplantation 4 years ago. She has been receiving 50mg of Cyclosporin A orally daily for immuno-suppression since then. Gross haematuria was noted and computerised tomography showed native left renal pelvic and ureteral multi-focal transitional cell carcinoma with severe hydronephrosis. Laparoscopic bilateral nephroureterectomy and bladder cuff excision were performed. In the past, history of previous operation was considered a relative contraindication for laparoscopic surgery. To our knowledge, we present the first case of laparoscopic treatment for native renal pelvic and ureteral transitional cell carcinoma after renal allograft transplantation without a hand-assisted device. This case shows the feasibility of laparoscopic bilateral nephroureterectomy in patients with transplanted kidneys.

Triphasic and epithelioid minimal fat renal angiomyolipoma and clear cell renal cell carcinoma: qualitative and quantitative CEUS characteristics and distinguishing features.

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Lu, Qing; Li, Cui-xian; Huang, Bei-jian; Xue, Li-yun; Wang, Wen-ping

2015-02-01

To determine the contrast-enhanced ultrasonography (CEUS) characteristics of minimal fat renal angiomyolipoma (AML) (triphasic and epithelioid) and compare them to each other and to clear cell renal cell carcinoma (ccRCC) to explore their differential diagnostic clue. Qualitative and quantitative CEUS analyses were retrospectively conducted for epithelioid renal AMLs (EAMLs) (n = 15), triphasic minimal fat AMLs (TAMLs) (n = 25), and ccRCCs (n = 113). Enhancement patterns and features with CEUS were qualitatively evaluated. As for the quantitative parameters, rise times (RT), time to peak (TTP), and tumor-to-cortex enhancement ratio (TOC ratio) were compared among these renal tumor histotypes. No significant differences were detected on conventional ultrasound in the three histotypes of renal tumor. On qualitative CEUS analysis, centripetal enhancement in cortical phase (73.3% in EAMLs, 84.0% in TAMLs vs. 18.6% in ccRCCs, p qualitative and quantitative characteristics made no significant difference between EAMLs and TAMLs. In the differential diagnosis of EAMLs from TAMLs, pseudocapsule sign was valuable (40.0% in EAMLs vs. 0.0% in TAMLs, p 97.34% as the criteria to differentiate ccRCCs and EAMLs from TAMLs, the sensitivity and specificity were 80.0% and 87.5%, respectively. Qualitative and quantitative CEUS analyses are helpful in the differential diagnosis of ccRCCs, EAMLs, and TAMLs.

Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

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Kelly, K J; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Gattone, Vincent H; Dominguez, Jesus H

2015-01-01

Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

Insulin-like growth factor-1 sustains stem cell mediated renal repair.

NARCIS (Netherlands)

Imberti, B.; Morigi, M.; Tomasoni, S.; Rota, C.; Corna, D.; Longaretti, L.; Rottoli, D.; Valsecchi, F.; Benigni, A.; Wang, J.; Abbate, M.; Zoja, C.; Remuzzi, G.

2007-01-01

In mice with cisplatin-induced acute kidney injury, administration of bone marrow-derived mesenchymal stem cells (MSC) restores renal tubular structure and improves renal function, but the underlying mechanism is unclear. Here, we examined the process of kidney cell repair in co-culture experiments

The effect of hypoxia and reoxygenation in the response of mesangial cells to angiotensin II in vitro

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Clara Versolato Razvickas

2013-12-01

Full Text Available INTRODUCTION: Mesangial cells (MC may be involved in the glomerular alterations induced by ischemia/reperfusion injury. OBJECTIVE: To evaluate the response of immortalized MC (IMC to 30 minutes of hypoxia followed by reoxygenation periods of 30 minutes (H/R30 or 24 hours (H/R24. METHODS: The intracellular calcium concentration ([Ca+2]i was measured before (baseline and after adding angiotensin II (AII, 10-5 M in the presence and absence of glybenclamide (K ATP channel blocker. We estimated the level of intracellular ATP, nitric oxide (NO and PGE2. RESULTS: ATP concentration decreased after hypoxia and increased after reoxygenation. Hypoxia and H/R induced increases in basal [Ca+2]i. AII induced increases in [Ca+2]i in normoxia (97 ± 9%, hypoxia (72 ± 10% or HR30 (85 ± 17% groups, but there was a decrease in the response to AII in group H/R24 since the elevation in [Ca+2]i was significantly lower than in control (61 ± 10%, p < 0.05. Glybenclamide did not modify this response. It was observed a significant increase in NO generation after 24 hours of reoxygenation, but no difference in PGE2 production was observed. Data suggest that H/R injury is characterized by increased basal [Ca+2]i and by an impairment in the response of cells to AII. Results suggest that the relative insensibility to AII may be at least in part mediated by NO but not by prostaglandins or vasodilator K ATP channels. CONCLUSION: H/R caused dysfunction in IMC characterized by increases in basal [Ca+2]i during hypoxia and reduction in the functional response to AII during reoxygenation.

Pattern multiplicity and fumarate hydratase (FH)/S-(2-succino)-cysteine (2SC) staining but not eosinophilic nucleoli with perinucleolar halos differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas from kidney tumors without FH gene alteration.

Science.gov (United States)

Muller, Marie; Guillaud-Bataille, Marine; Salleron, Julia; Genestie, Catherine; Deveaux, Sophie; Slama, Abdelhamid; de Paillerets, Brigitte Bressac; Richard, Stéphane; Benusiglio, Patrick R; Ferlicot, Sophie

2018-02-06

Hereditary leiomyomatosis and renal cell carcinoma syndrome is characterized by an increased risk of agressive renal cell carcinoma, often of type 2 papillary histology, and is caused by FH germline mutations. A prominent eosinophilic macronucleolus with a perinucleolar clear halo is distinctive of hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma according to the 2012 ISUP and 2016 WHO kidney tumor classification. From an immunohistochemistry perspective, tumors are often FH-negative and S-(2-succino)-cysteine (2SC) positive. We performed a pathology review of 24 renal tumors in 23 FH mutation carriers, and compared them to 12 type 2 papillary renal cell carcinomas from FH wild-type patients. Prominent eosinophilic nucleoli with perinucleolar halos were present in almost all FH-deficient renal cell carcinomas (23/24). Unexpectedly, they were also present in 58% of type 2 papillary renal cell carcinomas from wild-type patients. Renal cell carcinoma in mutation carriers displayed a complex architecture with multiple patterns, typically papillary, tubulopapillary, and tubulocystic, but also sarcomatoid and rhabdoid. Such pattern diversity was not seen in non-carriers. FH/2SC immunohistochemistry was informative as all hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas were either FH- or 2SC+. For FH and 2SC immunohistochemistries taken separately, sensitivity of negative anti-FH immunohistochemistry was 87.5% and specificity was 100%. For positive anti-2SC immunohistochemistry, sensitivity, and specificity were 91.7% and 91.7%, respectively. All FH wild-type renal cell carcinoma were FH-positive, and all but one were 2SC-negative. In conclusion, multiplicity of architectural patterns, rhabdoid/sarcomatoid components and combined FH/2SC staining, but not prominent eosinophilic nucleoli with perinucleolar halos, differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal

Multilocular cystic renal cell carcinoma: imaging and clinical correlation

International Nuclear Information System (INIS)

Xu Yong; Zhang Sheng

2013-01-01

Multilocular cystic renal cell carcinoma (MCRCC) is a subtype of clear cell renal cell carcinoma and has mild clinical symptoms and a favorable prognosis. Accordingly, nephron-sparing surgery is recommended as a therapeutic strategy. If histologic subtype of MCRCC can be predicted preoperatively with an acceptable level of accuracy, it may be important in predicting prognosis and make clinical management. Most MCRCCs show characteristic cross-sectional imaging findings and permit accurate diagnosis before the treatment. Cross -sectional imaging of MCRCC reveals a well -defined multilocular cystic mass with irregularly enhanced thickened septa and without enhanced intracystic solid nodule. It is often classified as Bosniak classification Ⅲ , which is significantly different from that of other renal cystic masses. The clinical, pathologic, and radiologic features of MCRCC were discussed and illustrated in this article. The role of the imaging preoperative evaluation for MCRCC, and management implications were emphasized. (authors)

Renal amyloidosis in a child with sickle cell anemia.

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Simşek, Behçet; Bayazit, Aysun K; Ergin, Melek; Soran, Mustafa; Dursun, Hasan; Kilinc, Yurdanur

2006-06-01

The kidney is frequently affected in patients with sickle cell syndrome, i.e., homozygous and heterozygous patients, with a consequently large spectrum of renal abnormalities that may range from minimal functional changes to chronic renal failure. Here, we present a 13-year-old boy with sickle cell anemia (SCA) (HbSS) who was referred to our unit with nephrotic syndrome. Renal biopsy revealed AA type amyloidosis on the basis of light microscopic findings, indicating Congo red staining and immunohistochemistry. He had neither a family history of familial Mediterranean fever (FMF) nor any complaint of recurrent abdominal pain, arthritis, and fever, but frequent painful vaso-occlusive crises. The patient was found to have no MEFV gene (Mediterranean feVer) mutations either. Painful episodic attacks might provoke recurrent acute inflammation, leading to repeated stimulation of acute phase responses and cause secondary amyloidosis. To our knowledge, this boy is the first case of SCA complicated by renal amyloidosis observed in childhood.

Implications of Von Hippel-Lindau Syndrome and Renal Cell Carcinoma

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Kenan Ashouri

2015-09-01

Full Text Available Von Hippel-Lindau syndrome (VHLS is a rare hereditary neoplastic disorder caused by mutations in the vhl gene leading to the development of tumors in several organs including the central nervous system, pancreas, kidneys, and reproductive organs. Manifestations of VHLS can present at different ages based on the affected organ and subclass of disease. In the subclasses of VHLS that cause renal disease, renal involvement typically begins closer to the end of the second decade of life and can present in different ways ranging from simple cystic lesions to solid tumors. Mutations in vhl are most often associated with clear cell renal carcinoma, the most common type of renal cancer, and also play a major role in sporadic cases of clear cell renal carcinoma. The recurrent, multifocal nature of this disease presents difficult challenges in the long-term management of patients with VHLS. Optimization of renal function warrants the use of several different approaches common to the management of renal carcinoma such as nephron sparing surgery, enucleation, ablation, and targeted therapies. In VHLS, renal lesions of 3 cm or bigger are considered to have metastatic potential and even small lesions often harbor malignancy. Many of the aspects of management revolve around optimizing both oncologic outcome and long-term renal function. As new surgical strategies and targeted therapies develop, the management of this complex disease evolves.  This review will discuss the key aspects of the current management of VHLS.

Cell renewal of glomerular cell types in normal rats. An autoradiographic analysis

International Nuclear Information System (INIS)

Pabst, R.; Sterzel, R.B.

1983-01-01

Normal adult Sprague-Dawley rats received either a single or repetitive injection of the DNA precursor 3 H-thymidine ( 3 H-TdR). For autoradiography semi-thin sections were prepared 2 hr to 14 days after labeling. The majority of labeled cells noted in glomerular tufts were endothelial cells. Mesangial cells had a lower production rate. Podocytes revealed no evidence of proliferation. Bowman's capsule cells showed a higher labeling index than tuft cells at all times. Neither the urinary nor the vascular pole was found to be a proliferative zone for Bowman's capsule cells. The flash and repetitive labeling experiments demonstrated a constant rate of cell renewal of about 1% per day, resulting in a long life span for endothelial and mesangial cells as well as Bowman's capsule cells. These data provide a basis for cell kinetic studies in models of glomerular diseases

Overexpressed CacyBP/SIP leads to the suppression of growth in renal cell carcinoma

International Nuclear Information System (INIS)

Sun, Shiren; Ning, Xiaoxuan; Liu, Jie; Liu, Lili; Chen, Yu; Han, Shuang; Zhang, Yanqi; Liang, Jie; Wu, Kaichun; Fan, Daiming

2007-01-01

Calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP), a target protein of S100, has been identified as a component of a novel ubiquitinylation complex leading to β-catenin degradation, which was found to be related to the malignant phenotypes of gastric cancer. However, the roles of CacyBP/SIP in renal cell carcinoma still remain unclear. In the present study, we had analyzed the expression of the CacyBP/SIP protein in human renal cancer cells and clinical tissue samples. The possible roles of CacyBP/SIP in regulating the malignant phenotype of renal cancer cells were also investigated. The results demonstrated that the expression of CacyBP/SIP was markedly down-regulated in renal cell carcinoma tissues and cell lines. Ectopic overexpression of CacyBP/SIP in A498 cells inhibited the proliferation of this cell and delayed cell cycle progression significantly, which might be related to the down-regulation of Cyclin D1 through reducing β-catenin protein. CacyBP/SIP also suppressed colony formation in soft agar and its tumorigenicity in nude mice. Taken together, our work showed that CacyBP/SIP, as a novel down-regulated gene in renal cell carcinoma, suppressed proliferation and tumorigenesis of renal cancer cells

[Renal cell carcinoma producing erythrocytosis due to inappropriate production of erythropoietin].

Science.gov (United States)

Villanueva-Gimeno, M M; Vicario-Bermúdez, J M; Fonseca-López, Ch; Caballero-Castro, J P; Zabala-López, S I; Sánchez-Elipe, M A; González-Gómez, N

2013-01-01

Erythrocytosis, or polycythaemia, is an increase, in absolute terms, of the erythrocyte mass. The most common solid tumour related to this phenomenon is renal cell carcinoma, which can produce erythrocytosis by increasing erythropoietin production. About 30% of symptomatic renal cell carcinomas are diagnosed due to the appearance of a paraneoplastic syndrome. Polycythaemia is one of these. Surgery, (radical or partial nephrectomy), is the treatment of choice in renal cell carcinoma and helps to keep the erythrocytosis situation under control. Copyright © 2011 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Polyploidy and Mitotic Cell Death Are Two Distinct HIV-1 Vpr-Driven Outcomes in Renal Tubule Epithelial Cells.

Science.gov (United States)

Payne, Emily H; Ramalingam, Dhivya; Fox, Donald T; Klotman, Mary E

2018-01-15

Prior studies have found that HIV, through the Vpr protein, promotes genome reduplication (polyploidy) in infection-surviving epithelial cells within renal tissue. However, the temporal progression and molecular regulation through which Vpr promotes polyploidy have remained unclear. Here we define a sequential progression to Vpr-mediated polyploidy in human renal tubule epithelial cells (RTECs). We found that as in many cell types, Vpr first initiates G 2 cell cycle arrest in RTECs. We then identified a previously unreported cascade of Vpr-dependent events that lead to renal cell survival and polyploidy. Specifically, we found that a fraction of G 2 -arrested RTECs reenter the cell cycle. Following this cell cycle reentry, two distinct outcomes occur. Cells that enter complete mitosis undergo mitotic cell death due to extra centrosomes and aberrant division. Conversely, cells that abort mitosis undergo endoreplication to become polyploid. We further show that multiple small-molecule inhibitors of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, including those that target ATR, ATM, and mTOR, indirectly prevent Vpr-mediated polyploidy by preventing G 2 arrest. In contrast, an inhibitor that targets DNA-dependent protein kinase (DNA-PK) specifically blocks the Vpr-mediated transition from G 2 arrest to polyploidy. These findings outline a temporal, molecularly regulated path to polyploidy in HIV-positive renal cells. IMPORTANCE Current cure-focused efforts in HIV research aim to elucidate the mechanisms of long-term persistence of HIV in compartments. The kidney is recognized as one such compartment, since viral DNA and mRNA persist in the renal tissues of HIV-positive patients. Further, renal disease is a long-term comorbidity in the setting of HIV. Thus, understanding the regulation and impact of HIV infection on renal cell biology will provide important insights into this unique HIV compartment. Our work identifies mechanisms that distinguish

Chronological alterations of diagnostic imaging of renal cell carcinoma

International Nuclear Information System (INIS)

Arima, Kiminobu; Sugimura, Yoshiki; Yanagawa, Makoto; Tochigi, Hiromi; Kawamura, Juichi

1994-01-01

A review of 156 cases of renal cell carcinoma diagnosed during a 20-year period demonstrated the changes of initial signs/symptoms and imaging modalities for detection and definition. According to the imaging modality used for diagnosing renal cell carcinoma, clinical pictures were chronologically examined over 4 periods: 1973 to 1979 (before CT era), 1980 to 1984 (early CT era), 1985 to 1987 (CT era) and 1988 to 1992 (CT/MRI era). With regards to initial signs or symptoms, the proportion of classical trials has gradually decreased, while that of tumors noted incidentally has increased. As for imaging modalities for detection, the proportion of IVP has gradually decreased and that of CT and US has increased over the periods. With regard to imaging modalities for definition, the proportion of angiography has decreased and that of CT has increased. From chronological changes in clinical pictures and imaging modalities, we suggested a decision tree of imaging modalities for detection and definition of renal cell carcinoma. (author)

Clinical and pathological features of papillary renal cell carcinoma ...

African Journals Online (AJOL)

Introduction and objectives: Papillary renal cell carcinoma (PRCC) accounts for 10–15% of renal tumors in adults. This type of tumor contains more than 75% of tubulo-papillary structures and is divided histologically into two subtypes. The distinction between these two subtypes is essential because of their prognostic value.

Síndrome de Denys-Drash: Presentación de un caso DENYS-DRASH'S SYNDROME: A CASE REPORT

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Neri Georgina Campañá Cobas

2005-03-01

Full Text Available El síndrome de Denys-Drash se caracteriza por pseudohemafroditismo masculino, tumor de Wilms y glomerulopatía con rápida progresión a la insuficiencia renal terminal, es producido por una mutación en el gen supresor TW1 localizado en el cromosoma 11p 13. La lesión glomerular se caracteriza por una esclerosis mesangial difusa. Reportamos un caso con genitales ambiguos, cariotipo 46 XY, síndrome nefrótico congénito a los 7 días de nacido, con rápida progresión a la insuficiencia renal terminal. Se hizo necesaria la diálisis peritoneal, y murió al mes de edad por sepsis generalizada. En el análisis del tejido renal se demuestra la esclerosis mesangial difusa.Denys-Drash's syndrome is characterized by male pseudohermaphroditism, Wilms' tumor and glomerulopathy with fast progression to terminal renal failure. It is produced by a mutation in the TW1 suppressor gene located in the chromosome 11p 13. The glomerular lesion is characterized by a diffuse mesangial sclerosis. A case with ambiguous genitalia, 46 XY karyotype, and congenital nephrotic syndrome at 7 days of age, with fast progression to terminal renal failure, is reported. Peritoneal dialysis was necessary and the patient died at one month of age due to generalized sepsis. The diffuse mesangial sclerosis is showed in the analysis of the renal tissue.

Renal cell apoptosis in human lupus nephritis: a histological study

DEFF Research Database (Denmark)

Faurschou, M; Penkowa, Milena; Andersen, C B

2009-01-01

Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney...... biopsies from 35 patients with lupus nephritis by means of terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling (TUNEL). Five samples of normal kidney tissue served as control specimens. We did not observe apoptotic glomerular cells in any...... cells constitute a quantitatively important source of auto-antibody-inducing nuclear auto-antigens in human lupus nephritis....

Cells derived from young bone marrow alleviate renal aging.

Science.gov (United States)

Yang, Hai-Chun; Rossini, Michele; Ma, Li-Jun; Zuo, Yiqin; Ma, Ji; Fogo, Agnes B

2011-11-01

Bone marrow-derived stem cells may modulate renal injury, but the effects may depend on the age of the stem cells. Here we investigated whether bone marrow from young mice attenuates renal aging in old mice. We radiated female 12-mo-old 129SvJ mice and reconstituted them with bone marrow cells (BMC) from either 8-wk-old (young-to-old) or 12-mo-old (old-to-old) male mice. Transfer of young BMC resulted in markedly decreased deposition of collagen IV in the mesangium and less β-galactosidase staining, an indicator of cell senescence. These changes paralleled reduced expression of plasminogen activator inhibitor-1 (PAI-1), PDGF-B (PDGF-B), the transdifferentiation marker fibroblast-specific protein-1 (FSP-1), and senescence-associated p16 and p21. Tubulointerstitial and glomerular cells derived from the transplanted BMC did not show β-galactosidase activity, but after 6 mo, there were more FSP-1-expressing bone marrow-derived cells in old-to-old mice compared with young-to-old mice. Young-to-old mice also exhibited higher expression of the anti-aging gene Klotho and less phosphorylation of IGF-1 receptor β. Taken together, these data suggest that young bone marrow-derived cells can alleviate renal aging in old mice. Direct parenchymal reconstitution by stem cells, paracrine effects from adjacent cells, and circulating anti-aging molecules may mediate the aging of the kidney.

An aggressive merkel cell carcinoma in a patient with chronic renal failure

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Sevda Gizlenti

2014-12-01

Full Text Available Merkel cell carcinoma (MCC is a rare cutaneous tumor arising from neuroendocrine cells and Merkel cells. Early diagnosis and treatment is important because of its aggressive course. We here report a 61 years old man with chronic renal failure, 3x5 cm mass on his right leg and inguinal-paraaortic lymph node metastases and resulting in death. MCC in the literature of the AIDS disease, organ transplantation, immunosuppressive therapy areas, and additional malignancies (multiple myeloma, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and melanoma have been reported in patients with increased incidence. Up to date a patient with renal transplantation and Merkel cell carcinoma have been reported in the literature, Merkel cell carcinoma with chronic renal failure have not been reported.

MiT family translocation renal cell carcinoma.

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Argani, Pedram

2015-03-01

The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MiTF. Gene fusions involving two of these transcription factors have been identified in renal cell carcinoma (RCC). The Xp11 translocation RCCs were first officially recognized in the 2004 WHO renal tumor classification, and harbor gene fusions involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. These two subtypes of translocation RCC have many similarities. Both were initially described in and disproportionately involve young patients, though adult translocation RCC may overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the Xp11 translocation RCCs frequently have clear cells with papillary architecture and abundant psammomatous bodies, while the t(6;11) RCCs frequently have a biphasic appearance with both large and small epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other. Both of these RCCs underexpress epithelial immunohistochemical markers like cytokeratin and epithelial membrane antigen (EMA) relative to most other RCCs. Unlike other RCCs, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, on the basis of clinical, morphologic, immunohistochemical, and genetic similarities, the 2013 ISUP Vancouver classification of renal neoplasia grouped these two neoplasms together under the heading of "MiT family translocation RCC." This review summarizes our current knowledge of these recently described RCCs. Copyright © 2015 Elsevier Inc. All rights reserved.

Renal cells activate the platelet receptor CLEC-2 through podoplanin

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Christou, Charita M.; Pearce, Andrew C.; Watson, Aleksandra A.; Mistry, Anita R.; Pollitt, Alice Y.; Fenton-May, Angharad E.; Johnson, Louise A.; Jackson, David G.; Watson, Steve P.; O'Callaghan, Chris A.

2009-01-01

We have recently shown that the C-type lectin-like receptor, CLEC-2, is expressed on platelets and that it mediates powerful platelet aggregation by the snake venom toxin, rhodocytin. In addition, we have provided indirect evidence for an endogenous ligand for CLEC-2 in renal cells expressing human immunodeficiency virus type 1 (HIV-1). This putative ligand facilitates transmission of HIV through its incorporation into the viral envelope and binding to CLEC-2 on platelets. The aim of this study was to identify the ligand on these cells which binds to CLEC-2 on platelets. Recombinant CLEC-2 exhibits specific binding to 293T cells in which the HIV can be grown. Further, 293T cells activate both platelets and CLEC-2-transfected DT-40 B cells. The transmembrane protein podoplanin was identified on 293T cells and demonstrated to mediate both binding of 293T cells to CLEC-2 and 293T cell activation of CLEC-2-transfected DT-40 B cells. Podoplanin is expressed on renal cells (podocytes). Further, a direct interaction between CLEC-2 and podoplanin was confirmed using surface plasmon resonance and was shown to be independent of glycosylation of CLEC-2. The interaction has an affinity of 24.5 ± 3.7μM. The present study identifies podoplanin as a ligand for CLEC-2 on renal cells. PMID:18215137

Increased circulating follicular helper T cells with decreased programmed death-1 in chronic renal allograft rejection.

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Shi, Jian; Luo, Fengbao; Shi, Qianqian; Xu, Xianlin; He, Xiaozhou; Xia, Ying

2015-11-03

Chronic antibody-mediated rejection is a major issue that affects long-term renal allograft survival. Since follicular helper T (Tfh) cells promote the development of antigen-specific B cells in alloimmune responses, we investigated the potential roles of Tfh cells, B cells and their alloimmune-regulating molecules in the pathogenesis of chronic renal allograft rejection in this study. The frequency of Tfh, B cells and the levels of their alloimmune-regulating molecules including chemokine receptor type 5 (CXCR5), inducible T cell co-stimulator (ICOS), programmed death-1 (PD-1), ICOSL, PDL-1 and interleukin-21 (IL-21), of peripheral blood were comparatively measured in 42 primary renal allograft recipients within 1-3 years after transplantation. Among them, 24 patients had definite chronic rejection, while other 18 patients had normal renal function. Tfh-cell ratio was significantly increased with PD-1 down-regulation in the patients with chronic renal allograft rejection, while B cells and the alloimmune-regulating molecules studied did not show any appreciable change in parallel. The patients with chronic renal allograft rejection have a characteristic increase in circulating Tfh cells with a decrease in PD-1 expression. These pathological changes may be a therapeutic target for the treatment of chronic renal allograft rejection and can be useful as a clinical index for monitoring conditions of renal transplant.

Regulatory T-Cell Augmentation or Interleukin-17 Inhibition Prevents Calcineurin Inhibitor-Induced Hypertension in Mice.

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Chiasson, Valorie L; Pakanati, Abhinandan R; Hernandez, Marcos; Young, Kristina J; Bounds, Kelsey R; Mitchell, Brett M

2017-07-01

The immunosuppressive calcineurin inhibitors cyclosporine A and tacrolimus alter T-cell subsets and can cause hypertension, vascular dysfunction, and renal toxicity. We and others have reported that cyclosporine A and tacrolimus decrease anti-inflammatory regulatory T cells and increase proinflammatory interleukin-17-producing T cells; therefore, we hypothesized that inhibition of these effects using noncellular therapies would prevent the hypertension, endothelial dysfunction, and renal glomerular injury induced by calcineurin inhibitor therapy. Daily treatment of mice with cyclosporine A or tacrolimus for 1 week significantly decreased CD4 + /FoxP3 + regulatory T cells in the spleen and lymph nodes, as well as induced hypertension, vascular injury and dysfunction, and glomerular mesangial expansion in mice. Daily cotreatment with all-trans retinoic acid reported to increase regulatory T cells and decrease interleukin-17-producing T cells, prevented all of the detrimental effects of cyclosporine A and tacrolimus. All-trans retinoic acid also increased regulatory T cells and prevented the hypertension, endothelial dysfunction, and glomerular injury in genetically modified mice that phenocopy calcineurin inhibitor-treated mice (FKBP12-Tie2 knockout). Treatment with an interleukin-17-neutralizing antibody also increased regulatory T-cell levels and prevented the hypertension, endothelial dysfunction, and glomerular injury in cyclosporine A-treated and tacrolimus-treated mice and FKBP12-Tie2 knockout mice, whereas an isotype control had no effect. Augmenting regulatory T cells and inhibiting interleukin-17 signaling using noncellular therapies prevents the cardiovascular and renal toxicity of calcineurin inhibitors in mice. © 2017 American Heart Association, Inc.

Direct Reprogramming of Human Bone Marrow Stromal Cells into Functional Renal Cells Using Cell-free Extracts

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Evangelia Papadimou

2015-04-01

Full Text Available The application of cell-based therapies in regenerative medicine is gaining recognition. Here, we show that human bone marrow stromal cells (BMSCs, also known as bone-marrow-derived mesenchymal cells, can be reprogrammed into renal proximal tubular-like epithelial cells using cell-free extracts. Streptolysin-O-permeabilized BMSCs exposed to HK2-cell extracts underwent morphological changes—formation of “domes” and tubule-like structures—and acquired epithelial functional properties such as transepithelial-resistance, albumin-binding, and uptake and specific markers E-cadherin and aquaporin-1. Transmission electron microscopy revealed the presence of brush border microvilli and tight intercellular contacts. RNA sequencing showed tubular epithelial transcript abundance and revealed the upregulation of components of the EGFR pathway. Reprogrammed BMSCs integrated into self-forming kidney tissue and formed tubular structures. Reprogrammed BMSCs infused in immunodeficient mice with cisplatin-induced acute kidney injury engrafted into proximal tubuli, reduced renal injury and improved function. Thus, reprogrammed BMSCs are a promising cell resource for future cell therapy.

Renal tissue alterations were size-dependent with smaller ones induced more effects and related with time exposure of gold nanoparticles

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Jarrar Bashir M

2011-09-01

Full Text Available Abstract Background Gold nanoparticles (GNPs have important application for cell labeling and imaging, drug delivery, diagnostic and therapeutic purposes mainly in cancer. Nanoparticles (NPs are being increasingly exploited for medical applications. The aim of the present study was to investigate the particle-size and period effects of administration of GNPs on the renal tissue in an attempt to address their potential toxicity. Methods A total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 μl of GNPs infusion of size (10, 20 and 50 nm for 3 or 7 days to investigate particle-size effect of GNPs on the renal tissue. Animals were randomly divided into groups, 6 GNPs-treated rats groups and one control group. Groups 1, 2 and 3 received infusion of 50 μl GNPs of size 10 nm (3 or 7 days, size 20 nm (3 or 7 days and 50 nm (3 or 7 days, respectively; while groups 4, 5 and 6 received infusion of 100 μl GNPs of size 10 nm, size 20 nm and 50 nm, respectively. Stained sections of control and treated rats kidneys were examined for renal tissue alterations induced by GNPs. Results In comparison with respective control rats, exposure to GNPs doses has produced the following renal tubular alterations: cloudy swelling, vacuolar degeneration, hyaline droplets and casts, anisokaryosis, karopyknosis, karyorrhexis and karyolysis. The glomeruli showed moderate congestion with no hypercelluraity, mesangial proliferation or basement membrane thickening. The histological alterations were mainly seen in the cortex and the proximal renal convoluted tubules were more affected than the distal ones. Conclusions The induced histological alterations might be an indication of injured renal tubules due to GNPs toxicity that became unable to deal with the accumulated residues resulting from metabolic and structural disturbances caused by these NPs. The findings may suggest that GNPs interact with proteins and enzymes of the renal tissue

Is renal medullary carcinoma the seventh nephropathy in sickle cell ...

African Journals Online (AJOL)

Introduction: Previous studies had enlisted renal medullary carcinoma (RMC) as the seventh nephropathy in sickle cell disease (SCD). Clinical experience has contradicted this claim and this study is targeted at refuting or supporting this assumption. Objective: To estimate the prevalence of RMC and describe other renal ...

Renal cell tumors with clear cell histology and intact VHL and chromosome 3p: a histological review of tumors from the Cancer Genome Atlas database.

Science.gov (United States)

Favazza, Laura; Chitale, Dhananjay A; Barod, Ravi; Rogers, Craig G; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam; Gupta, Nilesh S; Williamson, Sean R

2017-11-01

Clear cell renal cell carcinoma is by far the most common form of kidney cancer; however, a number of histologically similar tumors are now recognized and considered distinct entities. The Cancer Genome Atlas published data set was queried (http://cbioportal.org) for clear cell renal cell carcinoma tumors lacking VHL gene mutation and chromosome 3p loss, for which whole-slide images were reviewed. Of the 418 tumors in the published Cancer Genome Atlas clear cell renal cell carcinoma database, 387 had VHL mutation, copy number loss for chromosome 3p, or both (93%). Of the remaining, 27/31 had whole-slide images for review. One had 3p loss based on karyotype but not sequencing, and three demonstrated VHL promoter hypermethylation. Nine could be reclassified as distinct or emerging entities: translocation renal cell carcinoma (n=3), TCEB1 mutant renal cell carcinoma (n=3), papillary renal cell carcinoma (n=2), and clear cell papillary renal cell carcinoma (n=1). Of the remaining, 6 had other clear cell renal cell carcinoma-associated gene alterations (PBRM1, SMARCA4, BAP1, SETD2), leaving 11 specimens, including 2 high-grade or sarcomatoid renal cell carcinomas and 2 with prominent fibromuscular stroma (not TCEB1 mutant). One of the remaining tumors exhibited gain of chromosome 7 but lacked histological features of papillary renal cell carcinoma. Two tumors previously reported to harbor TFE3 gene fusions also exhibited VHL mutation, chromosome 3p loss, and morphology indistinguishable from clear cell renal cell carcinoma, the significance of which is uncertain. In summary, almost all clear cell renal cell carcinomas harbor VHL mutation, 3p copy number loss, or both. Of tumors with clear cell histology that lack these alterations, a subset can now be reclassified as other entities. Further study will determine whether additional entities exist, based on distinct genetic pathways that may have implications for treatment.

mTOR inhibitors in the treatment of advanced renal cell carcinoma

International Nuclear Information System (INIS)

Barilla, R.; Sycova-Mila, Z.

2009-01-01

Renal Cell Carcinoma (RCC) accounts for approximately 4 % of all malignancies. Much is known about the pathogenesis of RCC because of studies examining its close relationship with dysfunction of the Von Hippel-Lindau gene (VHL) and hypoxia inducible factor (HIF). Mammalian target of rapamycin (mTOR) regulates nutritional needs, cell growth, and angiogenesisi in cells by down regulating or up regulating a variety of proteins including HIF. Until 2005, only a single agent high dose interleukin 2 was approved by Food and Drug Administration (FDA) for treatment of advanced renal cell carcinoma. More recently thanks to better knowledge in the field of molecular biology new treatment options appeared. Sunitinib and bevacizumab are currently considered to be treatment of first choice for patients in good and intermediate prognostic group and sorafenib is preferred second line treatment in the same patient population pretreated with cytokines after disease progression. Temsirolimus and everolimus, rapamycin analouges, have recently been tested in III trials in first and second line treatment in patients with advanced metastatic clear cell renal cell carcinoma. (author)

A new mouse model for renal lesions produced by intravenous injection of diphtheria toxin A-chain expression plasmid

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Nakamura Shingo

2004-04-01

Full Text Available Abstract Background Various animal models of renal failure have been produced and used to investigate mechanisms underlying renal disease and develop therapeutic drugs. Most methods available to produce such models appear to involve subtotal nephrectomy or intravenous administration of antibodies raised against basement membrane of glomeruli. In this study, we developed a novel method to produce mouse models of renal failure by intravenous injection of a plasmid carrying a toxic gene such as diphtheria toxin A-chain (DT-A gene. DT-A is known to kill cells by inhibiting protein synthesis. Methods An expression plasmid carrying the cytomegalovirus enhancer/chicken β-actin promoter linked to a DT-A gene was mixed with lipid (FuGENE™6 and the resulting complexes were intravenously injected into adult male B6C3F1 mice every day for up to 6 days. After final injection, the kidneys of these mice were sampled on day 4 and weeks 3 and 5. Results H-E staining of the kidney specimens sampled on day 4 revealed remarkable alterations in glomerular compartments, as exemplified by mesangial cell proliferation and formation of extensive deposits in glomerular basement membrane. At weeks 3 and 5, gradual recovery of these tissues was observed. These mice exhibited proteinuria and disease resembling sub-acute glomerulonephritis. Conclusions Repeated intravenous injections of DT-A expression plasmid DNA/lipid complex caused temporary abnormalities mainly in glomeruli of mouse kidney. The disease in these mice resembles sub-acute glomerulonephritis. These DT-A gene-incorporated mice will be useful as animal models in the fields of nephrology and regenerative medicine.

Cardiac Metastasis in Renal Cell Carcinoma

African Journals Online (AJOL)

abp

2015-10-21

Oct 21, 2015 ... Metastatic disease of the heart is over twenty times more common than primary heart tumors [1]. They are among the least known and highly debated issues in oncology, and few systematic studies are devoted to this topic. Cardiac involvement in renal cell carcinoma (RCC) commonly arises from direct ...

Regulatory mechanism of ulinastatin on autophagy of macrophages and renal tubular epithelial cells

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Wu Ming

2018-04-01

Full Text Available Kidney ischemia and hypoxia can cause renal cell apoptosis and activation of inflammatory cells, which lead to the release of inflammatory factors and ultimately result in the damage of kidney tissue and the whole body. Renal tubular cell and macrophage autophagy can reduce the production of reactive oxygen species (ROS, thereby reducing the activation of inflammatory cytoplasm and its key effector protein, caspase-1, which reduces the expression of IL-1β and IL-18 and other inflammatory factors. Ulinastatin (UTI, as a glycoprotein drug, inhibits the activity of multiple proteases and reduces myocardial damage caused by ischemia-reperfusion by upregulating autophagy. However, it can be raised by macrophage autophagy, reduce the production of ROS, and ultimately reduce the expression of inflammatory mediators, thereby reducing renal cell injury, promote renal function recovery is not clear. In this study, a series of cell experiments have shown that ulinastatin is reduced by regulating the autophagy of renal tubular epithelial cells and macrophages to reduce the production of reactive oxygen species and inflammatory factors (TNF-α, IL-1β and IL-1, and then, increase the activity of the cells under the sugar oxygen deprivation model. The simultaneous use of cellular autophagy agonists Rapamycin (RAPA and ulinastatin has a synergistic effect on the production of reactive oxygen species and the expression of inflammatory factors.

Concurrent Multilocular Cystic Renal Cell Carcinoma and Leiomyoma in the Same Kidney: Previously Unreported Association

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Min Su Cheong

2010-07-01

Full Text Available We present an unusual case of concurrent occurrence of a multilocular cystic renal cell carcinoma and a leiomyoma in the same kidney of a patient with no evident clinical symptoms. A 38-year-old man was found incidentally to have a cystic right renal mass on computed tomography. Laparoscopic radical nephrectomy was performed under a preoperative diagnosis of cystic renal cell carcinoma. Histology revealed a multilocular cystic renal cell carcinoma and a leiomyoma. This is the first report of this kind of presentation.

T-cell Responses in the Microenvironment of Primary Renal Cell Carcinoma-Implications for Adoptive Cell Therapy

DEFF Research Database (Denmark)

Andersen, Rikke; Westergaard, Marie Christine Wulff; Kjeldsen, Julie Westerlin

2018-01-01

In vitro expansion of large numbers of highly potent tumor-reactive T cells appears a prerequisite for effective adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TIL) as shown in metastatic melanoma (MM). We therefore sought to determine whether renal cell carcinomas (RCC...

Cell-metal interactions: A comparison of natural uranium to other common metals in renal cells and bone osteoblasts

International Nuclear Information System (INIS)

Milgram, S.; Carriere, M.; Thiebault, C.; Berger, P.; Khodja, H.; Gouget, B.

2007-01-01

Uranium acute intoxication has been documented to induce nephrotoxicity. Kidneys are the main target organs after short term exposures to high concentrations of the toxic, while chronic exposures lead to its accumulation in the skeleton. In this paper, chemical toxicity of uranium is investigated for rat osteoblastic bone cells and compared to results previously obtained on renal cells. We show that bone cells are less sensitive to uranium than renal cells. The influence of the chemical form on U cytotoxicity is demonstrated. For both cell types, a comparison of uranium toxicity with other metals or metalloids toxicities (Mn, Ni, Co, Cu, Zn, Se and Cd) permits classification of Cd, Zn, Se IV and Cu as the most toxic and Ni, Se VI , Mn and U as the least toxic. Chemical toxicity of natural uranium proves to be far less than that of cadmium. To try to explain the differences in sensitivities observed between metals and different cell types, cellular accumulations in cell monolayers are quantified by inductively coupled plasma-mass spectroscopy (ICP-MS), function of time or function of dose: lethal doses which simulate acute intoxications and sub-lethal doses which are more realistic with regard to environmentally metals concentrations. In addition to being more resistant, bone cells accumulated much more uranium than did renal cells. Moreover, for both cell models, Mn, U-citrate and U-bicarbonate are strongly accumulated whereas Cu, Zn and Ni are weakly accumulated. On the other hand, a strong difference in Cd behaviour between the two cell types is shown: whereas Cd is very weakly accumulated in bone cells, it is very strongly accumulated in renal cells. Finally, elemental distribution of the toxics is determined on a cellular scale using nuclear microprobe analysis. For both renal and osteoblastic cells, uranium was accumulated in as intracellular precipitates similar to those observed previously by SEM/EDS

Cell-metal interactions: A comparison of natural uranium to other common metals in renal cells and bone osteoblasts

Energy Technology Data Exchange (ETDEWEB)

Milgram, S. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Carriere, M. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Thiebault, C. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Berger, P. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Khodja, H. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France); Gouget, B. [Laboratoire Pierre Suee, CEA-CNRS UMR 9956, CEA/Saclay, 91191 Gif-sur-Yvette (France)]. E-mail: barbara.gouget@cea.fr

2007-07-15

Uranium acute intoxication has been documented to induce nephrotoxicity. Kidneys are the main target organs after short term exposures to high concentrations of the toxic, while chronic exposures lead to its accumulation in the skeleton. In this paper, chemical toxicity of uranium is investigated for rat osteoblastic bone cells and compared to results previously obtained on renal cells. We show that bone cells are less sensitive to uranium than renal cells. The influence of the chemical form on U cytotoxicity is demonstrated. For both cell types, a comparison of uranium toxicity with other metals or metalloids toxicities (Mn, Ni, Co, Cu, Zn, Se and Cd) permits classification of Cd, Zn, Se{sup IV} and Cu as the most toxic and Ni, Se{sup VI}, Mn and U as the least toxic. Chemical toxicity of natural uranium proves to be far less than that of cadmium. To try to explain the differences in sensitivities observed between metals and different cell types, cellular accumulations in cell monolayers are quantified by inductively coupled plasma-mass spectroscopy (ICP-MS), function of time or function of dose: lethal doses which simulate acute intoxications and sub-lethal doses which are more realistic with regard to environmentally metals concentrations. In addition to being more resistant, bone cells accumulated much more uranium than did renal cells. Moreover, for both cell models, Mn, U-citrate and U-bicarbonate are strongly accumulated whereas Cu, Zn and Ni are weakly accumulated. On the other hand, a strong difference in Cd behaviour between the two cell types is shown: whereas Cd is very weakly accumulated in bone cells, it is very strongly accumulated in renal cells. Finally, elemental distribution of the toxics is determined on a cellular scale using nuclear microprobe analysis. For both renal and osteoblastic cells, uranium was accumulated in as intracellular precipitates similar to those observed previously by SEM/EDS.

Renal Protective Effects of Low Molecular Weight of Inonotus obliquus Polysaccharide (LIOP on HFD/STZ-Induced Nephropathy in Mice

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Yen-Jung Chou

2016-09-01

Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage renal disease in diabetes mellitus. Oxidative stress, insulin resistance and pro-inflammatory cytokines have been shown to play an important role in pathogeneses of renal damage on type 2 diabetes mellitus (DM. Inonotus obliquus (IO is a white rot fungus that belongs to the family Hymenochaetaceae; it has been used as an edible mushroom and exhibits many biological activities including anti-tumor, anti-oxidant, anti-inflammatory and anti-hyperglycemic properties. Especially the water-soluble Inonotus obliquus polysaccharides (IOPs have been previously reported to significantly inhibit LPS-induced inflammatory cytokines in mice and protect from streptozotocin (STZ-induced diabetic rats. In order to identify the nephroprotective effects of low molecular weight of IOP fraction (LIOP, from the fruiting bodies of Inonotus obliquus, high-fat diet (HFD plus STZ-induced type 2-like diabetic nephropathy C57BL/6 mice were investigated in this study. Our data showed that eight weeks of administration of 10–100 kDa, LIOP (300 mg/kg had progressively increased their sensitivity to glucose (less insulin tolerance, reduced triglyceride levels, elevated the HDL/LDL ratio and decreased urinary albumin/creatinine ratio(ACR compared to the control group. By pathological and immunohistochemical examinations, it was indicated that LIOP can restore the integrity of the glomerular capsules and increase the numbers of glomerular mesangial cells, associated with decreased expression of TGF-β on renal cortex in mice. Consistently, three days of LIOP (100 μg/mL incubation also provided protection against STZ + AGEs-induced glucotoxicity in renal tubular cells (LLC-PK1, while the levels of NF-κB and TGF-β expression significantly decreased in a dose-dependent manner. Our findings demonstrate that LIOP treatment could ameliorate glucolipotoxicity-induced renal fibrosis, possibly partly via the inhibition of NF

Development of a wearable bioartificial kidney using the Bioartificial Renal Epithelial Cell System (BRECS).

Science.gov (United States)

Johnston, Kimberly A; Westover, Angela J; Rojas-Pena, Alvaro; Buffington, Deborah A; Pino, Christopher J; Smith, Peter L; Humes, H David

2017-11-01

Cell therapy for the treatment of renal failure in the acute setting has proved successful, with therapeutic impact, yet development of a sustainable, portable bioartificial kidney for treatment of chronic renal failure has yet to be realized. Challenges in maintaining an anticoagulated blood circuit, the typical platform for solute clearance and support of the biological components, have posed a major hurdle in advancement of this technology. This group has developed a Bioartificial Renal Epithelial Cell System (BRECS) capable of differentiated renal cell function while sustained by body fluids other than blood. To evaluate this device for potential use in end-stage renal disease, a large animal model was established that exploits peritoneal dialysis fluid for support of the biological device and delivery of cell therapy while providing uraemic control. Anephric sheep received a continuous flow peritoneal dialysis (CFPD) circuit that included a BRECS. Sheep were treated with BRECS containing 1 × 10 8 renal epithelial cells or acellular sham devices for up to 7 days. The BRECS cell viability and activity were maintained with extracorporeal peritoneal fluid circulation. A systemic immunological effect of BRECS therapy was observed as cell-treated sheep retained neutrophil oxidative activity better than sham-treated animals. This model demonstrates that use of the BRECS within a CFPD circuit embodies a feasible approach to a sustainable and effective wearable bioartificial kidney. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Preparation of positional renal slices for study of cell-specific toxicity.

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Ruegg, C E; Gandolfi, A J; Nagle, R B; Krumdieck, C L; Brendel, K

1987-04-01

To reduce structural complexity, rabbit kidneys were sliced perpendicular to their cortical-papillary axis to isolate four distinct cell groupings. This positional orientation allows identification of each renal cell type based on its location within the slice. A mechanical slicer was used to make several precision-cut slices rapidly from an oriented cylindrical core of renal tissue, with minimal tissue trauma. Slices were then submerged under a gently circulating oxygenated media in a fritted glass support system that maintains viability (intracellular K+/DNA ratio) and structural integrity (histology) for at least 30 h. A high dose of mercuric chloride (10(-3) M) was used to demonstrate the structural and biochemical changes of intoxicated slices. This method provides a controlled subchronic in vitro system for the study of the individual cell types involved in cell-specific renal toxicities and may also be a useful tool for addressing other pharmacological and physiological research questions.

Secondary renal amyloidosis in a patient of pulmonary tuberculosis and common variable immunodeficiency

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Balwani Manish R

2015-04-01

Full Text Available Common variable immunodeficiency (CVID usually manifests in the second or third decade of life with recurrent bacterial infections and hypoglobulinemia. Secondary renal amyloidosis with history of pulmonary tuberculosis is rare in CVID, although T cell dysfunction has been reported in few CVID patients. A 40-year-old male was admitted to our hospital with a 3-month history of recurrent respiratory infections and persistent pitting pedal edema. His past history revealed 3 to 5 episodes of recurrent respiratory tract infections and diarrhoea each year since last 20 years. He had been successfully treated for sputum positive pulmonary tuberculosis 8 years back. Laboratory studies disclosed high erythrocyte sedimentation rate (ESR, hypoalbuminemia and nephrotic range proteinuria. Serum immunoglobulin levels were low. CD4/CD8 ratio and CD3 level was normal. C3 and C4 complement levels were normal. Biopsy revealed amyloid A (AA positive secondary renal amyloidosis. Glomeruli showed variable widening of mesangial regions with deposition of periodic schiff stain (PAS pale positive of pink matrix showing apple green birefringence on Congo-red staining. Immunohistochemistry was AA stain positive. Immunofluorescence microscopy revealed no staining with anti-human IgG, IgM, IgA, C3, C1q, kappa and lambda light chains antisera. Patient was treated symptomatically for respiratory tract infection and was discharged with low dose angiotensin receptor blocker. An old treated tuberculosis and chronic inflammation due to recurrent respiratory tract infections were thought to be responsible for AA amyloidosis. Thus pulmonary tuberculosis should be considered in differential diagnosis of secondary causes of AA renal amyloidosis in patients of CVID especially in endemic settings.

Microwave treatment of renal cell carcinoma adjacent to renal sinus.

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Gao, Yongyan; Liang, Ping; Yu, Xiaoling; Yu, Jie; Cheng, Zhigang; Han, Zhiyu; Duan, Shaobo; Huang, Hui

2016-11-01

To evaluate the efficacy and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for renal cell carcinoma (RCC) adjacent to renal sinus. This retrospective study included 41 patients who underwent US-guided percutaneous MWA of 41 RCCs adjacent to the renal sinus from April 2006 to December 2015. Contrast-enhanced images of US and computed tomography (CT) or magnetic resonance (MR) imaging were performed at pre-ablation and 1day, 1 month, 3 months, and every 6 months after ablation. Initial ablation success (IAS), disease-free survival (DFS), RCC-related survival (RRS), and overall survival (OS) were recorded at the follow-up visits. IAS was achieved in 92.7% (38/41) of the study subjects. The IAS significantly differed between patients with RCCs ≤4cm (100%, 29/29) and RCCs >4cm (75%, 9/12, p=0.021). During the median follow-up of 37.6 (range, 3.0-97.3) months, the estimated 1-, 3-, and 5-year DFS of patients with an initial tumor of ≤4cm were 100%, 89.7%, and 81.5%, respectively. The 1-, 3-, and 5-year RRS were 100%, 93.3%, and 93.3%, respectively. The 1-, 3-, and 5-year OS were 97.1%, 87.8%, and 83.6%, respectively. The multivariate analysis using the Cox proportional hazard model revealed no independent predictor of recurrence among all the variables. There were no MWA-related deaths among the study subjects. One patient developed a retroperitoneal abscess after ablation. US-guided percutaneous MWA appears to be a promising method for RCCs adjacent to renal sinus, especially for tumors ≤4cm. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Combined blockade of angiotensin II and prorenin receptors ameliorates podocytic apoptosis induced by IgA-activated mesangial cells.

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Leung, Joseph C K; Chan, Loretta Y Y; Saleem, M A; Mathieson, P W; Tang, Sydney C W; Lai, Kar Neng

2015-07-01

Glomerulo-podocytic communication plays an important role in the podocytic injury in IgA nephropathy (IgAN). In this study, we examine the role of podocytic angiotensin II receptor subtype 1 (AT1R) and prorenin receptor (PRR) in podocytic apoptosis in IgAN. Polymeric IgA (pIgA) was isolated from patients with IgAN and healthy controls. Conditioned media were prepared from growth arrested human mesangial cells (HMC) incubated with pIgA from patients with IgAN (IgA-HMC media) or healthy controls (Ctl-HMC media). A human podocyte cell line was used as a model to examine the regulation of the expression of AT1R, PRR, TNF-α and CTGF by IgA-HMC media. Podocytic nephrin expression, annexin V binding and caspase 3 activity were used as the functional readout of podocytic apoptosis. IgA-HMC media had no effect on AngII release by podocytes. IgA-HMC media significantly up-regulated the expression of AT1R and PRR, down-regulated nephrin expression and induced apoptosis in podocytes. Mono-blockade of AT1R, PRR, TNF-α or CTGF partially reduced podocytic apoptosis. IgA-HMC media activated NFκB, notch1 and HEY1 expression by podocytes and dual blockade of AT1R with PRR, or anti-TNF-α with anti-CTGF, effectively rescued the podocytic apoptosis induced by IgA-HMC media. Our data suggests that pIgA-activated HMC up-regulates the expression of AT1R and PRR expression by podocytes and the associated activation of NFκB and notch signalling pathways play an essential role in the podocytic apoptosis induced by glomerulo-podocytic communication in IgAN. Simultaneously targeting the AT1R and PRR could be a potential therapeutic option to reduce the podocytic injury in IgAN.

Heavy metals toxicity after acute exposure of cultured renal cells. Intracellular accumulation and repartition

International Nuclear Information System (INIS)

Khodja, Hicham; Carriere, Marie; Avoscan, Laure; Gouget, Barbara

2005-01-01

Lead (Pb), cadmium (Cd) and uranium (U) present no known biological function but are toxic in various concentration ranges. Pb and Cd lead generally to nephrotoxicity consisting in proximal renal tubular dysfunction and accumulation while U has been reported to induce chemical kidney toxicity, functional and histological damages being as well mainly observed in proximal tubule cells. This work address the question of Cd, Pb, and U cytotoxicity, intracellular accumulation and repartition after acute intoxication of renal proximal tubule epithelial cells. After cells exposure to different concentrations of metals for various times, morphological changes were observed and intracellular concentrations and distributions of toxic metals were specified by PIXE coupled to RBS. Cell viability, measured by biochemical tests, was used as toxicity indicator. A direct correlation between cytotoxicity and intracellular accumulation in renal epithelial cells have been established. Finally, intracellular Pb and U localizations were detected while Cd was found to be uniformly distributed in renal cells. (author)

Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

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Tokiko Ishida

Full Text Available The pathogenesis of renal impairment in chronic liver diseases (CLDs has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy, autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the

Long-term response to nivolumab and acute renal failure in a patient with metastatic papillary renal-cell carcinoma and a PD-L1 tumor expression increased with sunitinib therapy: A case report.

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Juan Ruiz-Bañobre

2016-11-01

Full Text Available Introduction: Papillary renal-cell carcinoma, which represents around 20% of renal cell carcinomas, is a heterogeneous disease that includes different tumor types with several clinical and molecular phenotypes. Nivolumab, a fully human IgG4 programmed cell death protein 1 immune checkpoint inhibitor antibody, has shown not only an overall survival advantage when compared to everolimus, but also a relatively good side-effect profile among patients with previously treated advanced or metastatic renal-cell carcinoma. Case report: We describe a case of a young man diagnosed with papillary renal-cell carcinoma that achieved a durable response to nivolumab despite a temporary suspension of the treatment due to a renal function side effect. To our knowledge, it is the first renal failure secondary to nivolumab in a metastatic renal-cell carcinoma patient.Concluding Remarks: Nivolumab is a promising drug in patients with metastatic papillary renal-cell carcinoma and long-term responses can be achieved. In case of acute renal failure secondary to this treatment, temporary therapy suspension and a low dose of systemic corticosteroids can recover renal function without a negative impact on treatment efficacy.

Percutaneous and laparoscopic assisted cryoablation of small renal cell carcinomas

DEFF Research Database (Denmark)

Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Borre, Michael

Aim: To evaluate the complication rate and short term oncological outcome of small renal cell carcinomas treated with cryoablation. Materials and methods: 91 biopsy verified renal cell carcinomas were cryoablated between 2006-11. Patients treated had primarily T1a tumors, but exceptions were made...... Medical® was used. Treatment was considered successful when tumors gradually shrunk and showed no sign of contrast enhancement, assessed by CT or MRI. Results: Mean patient age and tumor size was 65 yr [17 - 83] and 26 mm [10 - 62], respectively [min-max]. Treatment modalities consisted of percutaneous...

Metastatic Renal Cell Carcinoma to Jejunum: An Unusual Case Presentation

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Igor Medic

2017-07-01

Full Text Available The small intestine is a very uncommon and peculiar site for metastasis from renal cell carcinoma (RCC. We present a clinical presentation of insidious and unusual development of a jejunal metastasis while having stable disease in a remainder of metastatic sites, in a patient undergoing immunotherapy with nivolumab. Due to the extreme rarity of metastatic renal cell carcinoma to the lumen of the small bowel, it is easy to overlook and misdiagnose symptoms of this pathologic entity, particularly when the remainder of metastatic disease responds well to ongoing therapy.

Magnetic resonance imaging in the staging of renal cell carcinoma

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Kishi, Hiroichi; Umeda, Takashi; Niijima, Tadao; Yashiro, Naobumi; Kawabe, Kazuki

1987-07-01

Eighteen patients with renal neoplasm underwent magnetic resonance imaging (MRI) using a 1.5 Tesla superconducting magnetic system and spin echo images were obtained by quick scan technique under holding breath. MR images were interpreted independently of the computerized tomography (CT) findings. The preoperative stagings of the 18 renal carcinomas, as judged by MRI, were compared with those obtained at laparotomy. The anatomic staging was correctly performed by MRI in 13 patients (72 %). In the patients who had intrarenal small tumor with normal renal contour, MRI demonstrated a solid mass clearly distinguishable from surrounding renal parenchyma using the paramagnetic contrast agent (gadolinium-DTPA). When compared with results of evaluation by CT in staging, MRI appeared to have several advantages in determination of whole mass; the detection of tumor thrombus into renal vein and inferior vena cava; and the evaluation of direct tumor invasion of adjacent organs. MRI should play an important role in the staging of renal cell carcinoma.

Magnetic resonance imaging in the staging of renal cell carcinoma

International Nuclear Information System (INIS)

Kishi, Hiroichi; Umeda, Takashi; Niijima, Tadao; Yashiro, Naobumi; Kawabe, Kazuki

1987-01-01

Eighteen patients with renal neoplasm underwent magnetic resonance imaging (MRI) using a 1.5 Tesla superconducting magnetic system and spin echo images were obtained by quick scan technique under holding breath. MR images were interpreted independently of the computerized tomography (CT) findings. The preoperative stagings of the 18 renal carcinomas, as judged by MRI, were compared with those obtained at laparotomy. The anatomic staging was correctly performed by MRI in 13 patients (72 %). In the patients who had intrarenal small tumor with normal renal contour, MRI demonstrated a solid mass clearly distinguishable from surrounding renal parenchyma using the paramagnetic contrast agent (gadolinium-DTPA). When compared with results of evaluation by CT in staging, MRI appeared to have several advantages in determination of whole mass; the detection of tumor thrombus into renal vein and inferior vena cava; and the evaluation of direct tumor invasion of adjacent organs. MRI should play an important role in the staging of renal cell carcinoma. (author)

[Knockdown of ATG5 enhances the sensitivity of human renal carcinoma cells to sunitinib].

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Li, Peng; Han, Qi; Tang, Ming; Zhang, Keqin

2017-03-01

Objective To investigate the expression levels of autophagy-related gene 5 (ATG5) and microtubule-associated protein 1 light chain 3 (LC3) and their effects on sunitinib resistance in human renal carcinoma cells. Methods After clinic-pathologic feature and survival analysis, 99 renal clear cell carcinoma tissues with different histological grades were used to detect the expression of ATG5 and LC3 by immunohistochemistry. Renal carcinoma cell line A-498 was infected with lentivirus-mediated ATG5 shRNA. Western blot analysis was performed to confirm the efficiency of ATG5 knockdown. Proliferation rate of A-498 cells in control group and ATG5 low expression group was determined by flow cytometry. Finally, the survival rate was detected by MTT assay after A-498 cells were treated with different concentrations of sunitinib. Results The expression levels of ATG5 and LC3 in renal clear cell carcinoma tissues were significantly higher than those in para-tumor tissues. The expression levels of ATG5 and LC3 were associated with classification, histological grade, TNM stage and survival rate, rather than gender, age, location, tumor size. Compared with the control group, the protein expressions of ATG5 and LC3 significantly decreased in A-498 cells with ATG5 low expression. The cell proliferation rate in ATG5 downregulation group was lower than that in the control group. Compared with control group, the survival rate in ATG5 low expression group were significantly reduced in a dose-dependent manner after sunitinib treatment. Conclusion Autophagy is active in renal clear cell carcinoma, and the drug sensitivity to sunitinib in renal cancer cells can be enhanced by the downregulation of ATG5.

Not all renal stem cell niches are the same: anatomy of an evolution

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Clara Gerosa

2016-08-01

Full Text Available The renal stem cell niche represents the most important structure of the developing kidney, responsible for nephrogenesis. Recently, some Authors have reported, at ultrastructural level, a previously unknown complexity of the architecture of renal stem cell niche in experimental models. This study was aimed at studying, at histological level, the anatomy of renal stem cell niches in the human fetal kidney. To this end, ten fetal kidneys, whose gestational ages ranged from 11 up to 24 weeks, were studied. H&E-stained sections were observed at high power. The study of the anatomy of renal stem cell niches in the human kidney revealed a previously unreported complexity: some niches appeared as a roundish arrangement of mesenchymal cells; others showed the initial phases of induction by ureteric buds; in other niches the process of mesenchymal epithelial transition was more evident; finally, in other stem cell niches the first signs of nephron origin were detectable. These findings suggest the existence of niches with different anatomy in the same kidney, indicating different stages of evolution even in adjacent niches. All stem cell niches were in strict contact with the capsular cells, suggesting a major role of the renal capsule in nephrogenesis. Finally, our study confirms the existence of a strict contact between the bud tip cells and the surrounding mesenchyme in the human developing kidney, giving a morphological support to the theory of intercellular channels allowing the passage of transcription factors from the epithelial to the mesenchymal stem/progenitors cells.Proceedings of the 2nd International Course on Perinatal Pathology (part of the 11th International Workshop on Neonatology · October 26th-31st, 2015 · Cagliari (Italy · October 31st, 2015 · Stem cells: present and future Guest Editors: Gavino Faa, Vassilios Fanos, Antonio Giordano

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

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Christopher J. Ricketts

2018-04-01

Full Text Available Summary: Renal cell carcinoma (RCC is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD ChRCC that associated with extremely poor survival. : Ricketts et al. find distinctive features of each RCC subtype, providing the foundation for development of subtype-specific therapeutic and management strategies. Somatic alteration of BAP1, PBRM1, and metabolic pathways correlates with subtype-specific decreased survival, while CDKN2A alteration, DNA hypermethylation, and Th2 immune signature correlate with decreased survival within all subtypes. Keywords: clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma, CDKN2A, DNA hypermethylation, immune signature, chromatin remodeling, TCGA, PanCanAtlas

Epithelial-Mesenchymal Transition in Kidney Tubular Epithelial Cells Induced by Globotriaosylsphingosine and Globotriaosylceramide.

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Yeo Jin Jeon

Full Text Available Fabry disease is a lysosomal storage disorder caused by deficiency of alpha-galactosidase A (α-gal A, which results in the deposition of globotriaosylceramide (Gb3 in the vascular endothelium. Globotriaosylsphingosine (lyso-Gb3, a deacylated Gb3, is also increased in the plasma of patients with Fabry disease. Renal fibrosis is a key feature of advanced Fabry disease patients. Therefore, we evaluated the association of Gb3 and lyso-Gb3 accumulation and the epithelial-mesenchymal transition (EMT on tubular epithelial cells of the kidney. In HK2 cells, exogenous treatments of Gb3 and lyso-Gb3 increased the expression of TGF-β, EMT markers (N-cadherin and α-SMA, and phosphorylation of PI3K/AKT, and decreased the expression of E-cadherin. Lyso-Gb3, rather than Gb3, strongly induced EMT in HK2 cells. In the mouse renal mesangial cell line, SV40 MES 13 cells, Gb3 strongly induced phenotype changes. The EMT induced by Gb3 was inhibited by enzyme α-gal A treatment, but EMT induced by lyso-Gb3 was not abrogated by enzyme treatment. However, TGF-β receptor inhibitor (TRI, SB525334 inhibited the activation of TGF-β and EMT markers in HK2 cells with Gb3 and lyso-Gb3 treatments. This study suggested that increased plasma lyso-Gb3 has a crucial role in the development of renal fibrosis through the cell-specific induction of the EMT in Fabry disease, and that TRI treatment, alongside enzyme replacement therapy, could be a potential therapeutic option for patients with Fabry disease.

Resveratrol promotes regression of renal carcinoma cells via a renin-angiotensin system suppression-dependent mechanism.

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Li, Jianchang; Qiu, Mingning; Chen, Lieqian; Liu, Lei; Tan, Guobin; Liu, Jianjun

2017-02-01

The aim of the present study was to investigate the effect of resveratrol on renal carcinoma cells and explore possible renin-angiotensin system-associated mechanisms. Subsequent to resveratrol treatment, the cell viability, apoptosis rate, cytotoxicity levels, caspase 3/7 activity and the levels of angiotensin II (AngII), AngII type 1 receptor (AT1R), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) were evaluated in renal carcinoma cells. The effects of AngII, AT1R, VEGF and COX-2 on resveratrol-induced cell growth inhibition and apoptosis were also examined. The results indicated that resveratrol treatment may suppress growth, induce apoptosis, and decrease AngII, AT1R, VEGF and COX-2 levels in renal carcinoma ACHN and A498 cells. In addition, resveratrol-induced cell growth suppression and apoptosis were reversed when co-culturing with AT1R or VEGF. Thus, resveratrol may suppress renal carcinoma cell proliferation and induce apoptosis via an AT1R/VEGF pathway.

Renal type a intercalated cells contain albumin in organelles with aldosterone-regulated abundance.

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Thomas Buus Jensen

Full Text Available Albumin has been identified in preparations of renal distal tubules and collecting ducts by mass spectrometry. This study aimed to establish whether albumin was a contaminant in those studies or actually present in the tubular cells, and if so, identify the albumin containing cells and commence exploration of the origin of the intracellular albumin. In addition to the expected proximal tubular albumin immunoreactivity, albumin was localized to mouse renal type-A intercalated cells and cells in the interstitium by three anti-albumin antibodies. Albumin did not colocalize with markers for early endosomes (EEA1, late endosomes/lysosomes (cathepsin D or recycling endosomes (Rab11. Immuno-gold electron microscopy confirmed the presence of albumin-containing large spherical membrane associated bodies in the basal parts of intercalated cells. Message for albumin was detected in mouse renal cortex as well as in a wide variety of other tissues by RT-PCR, but was absent from isolated connecting tubules and cortical collecting ducts. Wild type I MDCK cells showed robust uptake of fluorescein-albumin from the basolateral side but not from the apical side when grown on permeable support. Only a subset of cells with low peanut agglutinin binding took up albumin. Albumin-aldosterone conjugates were also internalized from the basolateral side by MDCK cells. Aldosterone administration for 24 and 48 hours decreased albumin abundance in connecting tubules and cortical collecting ducts from mouse kidneys. We suggest that albumin is produced within the renal interstitium and taken up from the basolateral side by type-A intercalated cells by clathrin and dynamin independent pathways and speculate that the protein might act as a carrier of less water-soluble substances across the renal interstitium from the capillaries to the tubular cells.

The effects of renal transplantation on circulating dendritic cells

NARCIS (Netherlands)

D.A. Hesselink (Dennis); L.M.B. Vaessen (Leonard); W.C.J. Hop (Wim); W. Schoordijk-Verschoor (Wenda); J.N.M. IJzermans (Jan); C.C. Baan (Carla); W. Weimar (Willem)

2005-01-01

textabstractThe effects of immunosuppressive agents on T cell function have been well characterized but virtually nothing is known about the effects of renal transplantation on human dendritic cells (DCs). With the use of flow cytometry, we studied the kinetics of myeloid and plasmacytoid DCs in

Application of modified R.E.N.A.L. nephrometry score system in evaluating the retroperitoneal partial nephrectomy for T1 renal cell carcinoma.

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Wang, Qinzhang; Qian, Biao; Li, Qiang; Ni, Zhao; Li, Yinglong; Wang, Xinmin

2015-01-01

This study aims to investigate the application of the modified R.E.N.A.L. nephrometry score system in evaluating the operation difficulty of retroperitoneal partial nephrectomy in T1 renal cell carcinoma patients. A total of 52 patients with T1 renal cell carcinoma were enrolled. They all had retroperitoneal partial nephrectomy. Their clinical data was retrospectively analyzed. R.E.N.A.L. nephrometry score system was modified based on the features of retroperitoneal partial nephrectomy. The specificity, sensitivity and Youden index were compared between R.E.N.A.L. nephrometry score system and the modified R.E.N.A.L. nephrometry score system. The effect of the modified R.E.N.A.L. nephrometry score system on perioperative outcomes was analyzed. Three degrees of operation difficulty were defined by the modified R.E.N.A.L. nephrometry score system, which included the low, medium and high degree of operation difficulty. The specificity, sensitivity and Youden index of the modified R.E.N.A.L. nephrometry score system were better than those of the original R.E.N.A.L. nephrometry score system. Compared with low degree of operation difficulty, patients with medium and high degree of operation difficulty had significantly higher levels of operative time, warm ischemia time, and intraoperative blood loss (P system has a good effect in evaluating the operation difficulty of retroperitoneal partial nephrectomy.

Wnt Signaling in Renal Cell Carcinoma

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Qi Xu

2016-06-01

Full Text Available Renal cell carcinoma (RCC accounts for 90% of all kidney cancers. Due to poor diagnosis, high resistance to the systemic therapies and the fact that most RCC cases occur sporadically, current research switched its focus on studying the molecular mechanisms underlying RCC. The aim is the discovery of new effective and less toxic anti-cancer drugs and novel diagnostic markers. Besides the PI3K/Akt/mTOR, HGF/Met and VHL/hypoxia cellular signaling pathways, the involvement of the Wnt/β-catenin pathway in RCC is commonly studied. Wnt signaling and its targeted genes are known to actively participate in different biological processes during embryonic development and renal cancer. Recently, studies have shown that targeting this pathway by alternating/inhibiting its intracellular signal transduction can reduce cancer cells viability and inhibit their growth. The targets and drugs identified show promising potential to serve as novel RCC therapeutics and prognostic markers. This review aims to summarize the current status quo regarding recent research on RCC focusing on the involvement of the Wnt/β-catenin pathway and how its understanding could facilitate the identification of potential therapeutic targets, new drugs and diagnostic biomarkers.

IgG4-related tubulointerstitial nephritis with plasma cell-rich renal arteritis.

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Sharma, Shree G; Vlase, Horia L; D'Agati, Vivette D

2013-04-01

Immunoglobulin G4 (IgG4)-related tubulointerstitial nephritis is a newly recognized clinicopathologic entity that may occur as an isolated renal lesion or as part of a multisystem disorder. It is characterized by plasma cell-rich interstitial nephritis with abundant IgG4-positive plasma cells and IgG-dominant tubulointerstitial immune deposits. We report the first case of IgG4-related tubulointerstitial nephritis with multifocal plasma cell-rich renal arteritis presenting as acute kidney injury in a 72-year-old man. Seven weeks of prednisone therapy led to nearly complete recovery of kidney function. This case enlarges the morphologic spectrum of this disorder and emphasizes the need to distinguish it from other causes of renal vasculitis. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Cell therapy in renal and cardiovascular disease Terapia celular en enfermedades renales y cardiovasculares

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Juan Manuel Senior Sánchez

2006-01-01

Full Text Available Although there have been important advances in the field of molecular biology, the mechanisms responsible for nephrogenesis and the factors that modulate the process of development, proliferation, growth, and maturation during fetal and adult life have not been thoroughly explained. Animals, including mammals, share the intrinsic ability to regenerate tissues and organs as an important biological defense mechanism. In the case of the kidney, after tissue damage secondary to injury, anatomical and functional recovery of integrity is achieved, accompanied by the activation of a complex, poorly understood process, leading to the replacement of damaged tubular cells by functional ones that reorganize tubular architecture. This regeneration and repair process is produced by somatic, exogenous, adult stem cells, and probably by intrinsic renal stem cells, that are responsible for maintaining renal homeostasis Aunque se han logrado grandes avances en el campo de la biología molecular, todavía no se han esclarecido completamente los mecanismos responsables de la organogénesis y los factores que modulan el proceso de desarrollo, proliferación, crecimiento y maduración celulares durante la vida fetal y adulta. Los animales comparten la capacidad de regenerar tejidos y órganos, como un mecanismo biológico importante de defensa. En el caso del riñón, luego del daño tisular secundario a una noxa, se produce recuperación anatómica y funcional de la integridad, acompañada por la activación de un proceso sofisticado, mal comprendido, que lleva al reemplazo de las células tubulares dañadas por otras funcionalmente normales que reorganizan la arquitectura tubular. Este fenómeno de recambio se produce gracias a la presencia de células madre adultas somáticas exógenas, responsables del proceso de mantenimiento de la homeostasis renal, y posiblemente por células renales intrínsecas.

Metallothionein gene expression in renal cell carcinoma

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Deeksha Pal

2014-01-01

Full Text Available Introduction: Metallothioneins (MTs are a group of low-molecular weight, cysteine-rich proteins. In general, MT is known to modulate three fundamental processes: (1 the release of gaseous mediators such as hydroxyl radical or nitric oxide, (2 apoptosis and (3 the binding and exchange of heavy metals such as zinc, cadmium or copper. Previous studies have shown a positive correlation between the expression of MT with invasion, metastasis and poor prognosis in various cancers. Most of the previous studies primarily used immunohistochemistry to analyze localization of MT in renal cell carcinoma (RCC. No information is available on the gene expression of MT2A isoform in different types and grades of RCC. Materials and Methods: In the present study, total RNA was isolated from 38 histopathologically confirmed cases of RCC of different types and grades. Corresponding adjacent normal renal parenchyma was taken as control. Real-time polymerase chain reaction (RT PCR analysis was done for the MT2A gene expression using b-actin as an internal control. All statistical calculations were performed using SPSS software. Results: The MT2A gene expression was found to be significantly increased (P < 0.01 in clear cell RCC in comparison with the adjacent normal renal parenchyma. The expression of MT2A was two to three-fold higher in sarcomatoid RCC, whereas there was no change in papillary and collecting duct RCC. MT2A gene expression was significantly higher in lower grade (grades I and II, P < 0.05, while no change was observed in high-grade tumor (grade III and IV in comparison to adjacent normal renal tissue. Conclusion: The first report of the expression of MT2A in different types and grades of RCC and also these data further support the role of MT2A in tumorigenesis.

Combined effect of angioinfarction with immunotherapy in patients with stage IV renal cell carcinoma

International Nuclear Information System (INIS)

Oh, Joo Hyeong; Yoon, Yup; Jeong, Yu Mee; Ko, Young Tae; Chang, Sung Goo

1994-01-01

To assess the combined effectiveness of angioinfarction and immunotherapy for improving survival in patients with stage IV renal cell carcinoma. During the past 3 years, 13 patients of stage IV renal cell carcinoma were treated with angioinfarction and immunotherapy. Angioinfarction was performed on these 13 patients using absolute ethanol and occlusive balloon catheter. After angioinfarction, Interferon alpha was used for immunotherapy. For our analysis, 12 control patients of stage IV renal cell carcinoma without treatment were included in the study. Survival has been calculated according to the Kaplan and Meier method. The 1 year survival rate and median survival time in patients treated with angioinfarction and immunotherapy, were 46% and 13 months and in patients without treatment, 16% and 4 months, respectively. The combined treatment of angioinfarction and immunotherapy is of considerable value for improving survival in patients with stage IV renal cell carcinoma

Cancers as wounds that do not heal: differences and similarities between renal regeneration/repair and renal cell carcinoma.

Science.gov (United States)

Riss, Joseph; Khanna, Chand; Koo, Seongjoon; Chandramouli, Gadisetti V R; Yang, Howard H; Hu, Ying; Kleiner, David E; Rosenwald, Andreas; Schaefer, Carl F; Ben-Sasson, Shmuel A; Yang, Liming; Powell, John; Kane, David W; Star, Robert A; Aprelikova, Olga; Bauer, Kristin; Vasselli, James R; Maranchie, Jodi K; Kohn, Kurt W; Buetow, Ken H; Linehan, W Marston; Weinstein, John N; Lee, Maxwell P; Klausner, Richard D; Barrett, J Carl

2006-07-15

Cancers have been described as wounds that do not heal, suggesting that the two share common features. By comparing microarray data from a model of renal regeneration and repair (RRR) with reported gene expression in renal cell carcinoma (RCC), we asked whether those two processes do, in fact, share molecular features and regulatory mechanisms. The majority (77%) of the genes expressed in RRR and RCC were concordantly regulated, whereas only 23% were discordant (i.e., changed in opposite directions). The orchestrated processes of regeneration, involving cell proliferation and immune response, were reflected in the concordant genes. The discordant gene signature revealed processes (e.g., morphogenesis and glycolysis) and pathways (e.g., hypoxia-inducible factor and insulin-like growth factor-I) that reflect the intrinsic pathologic nature of RCC. This is the first study that compares gene expression patterns in RCC and RRR. It does so, in particular, with relation to the hypothesis that RCC resembles the wound healing processes seen in RRR. However, careful attention to the genes that are regulated in the discordant direction provides new insights into the critical differences between renal carcinogenesis and wound healing. The observations reported here provide a conceptual framework for further efforts to understand the biology and to develop more effective diagnostic biomarkers and therapeutic strategies for renal tumors and renal ischemia.

Suture Granuloma Mimicking Renal Cell Carcinoma: Magnetic Resonance Imaging (MRI and Pathologic Correlation

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İbrahim İlker Öz

2014-11-01

Full Text Available Solid renal masses are generally distinguished with contrast enhancement and intratumoral fatty foci by radiological examinations. The present of enhancement is most important criteria for diagnosis of malignant lesions. Generally, a contrast enhanced solid mass in kidney is accepted as a neoplasm. Foreign body granuloma is an extraordinary cause of enhanced solid renal mass. This case of a renal suture granuloma demonstrated peripheral enhanced exophytic renal mass mimic renal cell carcinoma, and underwent surgery. At the solid renal mass with different radiological features, biopsy is an option to determining the necessity of surgery as well as the surgical approach.

Radiofrequency ablation of renal cell carcinoma under CT guidance. Present and Future status

International Nuclear Information System (INIS)

Nasu, Yasutomo; Kobayashi, Yasuyuki; Uematsu, Katsutoshi; Saika, Takashi; Kumon, Hiromi; Gohara, Hideo; Mimura, Hidefumi; Kanazawa, Susumu

2011-01-01

At Okayama University, radiofrequency ablation (RFA) of renal cell carcinoma was performed in May 2002 as the initial case in Japan. In 2004, it was regarded as an advanced medical technique by the Japanese authority. Since then, RFA has been actively performed for renal cell carcinoma not only at the primary site but also at the metastatic site, including the lung and bone. The clinical outcome has been compatible with other institutes and no serious adverse events have occurred. From the view paint of fusing technical innovation with medical safety, this treatment is a potent therapeutic option for renal cell carcinoma. In the era of laparoscopic surgery, RFA is indicated for cases with von Hippel-Lindau disease (VHL), recurrence after partial nephrectomy, a single kidney and intolerance to general anesthesia, due to its technical advantage in that RFA can be repeated. In this review, the current clinical outcome is reported and future prospects are discussed as to whether it can be the safest and most concrete treatment for renal cell carcinoma in the 21 st century. (author)

Evaluation of resectability of renal cell carcinoma by computed tomography

International Nuclear Information System (INIS)

Hiramatsu, Yoshihiro; Matsumoto, Kunihiko; Tatezawa, Takashi; Kikuchi, Yoichi; Akisada, Masahiro; Kitagawa, Ryuichi

1982-01-01

Renal cell carcinoma is one of the unique neoplasm which is characterized by disappearing of the metastatic tumors after removal of the primary lesion. Angiography has been performed to evaluate the resectability of the primary tumor by nephrectomy in the past. With the use of computed tomography, detailed evaluation of the retroperitoneal structures is now possible. We have evaluated the resectability of renal cell tumor by computed tomography and compared the results with the angiographic findings and operative findings. Computed tomography is very accurate in determining the extent of the tumor especially in evaluation of tumor and the Gerota's fascia, which is essential to determine the resectability of the tumor. Informations about lymph node metastasis and invasion to the renal veins or inferior vena cava are also obtained.FIn most of the cases, angiography can be spared if computed tomography is properly performed. (author)

Imaging features of renal complications after crizotinib treatment for non–small-cell lung cancer: a case report

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Wan Ying Chan, MBBS

2016-09-01

Full Text Available Crizotinib has been approved for the treatment of advanced ALK-positive non–small cell lung cancer. Its use is associated with the development of complex renal cysts. However, there is limited literature regarding imaging features of renal cystic disease during crizotinib therapy and its complications or progression. Here, we describe a case of a patient with ALK-positive advanced non–small cell lung cancer who developed complex renal cyst during crizotinib treatment. The renal cyst is complicated by infection and abscess formation. Subsequent renal biopsy, antibiotics treatment, and open drainage of loculated renal abscess showed no malignant cells and contributed to the diagnosis. The imaging features should be recognized as renal cystic disease of crizotinib treatment and not to be mistaken as new metastasis and disease progression.

Combination of active components of Xiexin decoction ameliorates renal fibrosis through the inhibition of NF-κB and TGF-β1/Smad pathways in db/db diabetic mice.

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Jia-Sheng Wu

Full Text Available Xiexin decoction, a herbal therapeutic agent commonly used in traditional Chinese medicine, is recognized for its beneficial effects on diabetic nephropathy exerted through the combined action of multiple components, including Rhizoma Coptidis alkaloids (A, Radix et Rhizoma Rhei polysaccharides (P, and Radix Scutellaria flavones (F. Our previous studies have shown that a combination of A, P, and F (APF exhibits renoprotective effects against diabetic nephropathy. This study was aimed at determining the effects of APF on renal fibrosis in diabetic nephropathy and elucidating the underlying molecular mechanisms. To evaluate the effects of APF, in vivo, db/db diabetic mice were orally administered a low or high dose of APF (300 or 600 mg/kg, respectively once a day for 8 weeks. We evaluated the blood and urine indices of metabolic and renal function, renal tissue histopathology, renal inflammation, and fibrosis. APF treatment significantly ameliorated glucose and lipid metabolism dysfunction, decreased urinary albumin excretion, normalized creatinine clearance, and reduced the morphological changes in renal tissue. Additionally, APF administration in db/db diabetic mice reduced the elevated levels of renal inflammation mediators such as intercellular adhesion molecule-1, monocyte chemotactic protein-1, tumor necrosis factor-α, interleukin-1β, and active nuclear factor κB (NF-κB. APF treatment also reduced type I and IV collagen, transforming growth factor-β1 (TGF-β1, and TGF-β1 type II receptor expression levels, and decreased the phosphorylation of Smad2/3 in the kidneys of db/db diabetic mice. These results suggest that APF reduces renal fibrosis in diabetic nephropathy through the NF-κB and TGF-β1/Smad signaling pathways. In vitro, APF treatment reduced cell proliferation and protein expression of α-smooth muscle actin, collagen I, TGF-β1 and NF-κB in mesangial cells cultured with high glucose concentrations. Our findings indicate

Choroid plexus metastasis of renal-cell carcinoma. A case report

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Shigemori, Minoru; Shimamoto, Houtetsu; Noguchi, Shinji; Yoshitake, Yasuhiro; Sugita, Yasuo; Kuramoto, Shinken

1987-10-01

A rare case of the choroid plexus metastasis of renal-cell carcinoma is reported. A 58-year-old man was admitted on March 3, 1982, with complaints of mild headache and a transient attack of muscle weakness of the left upper extremity. He had undergone a left nephrectomy because of renal-cell carcinoma 2 years before this admission. A CT scan revealed a small mass in the right lateral ventricle that was markedly enhanced by the contrast medium. A carotid angiogram was normal, but a left vertebral angiogram showed a round tumor stain in the distal portion of the right posterior choroidal artery. To determine the nature of the tumor, it was successfully removed via the right frontal transventricular approach. The immediate recovery from the operation was uneventful, but the patient became semicomatose 6 hours later because of a large subdural hematoma over the left hemisphere. An emergency operation for clot removal and external decompression failed to improve the patient's status, and he died on the 3rd postoperative day. An histological examination of the tumor determined the diagnosis of clear-cell-type renal-cell carcinoma. The CT demonstration of choroid plexus metastasis is quite rare. To our knowledge, only two cases have been described.

Tumor-promoting phorbol esters effect alkalinization of canine renal proximal tubular cells

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Mellas, J.; Hammerman, M.R.

1986-01-01

We have demonstrated the presence of specific receptors for tumor-promoting phorbol esters in the plasma membrane of the canine renal proximal tubular cell. These compounds affect proximal tubular metabolism in vitro. For example, we have shown that they inhibit gluconeogenesis in canine renal proximal tubular segments. Tumor-promoting phorbol esters have been shown to effect alkalinization of non-renal cells, by enhancing Na + -H + exchange across the plasma membrane. To determine whether the actions of tumor-promoting phorbol esters in proximal tubular segments might be mediated by a similar process, we incubated suspensions of segments from dog kidney with these compounds and measured changes in intracellular pH using [ 14 C]-5,5-dimethoxazoladine-2-4-dione (DMO) and flow dialysis. Incubation of segments with phorbol 12,13 dibutyrate, but not inactive phorbol ester, 4 γ phorbol, effected alkalinization of cells within the segments in a concentration-dependent manner. Alkalinization was dependent upon the presence of extracellular [Na + ] > intracellular [Na + ], was prevented by amiloride and was demonstrable in the presence of SITS. Our findings suggest that tumor-promoting esters stimulate the Na + -H + exchanger known to be present in the brush border membrane of the renal proximal tubular cell. It is possible that the stimulation reflects a mechanism by which phorbol esters affect metabolic processes in these cells

Renal Replacement Therapy in End-Stage Sickle Cell Nephropathy: Presentation of Two Cases and Literature Review

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Al-Mueilo, Samir H.

2005-01-01

Chronic renal failure develops in 4-18% of patients with sickle cell anemia. Hemodialysis and kidney transplant are viable options in the management of end-stage renal disease in patients with sickle cell diseases (SCD). Information on kidney disease among Saudi patients with SCD is non-existing. In this report, the clinical course of two adult males with end-stage sickle cell nephropathy from Eastern Saudi Arabia is described. Literature on renal replacement therapy in sickle cell anemia (SCA) is discussed. (author)

Angiotensin-(1-7 relieved renal injury induced by chronic intermittent hypoxia in rats by reducing inflammation, oxidative stress and fibrosis

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W. Lu

Full Text Available We aimed to study the renal injury and hypertension induced by chronic intermittent hypoxia (CIH and the protective effects mediated by angiotensin 1-7 [Ang(1-7]. We randomly assigned 32 male Sprague-Dawley rats (body weight 180-200 g to normoxia control, CIH, Ang(1-7-treated normoxia, and Ang(1-7-treated CIH groups. Systolic blood pressure (SBP was monitored at the start and end of each week. Renal sympathetic nerve activity (RSNA was recorded. CTGF and TGF-β were detected by immunohistochemistry and western blotting. Tissue parameters of oxidative stress were also determined. In addition, renal levels of interleukin-6, tumor necrosis factor-α, nitrotyrosine, and hypoxia-inducible factor-1α were determined by immunohistochemistry, immunoblotting, and ELISA. TUNEL assay results and cleaved caspase 3 and 12 were also determined. Ang(1-7 induced a reduction in SBP together with a restoration of RSNA in the rat model of CIH. Ang(1-7 treatment also suppressed the production of reactive oxygen species, reduced renal tissue inflammation, ameliorated mesangial expansion, and decreased renal fibrosis. Thus, Ang(1-7 treatment exerted renoprotective effects on CIH-induced renal injury and was associated with a reduction of oxidative stress, inflammation and fibrosis. Ang(1-7 might therefore represent a promising therapy for obstructive sleep apnea-related hypertension and renal injury.

Ischiogluteal bursitis mimicking soft-tissue metastasis from a renal cell carcinoma

International Nuclear Information System (INIS)

Voelk, M.; Gmeinwieser, J.; Manke, C.; Strotzer, M.; Hanika, H.

1998-01-01

We report a case of ischiogluteal bursitis mimicking a soft-tissue metastasis from a renal cell carcinoma. A 66-year-old woman suffered from pain over the left buttock 6 months after she was operated on for renal cell carcinoma of the left kidney. CT of the abdomen and pelvis revealed a tumor-like lesion adjacent to the left os ischii, which was suspected to be a soft-tissue metastasis. Percutaneous biopsy revealed no evidence of malignancy, but the histopathological diagnosis of chronic bursitis. (orig.)

Involvement of caspase-12-dependent apoptotic pathway in ionic radiocontrast urografin-induced renal tubular cell injury

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Wu, Cheng Tien [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Weng, Te I. [Department of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Chen, Li Ping [Department of Dentistry, Chang Gang Memorial Hospital, Chang Gang University, Taoyuan, Taiwan (China); Chiang, Chih Kang [Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Liu, Shing Hwa, E-mail: shinghwaliu@ntu.edu.tw [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China)

2013-01-01

Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This toxic effect subjects in the disorder of CM-induced nephropathy. Our previous work has demonstrated that CM shows to activate the endoplasmic reticulum (ER)-related adaptive unfolding protein response (UPR) activators. Glucose-regulated protein 78 (GRP78)/eukaryotic initiation factor 2α (eIF2α)-related pathways play a protective role during the urografin (an ionic CM)-induced renal tubular injury. However, the involvement of ER stress-related apoptotic signals in the urografin-induced renal tubular cell injury remains unclear. Here, we examined by the in vivo and in vitro experiments to explore whether ER stress-regulated pro-apoptotic activators participate in urografin-induced renal injury. Urografin induced renal tubular dilation, tubular cells detachment, and necrosis in the kidneys of rats. The tubular apoptosis, ER stress-related pro-apoptotic transcriptional factors, and kidney injury marker-1 (kim-1) were also conspicuously up-regulated in urografin-treated rats. Furthermore, treatment of normal rat kidney (NRK)-52E tubular cells with urografin augmented the expressions of activating transcription factor-6 (ATF-6), C/EBP homologous protein (CHOP), Bax, caspase-12, JNK, and inositol-requiring enzyme (IRE) 1 signals. Urografin-induced renal tubular cell apoptosis was not reversed by the inhibitors of ATF-6, JNK signals or CHOP siRNA transfection, but it could be partially reversed by the inhibitor of caspase-12. Taken together, the present results and our previous findings suggest that exposure of CM/urografin activates the ER stress-regulated survival- and apoptosis-related signaling pathways in renal tubular cells. Caspase-12-dependent apoptotic pathway may be partially involved in the urografin-induced nephropathy. -- Highlights: ► Ionic contrast medium-urografin induces renal tubular cell apoptosis. ► Urografin induces the ER stress-regulated survival and apoptosis

Gonadal vein tumor thrombosis due to renal cell carcinoma

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Hamidreza Haghighatkhah

2015-01-01

Full Text Available Renal cell carcinoma (RCC had a tendency to extend into the renal vein and inferior vena cava, while extension into the gonadal vein has been rarely reported. Gonadal vein tumor thrombosis appears as an enhancing filling defect within the dilated gonadal vein anterior to the psoas muscle and shows an enhancement pattern identical to that of the original tumor. The possibility of gonadal vein thrombosis should be kept in mind when looking at an imaging study of patients with RCC

Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice.

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Hitomi, Hirofumi; Kasahara, Tomoko; Katagiri, Naoko; Hoshina, Azusa; Mae, Shin-Ichi; Kotaka, Maki; Toyohara, Takafumi; Rahman, Asadur; Nakano, Daisuke; Niwa, Akira; Saito, Megumu K; Nakahata, Tatsutoshi; Nishiyama, Akira; Osafune, Kenji

2017-09-27

The production of erythropoietin (EPO) by the kidneys, a principal hormone for the hematopoietic system, is reduced in patients with chronic kidney disease (CKD), eventually resulting in severe anemia. Although recombinant human EPO treatment improves anemia in patients with CKD, returning to full red blood cell production without fluctuations does not always occur. We established a method to generate EPO-producing cells from human induced pluripotent stem cells (hiPSCs) by modifying previously reported hepatic differentiation protocols. These cells showed increased EPO expression and secretion in response to low oxygen conditions, prolyl hydroxylase domain-containing enzyme inhibitors, and insulin-like growth factor 1. The EPO protein secreted from hiPSC-derived EPO-producing (hiPSC-EPO) cells induced the erythropoietic differentiation of human umbilical cord blood progenitor cells in vitro. Furthermore, transplantation of hiPSC-EPO cells into mice with CKD induced by adenine treatment improved renal anemia. Thus, hiPSC-EPO cells may be a useful tool for clarifying the mechanisms of EPO production and may be useful as a therapeutic strategy for treating renal anemia. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Iodine quantification to distinguish clear cell from papillary renal cell carcinoma at dual-energy multidetector CT: a multireader diagnostic performance study.

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Mileto, Achille; Marin, Daniele; Alfaro-Cordoba, Marcela; Ramirez-Giraldo, Juan Carlos; Eusemann, Christian D; Scribano, Emanuele; Blandino, Alfredo; Mazziotti, Silvio; Ascenti, Giorgio

2014-12-01

To investigate whether dual-energy multidetector row computed tomographic (CT) imaging with iodine quantification is able to distinguish between clear cell and papillary renal cell carcinoma ( RCC renal cell carcinoma ) subtypes. In this retrospective, HIPAA-compliant, institutional review board-approved study, 88 patients (57 men, 31 women) with diagnosis of either clear cell or papillary RCC renal cell carcinoma at pathologic analysis, who underwent contrast material-enhanced dual-energy nephrographic phase study between December 2007 and June 2013, were included. Five readers, blinded to pathologic diagnosis, independently evaluated all cases by determining the lesion iodine concentration on color-coded iodine maps. The receiving operating characteristic curve analysis was adopted to estimate the optimal threshold for discriminating between clear cell and papillary RCC renal cell carcinoma , and results were validated by using a leave-one-out cross-validation. Interobserver agreement was assessed by using an intraclass correlation coefficient. The correlation between tumor iodine concentration and tumor grade was investigated. A tumor iodine concentration of 0.9 mg/mL represented the optimal threshold to discriminate between clear cell and papillary RCC renal cell carcinoma , and it yielded the following: sensitivity, 98.2% (987 of 1005 [95% confidence interval: 97.7%, 98.7%]); specificity, 86.3% (272 of 315 [95% confidence interval: 85.0%, 87.7%]); positive predictive value, 95.8% (987 of 1030 [95% confidence interval: 95.0%, 96.6%]); negative predictive value, 93.7% (272 of 290 [95% confidence interval: 92.8%, 94.7%]); overall accuracy of 95.3% (1259 of 1320 [95% confidence interval: 94.6%, 96.2%]), with an area under the curve of 0.923 (95% confidence interval: 0.913, 0.933). An excellent agreement was found among the five readers in measured tumor iodine concentration (intraclass correlation coefficient, 0.9990 [95% confidence interval: 0. 9987, 0.9993). A

Vitamin E Intake and Risk of Renal Cell Carcinoma: A Meta-Analysis of 7 Case-Control Studies.

Science.gov (United States)

Shang, Yonggang; Yi, Shanhong; Cui, Dong; Han, Guangwei; Liu, Chengcheng

2015-07-01

Vitamin E intake may reduce the risk of renal cell carcinoma, but the results were inconsistent. Hence, we conducted a meta-analysis to assess the association between dietary vitamin E intake and the risk of renal cell carcinoma. We searched PubMed to identify the relevant case-control studies up to June 2014. Reference lists of retrieved articles were also reviewed. Odds ratios and corresponding 95% confidence intervals were used to estimate the association between dietary vitamin E intake and the risk of renal cell carcinoma. We identified 7 case-control studies regarding dietary vitamin E intake and risk of renal cell carcinoma, involving 5789 cases and 14866 controls. The odds ratio of renal cell carcinoma for the highest compared with the lowest dietary vitamin E intake was 0.75 (95% confidence interval: 0.59-0.91), and heterogeneity was observed across studies. The association between dietary vitamin E intake and the risk of renal cell carcinoma was not significantly differed by gender, but this association were inconsistent in the North American and European populations. Our study provided a evidence that there was a significant inverse association of dietary vitamin E intake with risk of renal cell carcinoma. However, this finding was based on the case-control studies, more well-designed cohort studies are needed. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Cutaneous metastasis of bilateral renal cell carcinoma.

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Abbasi, Fariba; Alizadeh, Mansur; Noroozinia, Farahnaz; Moradi, Amin

2013-01-01

Renal cell carcinoma (RCC) is a malignant lethal tumour with high potential of metastasis. However, metastasis from RCC to the skin is much less common. It is virtually a sign of poor prognosis. We represent a 42 years old man with bilateral RCC of clear cell type followed by metastasis to the scalp one month later. In this case the relatively young age of the patient, bilaterality of RCC and occurance of skin metastasis in the absence of recurrent kidney tumour are interesting.

The entire miR-200 seed family is strongly deregulated in clear cell renal cell cancer compared to the proximal tubular epithelial cells of the kidney

NARCIS (Netherlands)

Duns, Gerben; van den Berg, Anke; van Dijk, Marcory C. R. F.; van Duivenbode, Inge; Giezen, Cor; Kluiver, Joost; van Goor, Harry; Hofstra, Robert M. W.; van den Berg, Eva; Kok, Klaas

Despite numerous studies reporting deregulated microRNA (miRNA) and gene expression patterns in clear cell renal cell carcinoma (ccRCC), no direct comparisons have been made to its presumed normal counterpart: the renal proximal tubular epithelial cells (PTECs). The aim of this study was to

Computed tomography findings of pancreatic metastases from renal cell carcinoma

International Nuclear Information System (INIS)

Prando, Adilson

2008-01-01

Objective: To present computed tomography findings observed in four patients submitted to radical nephrectomy for renal cell carcinoma who developed pancreatic metastases afterwards. Materials and methods: The four patients underwent radical nephrectomy for stage Tz1 (n=2) and stage T3a (n=2) renal cell carcinoma. The mean interval between nephrectomy and detection of pancreatic metastases was eight years. Two asymptomatic patients presented with solitary pancreatic metastases (confined to the pancreas). Two symptomatic patients presented with single and multiple pancreatic metastases, both with tumor recurrence in the contralateral kidney. Results: Computed tomography studies demonstrated pancreatic metastases as solitary (n=2), single (n=1) or multiple (n=1) hypervascular lesions. Partial pancreatectomy was performed in two patients with solitary pancreatic metastases and both are free of disease at four and two years after surgery. Conclusion: Pancreatic metastases from renal cell carcinoma are rare and can occur many years after the primary tumor presentation. Multiple pancreatic metastases and pancreatic metastases associated with tumor recurrence in the contralateral kidney are uncommon. Usually, on computed tomography images pancreatic metastases are visualized as solitary hypervascular lesions, simulating isletcell tumors. Surgical management should be considered for patients with solitary pancreatic lesions. (author)

Computed tomography findings of pancreatic metastases from renal cell carcinoma

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Prando, Adilson [Hospital Vera Cruz, Campinas, SP (Brazil). Dept. of Radiology and Imaging Diagnosis]. E-mail: adilson.prando@gmail.com

2008-07-15

Objective: To present computed tomography findings observed in four patients submitted to radical nephrectomy for renal cell carcinoma who developed pancreatic metastases afterwards. Materials and methods: The four patients underwent radical nephrectomy for stage Tz1 (n=2) and stage T3a (n=2) renal cell carcinoma. The mean interval between nephrectomy and detection of pancreatic metastases was eight years. Two asymptomatic patients presented with solitary pancreatic metastases (confined to the pancreas). Two symptomatic patients presented with single and multiple pancreatic metastases, both with tumor recurrence in the contralateral kidney. Results: Computed tomography studies demonstrated pancreatic metastases as solitary (n=2), single (n=1) or multiple (n=1) hypervascular lesions. Partial pancreatectomy was performed in two patients with solitary pancreatic metastases and both are free of disease at four and two years after surgery. Conclusion: Pancreatic metastases from renal cell carcinoma are rare and can occur many years after the primary tumor presentation. Multiple pancreatic metastases and pancreatic metastases associated with tumor recurrence in the contralateral kidney are uncommon. Usually, on computed tomography images pancreatic metastases are visualized as solitary hypervascular lesions, simulating isletcell tumors. Surgical management should be considered for patients with solitary pancreatic lesions. (author)

Different Cytokine and Chemokine Expression Patterns in Malignant Compared to Those in Nonmalignant Renal Cells

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Nadine Gelbrich

2017-01-01

Full Text Available Objective. Cytokines and chemokines are widely involved in cancer cell progression and thus represent promising candidate factors for new biomarkers. Methods. Four renal cell cancer (RCC cell lines (Caki-1, 786-O, RCC4, and A498 and a nonmalignant renal cell line (RC-124 were examined with respect to their proliferation. The cytokine and chemokine expression pattern was examined by a DNA array (Human Cytokines & Chemokines RT2 Profiler PCR Array; Qiagen, Hilden, Germany, and expression profiles were compared. Results. Caki-1 and 786-O cells exhibited significantly increased proliferation rates, whereas RCC4 and A498 cells demonstrated attenuated proliferation, compared to nonmalignant RC-124 cells. Expression analysis revealed 52 cytokines and chemokines primarily involved in proliferation and inflammation and differentially expressed not only in malignant and nonmalignant renal cells but also in the four RCC cell lines. Conclusion. This is the first study examining the expression of 84 cytokines and chemokines in four RCC cell lines compared to that in a nonmalignant renal cell line. VEGFA, NODAL, and BMP6 correlated with RCC cell line proliferation and, thus, may represent putative clinical biomarkers for RCC progression as well as for RCC diagnosis and prognosis.

Diagnostic value of multidetector computed tomography for renal sinus fat invasion in renal cell carcinoma patients

International Nuclear Information System (INIS)

Kim, Cherry; Choi, Hyuck Jae; Cho, Kyoung-Sik

2014-01-01

Objective: Although renal sinus fat invasion has prognostic significance in patients with renal cell carcinomas (RCCs), there are no previous studies about the value of multidetector computed tomography (MDCT) about this issue in the current literature. Materials and methods: A total of 863 consecutive patients (renal sinus fat invasion in 110 patients (12.7%)) from single institutions with surgically-confirmed renal cell carcinoma who underwent MDCT between 2010 and 2012 were included in this study. The area under the curves (AUCs) of the receiver operating characteristic (ROC) analysis was used to compare diagnostic performance. Reference standard was pathologic examination. Weighted κ statistics were used to measure the level of interobserver agreement. Multivariate logistic regression model was used to find the predictors for renal sinus fat invasion. Image analysis was first performed with axial-only CT images. A second analysis was then performed with both axial and coronal CT images. A qualitative analysis was then conducted by two reviewers who reached consensus regarding tumor size, decreased perfusion, tumor margin, vessel displacement, and lymph node metastasis. The reference standard was pathologic evaluation. Results: The AUCs of the ROC analysis were 0.881 and 0.922 for axial-only images and 0.889 and 0.902 for combined images in both readers. The AUC of tumor size was 0.884, a similar value to that of the reviewers. In multivariate analysis, tumor size, a linear-nodular or nodular type of fat infiltration, and an irregular tumor margin were independent predicting factors for perinephric fat invasion. Conclusion: MDCT shows relatively high diagnostic performance in detecting perinephric fat invasion of RCC but suffers from a relatively low PPV related to low prevalence of renal sinus fat invasion. Applying tumor size alone we could get similar diagnostic performance to those of radiologists. Tumor size, fat infiltration with a nodular appearance, and

First-line sunitinib versus pazopanib in metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

DEFF Research Database (Denmark)

Ruiz-Morales, Jose Manuel; Swierkowski, Marcin; Wells, J Connor

2016-01-01

BACKGROUND: Sunitinib (SU) and pazopanib (PZ) are standards of care for first-line treatment of metastatic renal cell carcinoma (mRCC). However, how the efficacy of these drugs translates into effectiveness on a population-based level is unknown. PATIENTS AND METHODS: We used the International mR...

Ischiogluteal bursitis mimicking soft-tissue metastasis from a renal cell carcinoma

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Voelk, M.; Gmeinwieser, J.; Manke, C.; Strotzer, M. [Department of Radiology, University Hospital, Regensburg (Germany); Hanika, H. [Department of Urology, St. Josef Hospital, Regensburg (Germany)

1998-09-01

We report a case of ischiogluteal bursitis mimicking a soft-tissue metastasis from a renal cell carcinoma. A 66-year-old woman suffered from pain over the left buttock 6 months after she was operated on for renal cell carcinoma of the left kidney. CT of the abdomen and pelvis revealed a tumor-like lesion adjacent to the left os ischii, which was suspected to be a soft-tissue metastasis. Percutaneous biopsy revealed no evidence of malignancy, but the histopathological diagnosis of chronic bursitis. (orig.) With 2 figs., 8 refs.

Effects of hypercholesterolemia of renal hemodynamics: study in patients with nephrotic syndrome.

Science.gov (United States)

Fuiano, G; Esposito, C; Sepe, V; Colucci, G; Bovino, M; Rosa, M; Balletta, M; Bellinghieri, G; Conte, G; Cianciaruso, B; Dal Canton, A

1996-01-01

Experimental and clinical studies have demonstrated a positive relationship between hyperlipidemia and rate of progression of renal disease, suggesting that lipids can induce or aggravate glomerular injury mainly by interacting with mesangial cells. Nevertheless, recently has been demonstrated that increased cholesterol levels can also induce endothelial cell dysfunction. Thus, since endothelium is known to play a major role in modulating the vascular tone, we have tested the possibility that hypercholesterolemia impairs the renal hemodynamics in patients with active nephrotic syndrome and elevated serum cholesterol levels. In this single-blind, nonrandom study, 12 patients were treated with pravastatin (group T, treated, n = 12) and 8 with placebo (group C, controls, n = 8). The controls were studied after the pravastatin group had been completed. Before starting the treatment the patients underwent basal determinations including routine laboratory investigations and PAH and inulin clearances. The same determinations were repeated after 48 h, and 6 and 12 weeks from the beginning of the treatment. The study at 48 h was performed to see if pravastatin had a direct, cholesterol-independent effect on renal function. The following basal results were reported (mean +/- SEM; group T vs. group C): serum cholesterol (mmol/l) 9.7 +/- 0.4 vs. 9.1 +/- 0.3 (NS); proteinuria (g/24 h): 6.2 +/- 0.2 vs. 7.0 +/- 0.7 (NS); PAH clearance (ml/min): 353 +/- 21 vs. 385 +/- 31 (NS); inulin clearance (ml/min): 62.5 +/- 7.7 vs. 67 +/- 9.3 (NS). After 48 h, no changes were observed in both groups. Subsequently, in group T, the following percentage changes of basal levels were observed: serum cholesterol -21.4 +/- 3.2% at 6 weeks (p < 0.05) and -34.9 +/- 3.2% at 12 weeks (p < 0.01); inulin clearance +3 +/- 3.7% at 6 weeks (NS) and +9.3 +/- 2.9% at 12 weeks (p < 0.05); PAH clearance +7 +/- 3.1% at 6 weeks (p < 0.05) and +21.2 +/- 5.5% at 12 weeks (p < 0.01). By contrast, no significant

Previously unidentified changes in renal cell carcinoma gene expression identified by parametric analysis of microarray data

International Nuclear Information System (INIS)

Lenburg, Marc E; Liou, Louis S; Gerry, Norman P; Frampton, Garrett M; Cohen, Herbert T; Christman, Michael F

2003-01-01

Renal cell carcinoma is a common malignancy that often presents as a metastatic-disease for which there are no effective treatments. To gain insights into the mechanism of renal cell carcinogenesis, a number of genome-wide expression profiling studies have been performed. Surprisingly, there is very poor agreement among these studies as to which genes are differentially regulated. To better understand this lack of agreement we profiled renal cell tumor gene expression using genome-wide microarrays (45,000 probe sets) and compare our analysis to previous microarray studies. We hybridized total RNA isolated from renal cell tumors and adjacent normal tissue to Affymetrix U133A and U133B arrays. We removed samples with technical defects and removed probesets that failed to exhibit sequence-specific hybridization in any of the samples. We detected differential gene expression in the resulting dataset with parametric methods and identified keywords that are overrepresented in the differentially expressed genes with the Fisher-exact test. We identify 1,234 genes that are more than three-fold changed in renal tumors by t-test, 800 of which have not been previously reported to be altered in renal cell tumors. Of the only 37 genes that have been identified as being differentially expressed in three or more of five previous microarray studies of renal tumor gene expression, our analysis finds 33 of these genes (89%). A key to the sensitivity and power of our analysis is filtering out defective samples and genes that are not reliably detected. The widespread use of sample-wise voting schemes for detecting differential expression that do not control for false positives likely account for the poor overlap among previous studies. Among the many genes we identified using parametric methods that were not previously reported as being differentially expressed in renal cell tumors are several oncogenes and tumor suppressor genes that likely play important roles in renal cell

High Glucose Increases Metallothionein Expression in Renal Proximal Tubular Epithelial Cells

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Daisuke Ogawa

2011-01-01

Full Text Available Metallothionein (MT is an intracellular metal-binding, cysteine-rich protein, and is a potent antioxidant that protects cells and tissues from oxidative stress. Although the major isoforms MT-1 and -2 (MT-1/-2 are highly inducible in many tissues, the distribution and role of MT-1/-2 in diabetic nephropathy are poorly understood. In this study, diabetes was induced in adult male rats by streptozotocin, and renal tissues were stained with antibodies for MT-1/-2. MT-1/-2 expression was also evaluated in mProx24 cells, a mouse renal proximal tubular epithelial cell line, stimulated with high glucose medium and pretreated with the antioxidant vitamin E. MT-1/-2 expression was gradually and dramatically increased, mainly in the proximal tubular epithelial cells and to a lesser extent in the podocytes in diabetic rats, but was hardly observed in control rats. MT-1/-2 expression was also increased by high glucose stimulation in mProx24 cells. Because the induction of MT was suppressed by pretreatment with vitamin E, the expression of MT-1/-2 is induced, at least in part, by high glucose-induced oxidative stress. These observations suggest that MT-1/-2 is induced in renal proximal tubular epithelial cells as an antioxidant to protect the kidney from oxidative stress, and may offer a novel therapeutic target against diabetic nephropathy.

Incidental renal neoplasms

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Rabjerg, Maj; Mikkelsen, Minne Nedergaard; Walter, Steen

2014-01-01

On the basis of associations between tumor size, pathological stage, histological subtype and tumor grade in incidentally detected renal cell carcinoma vs symptomatic renal cell carcinoma, we discussed the need for a screening program of renal cell carcinoma in Denmark. We analyzed a consecutive...... series of 204 patients with renal tumors in 2011 and 2012. The tumors were classified according to detection mode: symptomatic and incidental and compared to pathological parameters. Eighty-nine patients (44%) were symptomatic, 113 (55%) were incidental. Information was not available in two patients...

Epidemiology, molecular epidemiology, and risk factors for renal cell carcinoma

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Chiara Paglino

2011-12-01

Full Text Available Despite only accounting for approximately 2% of all new primary cancer cases, renal cell carcinoma (RCC incidence has dramatically increased over time. Incidence rates vary greatly according to geographic areas, so that it is extremely likely that exogenous risk factors could play an important role in the development of this cancer. Several risk factors have been linked with RCC, including cigarette smoking, obesity, hypertension (and antihypertensive drugs, chronic kidney diseases (also dialysis and transplantation, as well as the use of certain analgesics. Furthermore, although RCC has not generally been considered an occupational cancer, several types of occupationally-derived exposures have been implicated in its pathogenesis. These include exposure to asbestos, chlorinated solvents, gasoline, diesel exhaust fumes, polycyclic aromatic hydrocarbons, printing inks and dyes, cadmium and lead. Finally, families with a predisposition to the development of renal neoplasms were identified and the genes involved discovered and characterized. Therefore, there are now four well-characterized, genetically determined syndromes associated with an increased incidence of kidney tumors, i.e., Von Hippel Lindau (VHL, Hereditary Papillary Renal Carcinoma (HPRC, Birt-Hogg-Dubé Syndrome (BHD, and Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC. This review will address present knowledge about the epidemiology, molecular epidemiology and risk factors of RCC.

Stem cells and their role in renal ischaemia reperfusion injury.

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Bagul, Atul; Frost, Jodie H; Drage, Martin

2013-01-01

Ischaemia-reperfusion injury (IRI) remains one of the leading causes of acute kidney injury (AKI). IRI is an underlying multifactorial pathophysiological process which affects the outcome in both native and transplanted patients. The high morbidity and mortality associated with IRI/AKI and disappointing results from current available clinical therapeutic approaches prompt further research. Stem cells (SC) are undifferentiated cells that can undergo both renewal and differentiation into one or more cell types which can possibly ameliorate IRI. To carry out a detailed literature analysis and construct a comprehensive literature review addressing the role of SC in AKI secondary to IRI. Evidence favouring the role of SC in renal IRI and evidence showing no benefits of SC in renal IRI are the two main aspects to be studied. The search strategy was based on an extensive search addressing MESH terms and free text terms. The majority of studies in the field of renal IRI and stem cell therapy show substantial benefits. Studies were mostly conducted in small animal models, thus underscoring the need for further pre-clinical studies in larger animal models, and results should be taken with caution. SC therapy may be promising though controversy exists in the exact mechanism. Thorough scientific exploration is required to assess mechanism, safety profile, reproducibility and methods to monitor administered SC. Copyright © 2012 S. Karger AG, Basel.

Erythrocytosis caused by giant chromophobe renal cell carcinoma: a case report indicating a 9-year misdiagnosis of polycythemia vera.

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Guo, Renbo; Liang, Yiran; Yan, Lei; Xu, Zhonghua; Ren, Juchao

2017-09-06

Erythrocytosis, a rare paraneoplastic syndrome, generally occurs in patients with clear cell renal cell carcinoma and has never been reported in patients with chromophobe renal cell carcinoma. We report a case of a young man suffering from a giant (22-cm) mass on his left kidney. Because of a history of polycythemia vera, the patient had been treated for the condition for 9 years. Radical nephrectomy was successfully performed, and the postoperative pathologic examination confirmed a diagnosis of chromophobe renal cell carcinoma. Unexpectedly, the symptom of erythrocytosis disappeared after the surgery. Further examination and analysis were performed, and we finally attributed his erythrocytosis to chromophobe renal cell carcinoma. Chromophobe renal cell carcinoma could cause erythrocytosis, but the clear-cut mechanism needs further research. Secondary erythrocytosis such as those related with renal tumors should be taken into consideration during the diagnosis of polycythemia vera.

The radiologist's role in the management of papillary renal cell carcinoma.

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Corral de la Calle, M Á; Encinas de la Iglesia, J; Martín López, M R; Fernández Pérez, G C; Águeda Del Bas, D S

Papillary carcinoma is the second most common renal cell carcinoma. It has a better prognosis than the more frequent clear cell carcinoma, although this does not hold true for advanced cases, because no specific treatment exists. It presents as a circumscribed peripheral tumor (small and homogeneously solid or larger and cystic/hemorrhagic) or as an infiltrating lesion that invades the veins, which has a worse prognosis. Due to their low vascular density, papillary renal cell carcinomas enhance less than other renal tumors, and this facilitates their characterization. On computed tomography, they might not enhance conclusively, and in these cases they are impossible to distinguish from hyperattenuating cysts. Contrast-enhanced ultrasonography and magnetic resonance imaging are more sensitive for detecting vascularization. Other characteristics include a specific vascular pattern, hypointensity on T2-weighted images, restricted water diffusion, and increased signal intensity in opposed phase images. We discuss the genetic, histologic, clinical, and radiological aspects of these tumors in which radiologists play a fundamental role in management. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Tubulocystic renal cell carcinoma: a new radiological entity

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Cornelis, F.; Grenier, N. [Pellegrin Hospital, Department of Radiology, Bordeaux (France); Helenon, O.; Correas, J.M. [Necker Hospital, Department of Radiology, Paris (France); Lemaitre, L. [Claude Huriez Hospital, Department of Radiology, Lille (France); Andre, M. [La-Conception Hospital, Department of Radiology, Marseille (France); Meuwly, J.Y. [Centre Hospitalier Universitaire Vaudois, Department of Radiology, Lausanne (Switzerland); Sengel, C. [Grenoble Hospital, Department of Radiology, Grenoble (France); Derchi, L. [Universita di Genova, Radiologia - DICMI, Genova (Italy); Yacoub, M. [Pellegrin Hospital, Department of Pathology, Bordeaux (France); Verkarre, V. [Necker Hospital, Department of Pathology, Paris (France)

2016-04-15

Tubulocystic renal cell carcinoma (TC-RCC) is a recently identified renal malignancy. While approximately 100 cases of TC-RCC have been reported in the pathology literature, imaging features have not yet been clearly described. The purpose of this review is to describe the main radiologic features of this rare sub-type of RCC on ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), based jointly on the literature and findings from a multi-institutional retrospective HIPAA-compliant review of pathology and imaging databases. Using a combination of sonographic and CT/MRI features, diagnosis of TC-RCC appeared to be strongly suggested in many cases. (orig.)

A Unique Presentation of an Undiagnosed Renal Cell Carcinoma

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Georgios Kravvas

2014-01-01

Full Text Available We describe a 58-year-old lady who presented initially to her general practitioner with a palpable warty urethral nodule. She was subsequently referred to the urology department for further investigations. She underwent flexible cystoscopy and imaging, followed by rigid cystoscopy and excision of the nodule. Histological analysis was consistent with renal cell carcinoma (RCC. CT imaging confirmed the presence of an invading metastatic left renal cell carcinoma with bilateral metastatic deposits to the lungs and adrenal glands. The patient was enlisted on the Panther Trial and received a course of Pazopanib before undergoing radical nephrectomy. Two years later she is still alive with metastases remaining reduced in size and numbers. During this study we have performed a literature review of similar cases with this unusual presentation of RCC.

Renal progenitor cells contribute to hyperplastic lesions of podocytopathies and crescentic glomerulonephritis.

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Smeets, Bart; Angelotti, Maria Lucia; Rizzo, Paola; Dijkman, Henry; Lazzeri, Elena; Mooren, Fieke; Ballerini, Lara; Parente, Eliana; Sagrinati, Costanza; Mazzinghi, Benedetta; Ronconi, Elisa; Becherucci, Francesca; Benigni, Ariela; Steenbergen, Eric; Lasagni, Laura; Remuzzi, Giuseppe; Wetzels, Jack; Romagnani, Paola

2009-12-01

Glomerular injury can involve excessive proliferation of glomerular epithelial cells, resulting in crescent formation and obliteration of Bowman's space. The origin of these hyperplastic epithelial cells in different glomerular disorders is controversial. Renal progenitors localized to the inner surface of Bowman's capsule can regenerate podocytes, but whether dysregulated proliferation of these progenitors contributes to crescent formation is unknown. In this study, we used confocal microscopy, laser capture microdissection, and real-time quantitative reverse transcriptase-PCR to demonstrate that hypercellular lesions of different podocytopathies and crescentic glomerulonephritis consist of three distinct populations: CD133(+)CD24(+)podocalyxin (PDX)(-)nestin(-) renal progenitors, CD133(+)CD24(+)PDX(+)nestin(+) transitional cells, and CD133(-)CD24(-)PDX(+)nestin(+) differentiated podocytes. In addition, TGF-beta induced CD133(+)CD24(+) progenitors to produce extracellular matrix, and these were the only cells to express the proliferation marker Ki67. Taken together, these results suggest that glomerular hyperplastic lesions derive from the proliferation of renal progenitors at different stages of their differentiation toward mature podocytes, providing an explanation for the pathogenesis of hyperplastic lesions in podocytopathies and crescentic glomerulonephritis.

Large cell non-Hodgkin's lymphoma masquerading as renal carcinoma with inferior vena cava thrombosis: a case report

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Weissman Alan

2011-06-01

Full Text Available Abstract Introduction Many cancers are associated with inferior vena cava (IVC obstruction, but very few cancers have the ability to propagate within the lumen of the renal vein or the IVC. Renal cell carcinoma is the most common of these cancers. Renal cancer with IVC extension has a high rate of recurrence and a low five year survival rate. Case presentation A 62-year-old Caucasian woman previously in good health developed the sudden onset of severe reflux symptoms and right-sided abdominal pain that radiated around the right flank. A subsequent ultrasound and CT scan revealed a right upper pole renal mass with invasion of the right adrenal gland, liver, left renal vein and IVC. This appeared to be consistent with stage III renal cancer with IVC extension. Metastatic nodules were believed to be present in the right pericardial region; the superficial anterior abdominal wall; the left perirenal, abdominal and pelvic regions; and the left adrenal gland. The pattern of these metastases, as well as the invasion of the liver by the tumor, was thought to be atypical of renal cancer. A needle biopsy of a superficial abdominal wall mass revealed a surprising finding: The malignant cells were diagnostic of large-cell, B-cell non-Hodgkin's lymphoma. The lymphoma responded dramatically to systemic chemotherapy, which avoided the need for nephrectomy. Conclusion Lymphomas only rarely progress via intraluminal vascular extension. We have been able to identify only one other case report of renal lymphoma with renal vein and IVC extension. While renal cancer would have been treated with radical nephrectomy and tumor embolectomy, large-cell B-cell lymphomas are treated primarily with chemotherapy, and nephrectomy would have been detrimental. It is important to remember that, rarely, other types of cancer arise from the kidney which are not derived from the renal tubular epithelium. These may be suspected if an atypical pattern of metastases or unusual

Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma

DEFF Research Database (Denmark)

Choueiri, Toni K; Escudier, Bernard; Powles, Thomas

2015-01-01

BACKGROUND: Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to an...

Urinary C-type natriuretic peptide excretion: a potential novel biomarker for renal fibrosis during aging.

Science.gov (United States)

Sangaralingham, S Jeson; Heublein, Denise M; Grande, Joseph P; Cataliotti, Alessandro; Rule, Andrew D; McKie, Paul M; Martin, Fernando L; Burnett, John C

2011-11-01

Renal aging is characterized by structural changes in the kidney including fibrosis, which contributes to the increased risk of kidney and cardiac failure in the elderly. Studies involving healthy kidney donors demonstrated subclinical age-related nephropathy on renal biopsy that was not detected by standard diagnostic tests. Thus there is a high-priority need for novel noninvasive biomarkers to detect the presence of preclinical age-associated renal structural and functional changes. C-type natriuretic peptide (CNP) possesses renoprotective properties and is present in the kidney; however, its modulation during aging remains undefined. We assessed circulating and urinary CNP in a Fischer rat model of experimental aging and also determined renal structural and functional adaptations to the aging process. Histological and electron microscopic analysis demonstrated significant renal fibrosis, glomerular basement membrane thickening, and mesangial matrix expansion with aging. While plasma CNP levels progressively declined with aging, urinary CNP excretion increased, along with the ratio of urinary to plasma CNP, which preceded significant elevations in proteinuria and blood pressure. Also, CNP immunoreactivity was increased in the distal and proximal tubules in both the aging rat and aging human kidneys. Our findings provide evidence that urinary CNP and its ratio to plasma CNP may represent a novel biomarker for early age-mediated renal structural alterations, particularly fibrosis. Thus urinary CNP could potentially aid in identifying subjects with preclinical structural changes before the onset of symptoms and disease, allowing for the initiation of strategies designed to prevent the progression of chronic kidney disease particularly in the aging population.

Unusual Upper Gastrointestinal Bleeding due to Late Metastasis from Renal Cell Carcinoma: A Case Report

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Wen-Tsan Chang

2004-03-01

Full Text Available A case of recurrent massive upper gastrointestinal bleeding originating from metastatic renal cell carcinoma is reported. A 63-year-old woman underwent right nephrectomy 9 years previously and experienced no recurrence during follow-up. A gradually enlarging ulcerative tumor over the bulb of the duodenum and four subsequent episodes of massive bleeding from this tumor occurred between June 2001 and March 2002. The patient underwent surgery in April 2002 for intractable bleeding from the tumor. Renal cell carcinoma metastasis to the duodenum was confirmed from the surgical specimen. Upper gastrointestinal bleeding due to malignancy is very rare and the duodenum is the least frequently involved site. Furthermore, a solitary late renal cell carcinoma metastasis 9 years after a nephrectomy is extremely uncommon. This case suggests that life-long follow-up of renal cell carcinoma patients is necessary, owing to unpredictable behavior and the possibility of long disease-free intervals. In nephrectomized patients suffering from gastrointestinal bleeding, complete evaluation, especially endoscopic examination, is indicated. The possibility of late recurrent renal cell carcinoma metastasis to the gastrointestinal tract should be kept in mind, although it is rare. If the patient is fit for surgery, metastatectomy is the first choice of treatment.

Hsa-let-7a functions as a tumor suppressor in renal cell carcinoma cell lines by targeting c-myc

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Liu, Yongchao; Yin, Bingde; Zhang, Changcun; Zhou, Libin [Department of Urology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080 (China); Fan, Jie, E-mail: jief67@sina.com [Department of Urology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080 (China)

2012-01-06

Highlights: Black-Right-Pointing-Pointer This study is the first to test the let-7a/c-myc loop in renal cell carcinoma cell lines. Black-Right-Pointing-Pointer Let-7a down-regulated c-myc in three renal cell carcinoma cell lines. Black-Right-Pointing-Pointer c-myc target genes were down-regulated because of the let-7a-mediated down-regulation of c-myc. Black-Right-Pointing-Pointer The let-7a/c-myc loop has a significant function in renal cell carcinoma cell lines. -- Abstract: Widespread functions of the c-myc pathway play a crucial role in renal cell carcinoma (RCC) carcinogenesis. Thus, we evaluated the connection between proto-oncogenic c-myc and anti-neoplastic hsa-let-7a (let-7a) in RCC cell lines. The levels of c-myc and let-7a in 3 RCC cell lines (769P, Caki-1 and 786O) were measured after transfecting the cells with let-7a mimics or a negative control. The change in c-myc protein level was confirmed by Western blot. The anti-neoplastic function of let-7a was evaluated using cell counting kit-8 (CCK-8) for proliferation analysis and cell flow cytometry for cell cycle analysis. The changes of downstream targets of c-myc were measured using reverse transcription quantitative real-time PCR (qRT-PCR). Our results suggest for the first time that let-7a acts as a tumor suppressor in RCC cell lines by down-regulating c-myc and c-myc target genes such as proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1) and the miR17-92 cluster, which is accompanied by proliferation inhibition and cell cycle arrest.

Improvement of renal function after human umbilical cord mesenchymal stem cell treatment on chronic renal failure and thoracic spinal cord entrapment: a case report.

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Rahyussalim, Ahmad Jabir; Saleh, Ifran; Kurniawati, Tri; Lutfi, Andi Praja Wira Yudha

2017-11-30

Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Thoracic spinal cord entrapment induced by a metabolic yield deposit in patients with renal failure results in intrusion of nervous tissue and consequently loss of motor and sensory function. Human umbilical cord mesenchymal stem cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Over the past decade, advances in the field of regenerative medicine allowed development of cell therapies suitable for kidney repair. Mesenchymal stem cell studies in animal models of chronic renal failure have uncovered a unique potential of these cells for improving function and regenerating the damaged kidney. We report a case of a 62-year-old ethnic Indonesian woman previously diagnosed as having thoracic spinal cord entrapment with paraplegic condition and chronic renal failure on hemodialysis. She had diabetes mellitus that affected her kidneys and had chronic renal failure for 2 years, with creatinine level of 11 mg/dl, and no urinating since then. She was treated with human umbilical cord mesenchymal stem cell implantation protocol. This protocol consists of implantation of 16 million human umbilical cord mesenchymal stem cells intrathecally and 16 million human umbilical cord mesenchymal stem cells intravenously. Three weeks after first intrathecal and intravenous implantation she could move her toes and her kidney improved. Her creatinine level decreased to 9 mg/dl. Now after 8 months she can raise her legs and her creatinine level is 2 mg/dl with normal urinating. Human umbilical cord mesenchymal stem cell implantations led to significant improvement for spinal cord entrapment and kidney failure. The major histocompatibility in allogeneic implantation is an important issue to be addressed in the future.

Yi Qi Qing Re Gao-containing serum inhibits lipopolysaccharide-induced rat mesangial cell proliferation by suppressing the Wnt pathway and TGF-β1 expression.

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Yang, Liping; Sun, Xueyan; Zhan, Yongli; Liu, Huijie; Wen, Yumin; Mao, Huimin; Dong, X I; Li, Ping

2016-04-01

The aim of the present study was to investigate the effect of Yi Qi Qing Re Gao-containing serum (YQ-S) on rat mesangial cell (MC) proliferation and to investigate the underlying mechanism. MCs were divided into the control, lipopolysaccharide (LPS)-stimulated, YQ-S and fosinopril-containing serum (For-S) groups, and cultured for 48 h. An MTT assay was used to evaluate the proliferation of MCs. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis were conducted to detect the expression levels of Wnt4, β-catenin and transforming growth factor (TGF)-β1 in MCs. The results indicated that YQ-S inhibited LPS-induced MC proliferation. The Wnt4 and TGF-β1 mRNA expression levels were reduced in the YQ-S group (P<0.01 or P<0.05). Furthermore, the Wnt4, β-catenin and TGF-β1 protein expression levels were suppressed in the YQ-S group (P<0.01 or P<0.05). Therefore, YQ-S appears to inhibit MC proliferation, and its mechanism may involve the inhibition of the Wnt signaling pathway and downregulation of TGF-β1 expression.

RENAL CRYOABLATION

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A. V. Govorov

2012-01-01

Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

Understanding familial and non-familial renal cell cancer

NARCIS (Netherlands)

Bodmer, Daniëlle; van den Hurk, Wilhelmina; van Groningen, Jan J. M.; Eleveld, Marc J.; Martens, Gerard J. M.; Weterman, Marian A. J.; van Kessel, Ad Geurts

2002-01-01

Molecular genetic analysis of familial and non-familial cases of conventional renal cell carcinoma (RCC) revealed a critical role(s) for multiple genes on human chromosome 3. For some of these genes, e.g. VHL, such a role has been firmly established, whereas for others, definite confirmation is

Understanding familial and non-familial renal cell cancer.

NARCIS (Netherlands)

Bodmer, D.; Hurk, W.H. van den; Groningen, J.J.M. van; Eleveld, M.J.; Martens, G.J.M.; Weterman, M.A.J.; Geurts van Kessel, A.H.M.

2002-01-01

Molecular genetic analysis of familial and non-familial cases of conventional renal cell carcinoma (RCC) revealed a critical role(s) for multiple genes on human chromosome 3. For some of these genes, e.g. VHL, such a role has been firmly established, whereas for others, definite confirmation is

Renal cell carcinoma: an atypical case containing fat

International Nuclear Information System (INIS)

Saez Castan, J.; Perez Paya, F.; Ramon Sanchez, J.; Rausell Felix, M.; Alpera Tenza, M.; Orti Tarazona, C.

1995-01-01

An atypical form of presentation of renal cell carcinoma is reported. The lesion contained fat collections, an exceptional findings in these neoplasms. We describe the intravenous urography, ultrasound and CT images, as well as the preoperative follow-up using CT, performed 11 months after the first study. 11 refs

The parietal epithelial cell is crucially involved in human idiopathic focal segmental glomerulosclerosis.

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Dijkman, Henry; Smeets, Bart; van der Laak, Jeroen; Steenbergen, Eric; Wetzels, Jack

2005-10-01

Focal segmental glomerulosclerosis (FSGS) is one of the most common patterns of glomerular injury encountered in human renal biopsies. Epithelial hyperplasia, which can be prominent in FSGS, has been attributed to dedifferentiation and proliferation of podocytes. Based on observations in a mouse model of FSGS, we pointed to the role of parietal epithelial cells (PECs). In the present study we investigated the relative role of PECs and podocytes in human idiopathic FSGS. We performed a detailed study of lesions from a patient with recurrent idiopathic FSGS by serial sectioning, marker analysis and three-dimensional reconstruction of glomeruli. We have studied the expression of markers for podocytes, PECs, mesangial cells, endothelium, and myofibroblasts. We also looked at proliferation and composition of the deposited extracellular matrix (ECM). We found that proliferating epithelial cells in FSGS lesions are negative for podocyte and macrophage markers, but stain for PEC markers. The composition of the matrix deposited by these cells is identical to Bowman's capsule. Our study demonstrates that PECs are crucially involved in the pathogenesis of FSGS lesions.

Differentiation of murine embryonic stem and induced pluripotent stem cells to renal lineage in vitro

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Morizane, Ryuji [Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan); Monkawa, Toshiaki, E-mail: monkawa@sc.itc.keio.ac.jp [Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan); Itoh, Hiroshi [Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan)

2009-12-25

Embryonic stem (ES) cells which have the unlimited proliferative capacity and extensive differentiation potency can be an attractive source for kidney regeneration therapies. Recent breakthroughs in the generation of induced pluripotent stem (iPS) cells have provided with another potential source for the artificially-generated kidney. The purpose of this study is to know how to differentiate mouse ES and iPS cells into renal lineage. We used iPS cells from mouse fibroblasts by transfection of four transcription factors, namely Oct4, Sox2, c-Myc and Klf4. Real-time PCR showed that renal lineage markers were expressed in both ES and iPS cells after the induction of differentiation. It also showed that a tubular specific marker, KSP progressively increased to day 18, although the differentiation of iPS cells was slower than ES cells. The results indicated that renal lineage cells can be differentiated from both murine ES and iPS cells. Several inducing factors were tested whether they influenced on cell differentiation. In ES cells, both of GDNF and BMP7 enhanced the differentiation to metanephric mesenchyme, and Activin enhanced the differentiation of ES cells to tubular cells. Activin also enhanced the differentiation of iPS cells to tubular cells, although the enhancement was lower than in ES cells. ES and iPS cells have a potential to differentiate to renal lineage cells, and they will be an attractive resource of kidney regeneration therapy. This differentiation is enhanced by Activin in both ES and iPS cells.

Renal cell carcinoma: histological classification and correlation with imaging findings

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Muglia, Valdair F., E-mail: fmuglia@fmrp.usp.br [Universidade de Sao Paulo (CCIFM/FMRP/USP), Ribeirao Preto, SP (Brazil). Centro de Ciencias das Imagens e Fisica Medica. Faculdade de Medicina; Prando, Adilson [Universidade Estadual de Campinas (UNICAMP), SP (Brazil); Hospital Vera Cruz, Campinas, SP (Brazil). Dept. de Imaginologia

2015-05-15

Renal cell carcinoma (RCC) is the seventh most common histological type of cancer in the Western world and has shown a sustained increase in its prevalence. The histological classification of RCCs is of utmost importance, considering the significant prognostic and therapeutic implications of its histological subtypes. Imaging methods play an outstanding role in the diagnosis, staging and follow-up of RCC. Clear cell, papillary and chromophobe are the most common histological subtypes of RCC, and their preoperative radiological characterization, either followed or not by confirmatory percutaneous biopsy, may be particularly useful in cases of poor surgical condition, metastatic disease, central mass in a solitary kidney, and in patients eligible for molecular targeted therapy. New strategies recently developed for treating renal cancer, such as cryo and radiofrequency ablation, molecularly targeted therapy and active surveillance also require appropriate preoperative characterization of renal masses. Less common histological types, although sharing nonspecific imaging features, may be suspected on the basis of clinical and epidemiological data. The present study is aimed at reviewing the main clinical and imaging findings of histological RCC subtypes. (author)

Ciglitazone induces caspase-independent apoptosis via p38-dependent AIF nuclear translocation in renal epithelial cells

International Nuclear Information System (INIS)

Kwon, Chae Hwa; Yoon, Chang Soo; Kim, Yong Keun

2008-01-01

Peroxisome proliferator-activated receptor γ (PPARγ) agonists have been reported to induce apoptosis in a variety of cell types including renal proximal epithelial cells. However, the underlying mechanism of cell death induced by PPARγ agonists has not been clearly defined in renal proximal tubular cells. This study was therefore undertaken to determine the mechanism by which ciglitazone, a synthetic PPARγ agonist, induces apoptosis in opossum kidney (OK) cells, an established renal epithelial cell line. Ciglitazone treatment induced apoptotic cell death in a dose- and time-dependent manner. Ciglitazone caused a transient activation of ERK and sustained activation of p38 MAP kinase. Ciglitazone-mediated cell death was attenuated by the p38 inhibitor SB203580 and transfection of dominant-negative form of p38, but not by the MEK inhibitor U0126, indicating that p38 MAP kinase activation is involved in the ciglitazone-induced cell death. Although ciglitazone-induced caspase-3 activation, the ciglitazone-mediated cell death was not affected by the caspase-3 inhibitor DEVD-CHO. Ciglitazone-induced mitochondrial membrane depolarization and apoptosis-inducing factor (AIF) nuclear translocation and these effects were prevented by the p38 inhibitor. These results suggest that ciglitazone induces caspase-independent apoptosis through p38 MAP kinase-dependent AIF nuclear translocation in OK renal epithelial cells

Renal cell carcinoma: evolving approaches to advanced non-clear cell carcinoma

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Daniel Y.C. Heng

2011-12-01

Full Text Available The treatment of metastatic renal cell carcinoma (RCC has changed dramatically with the introduction of targeted therapies including sunitinib, sorafenib, and temsirolimus. Because patients with conventional clear cell histology account for 75- 80% of all patients with RCC, there has been little accumulated evidence on the treatment of patients with non-clear cell histologies. Most clinical trials have excluded them from enrolment, except for randomized studies investigating temsirolimus. Many retrospective studies on the use of all three of these targeted therapies in patients with non-clear cell histology have demonstrated response rates ranging from 3.7%–16%. Although response rates may not be as high compared to patients with clear cell histologies, targeted therapy does provide a clinically meaningful response.

Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy.

Science.gov (United States)

Ravaud, Alain; Motzer, Robert J; Pandha, Hardev S; George, Daniel J; Pantuck, Allan J; Patel, Anup; Chang, Yen-Hwa; Escudier, Bernard; Donskov, Frede; Magheli, Ahmed; Carteni, Giacomo; Laguerre, Brigitte; Tomczak, Piotr; Breza, Jan; Gerletti, Paola; Lechuga, Mariajose; Lin, Xun; Martini, Jean-Francois; Ramaswamy, Krishnan; Casey, Michelle; Staehler, Michael; Patard, Jean-Jacques

2016-12-08

Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy. In this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety. The median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects. Among patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. (Funded by Pfizer; S-TRAC Clinical

Insulin-like growth factor-1 signaling in renal cell carcinoma

International Nuclear Information System (INIS)

Tracz, Adam F.; Szczylik, Cezary; Porta, Camillo; Czarnecka, Anna M.

2016-01-01

Renal cell carcinoma (RCC) incidence is highest in highly developed countries and it is the seventh most common neoplasm diagnosed. RCC management include nephrectomy and targeted therapies. Type 1 insulin-like growth factor (IGF-1) pathway plays an important role in cell proliferation and apoptosis resistance. IGF-1 and insulin share overlapping downstream signaling pathways in normal and cancer cells. IGF-1 receptor (IGF1R) stimulation may promote malignant transformation promoting cell proliferation, dedifferentiation and inhibiting apoptosis. Clear cell renal cell carcinoma (ccRCC) patients with IGF1R overexpression have 70 % increased risk of death compared to patients who had tumors without IGF1R expression. IGF1R signaling deregulation may results in p53, WT, BRCA1, VHL loss of function. RCC cells with high expression of IGF1R are more resistant to chemotherapy than cells with low expression. Silencing of IGF1R increase the chemosensitivity of ccRCC cells and the effect is greater in VHL mutated cells. Understanding the role of IGF-1 signaling pathway in RCC may result in development of new targeted therapeutic interventions. First preclinical attempts with anti-IGF-1R monoclonal antibodies or fragment antigen-binding (Fab) fragments alone or in combination with an mTOR inhibitor were shown to inhibit in vitro growth and reduced the number of colonies formed by of RCC cells

Comparative effects of mesenchymal stem cell therapy in distinct stages of chronic renal failure.

Science.gov (United States)

Caldas, Heloisa Cristina; de Paula Couto, Thaís Amarante Peres; Fernandes, Ida Maria Maximina; Baptista, Maria Alice Sperto Ferreira; Kawasaki-Oyama, Rosa Sayoko; Goloni-Bertollo, Eny Maria; Braile, Domingo Marcolino; Abbud-Filho, Mario

2015-10-01

The therapeutic potential of adult stem cells in the treatment of chronic diseases is becoming increasingly evident. In the present study, we sought to assess whether treatment with mesenchymal stem cells (MSCs) efficiently retards progression of chronic renal failure (CRF) when administered to experimental models of less severe CRF. We used two renal mass reduction models to simulate different stages of CRF (5/6 or 2/3 mass renal reduction). Renal functional parameters measured were serum creatinine (SCr), creatinine clearance (CCr), rate of decline in CCr (RCCr), and 24-h proteinuria (PT24h). We also evaluated renal morphology by histology and immunohistochemistry. MSCs were obtained from bone marrow aspirates and injected into the renal parenchyma of the remnant kidneys of both groups of rats with CRF (MSC5/6 or MSC2/3). Animals from groups MSC5/6 and CRF2/3 seemed to benefit from MSC therapy because they showed significantly reduction in SCr and PT24h, increase in CCr and slowed the RCCr after 90 days. Treatment reduced glomerulosclerosis but significant improvement did occur in the tubulointerstitial compartment with much less fibrosis and atrophy. MSC therapy reduced inflammation by decreasing macrophage accumulation proliferative activity (PCNA-positive cells) and fibrosis (α-SM-actin). Comparisons of renal functional and morphological parameters responses between the two groups showed that rats MSC2/3 were more responsive to MSC therapy than MSC5/6. This study showed that MSC therapy is efficient to retard CRF progression and might be more effective when administered during less severe stages of CRF.

Long-term Renal Function in Living Kidney Donors Who Had Histological Abnormalities at Donation.

Science.gov (United States)

Fahmy, Lara M; Massie, Allan B; Muzaale, Abimereki D; Bagnasco, Serena M; Orandi, Babak J; Alejo, Jennifer L; Boyarsky, Brian J; Anjum, Saad K; Montgomery, Robert A; Dagher, Nabil N; Segev, Dorry L

2016-06-01

Recent evidence suggests that living kidney donors are at an increased risk of end-stage renal disease. However, predicting which donors will have renal dysfunction remains challenging, particularly among those with no clinical evidence of disease at the time of donation. Although renal biopsies are not routinely performed as part of the donor evaluation process, they may yield valuable information that improves the ability to predict renal function in donors. We used implantation protocol biopsies to evaluate the association between histological abnormalities in the donated kidney and postdonation renal function (estimated glomerular filtration rate, eGFR) of the remaining kidney in living kidney donors. Longitudinal analysis using mixed-effects linear regression was used to account for multiple eGFR measures per donor. Among 310 donors between 1997 and 2012, median (IQR) follow-up was 6.2 (2.5-8.7; maximum 14.0) years. In this cohort, the overall prevalence of histological abnormalities was 65.8% (19.7% abnormal glomerulosclerosis, 23.9% abnormal interstitial fibrosis and tubular atrophy (IFTA), 4.8% abnormal mesangial matrix increase, 32.0% abnormal arteriolar hyalinosis, and 32.9% abnormal vascular intimal thickening). IFTA was associated with a 5-mL/min/1.73 m decrease of postdonation eGFR after adjusting for donor age at donation, sex, race, preoperative systolic blood pressure, preoperative eGFR, and time since donation (P < 0.01). In this single-center study, among healthy individuals cleared for living donation, IFTA was associated with decreased postdonation eGFR, whereas no other subclinical histological abnormalities provided additional information.

Lactate dehydrogenase as a biomarker for early renal damage in patients with sickle cell disease

Directory of Open Access Journals (Sweden)

Mohammad S Alzahri

2015-01-01

Full Text Available Among many complications of sickle cell disease, renal failure is the main contributor to early mortality. It is present in up to 21% of patients with sickle cell disease. Although screening for microalbuminuria and proteinuria is the current acceptable practice to detect and follow renal damage in patients with sickle cell disease, there is a crucial need for other, more sensitive biomarkers. This becomes especially true knowing that those biomarkers start to appear only after more than 60% of the kidney function is lost. The primary purpose of this study is to determine whether lactate dehydrogenase (LDH correlates with other, direct and indirect bio-markers of renal insufficiency in patients with sickle cell disease and, therefore, could be used as a biomarker for early renal damage in patients with sickle cell disease. Fifty-five patients with an established diagnosis of sickle cell disease were recruited to in the study. Blood samples were taken and 24-h urine collection samples were collected. Using Statcrunch, a data analysis tool available on the web, we studied the correlation between LDH and other biomarkers of kidney function as well as the distribution and relationship between the variables. Regression analysis showed a significant negative correlation between serum LDH and creatinine clearance, R (correlation coefficient = -0.44, P = 0.0008. This correlation was more significant at younger age. This study shows that in sickle cell patients LDH correlates with creatinine clearance and, therefore, LDH could serve as a biomarker to predict renal insufficiency in those patients.

Salubrious effect of C-phycocyanin against oxalate-mediated renal cell injury.

Science.gov (United States)

Farooq, Shukkur Muhammed; Asokan, Devarajan; Sakthivel, Ramasamy; Kalaiselvi, Periandavan; Varalakshmi, Palaninathan

2004-10-01

C-phycocyanin, a biliprotein pigment found in some blue green algae (Spirulina platensis) with nutritional and medicinal properties, was investigated for its efficacy on sodium oxalate-induced nephrotoxicity in experimentally induced urolithic rats. Male Wistar rats were divided into four groups. Hyperoxaluria was induced in two of these groups by intraperitoneal infusion of sodium oxalate (70 mg/kg), and a pretreatment of phycocyanin (100 mg/kg) as a single oral dosage was given to one of these groups by 1 h prior to sodium oxalate infusion challenges. The study also encompasses an untreated control group and a phycocyanin-alone treated drug control group. The extent of lipid peroxidation (LPO) was evaluated in terms of renal concentrations of MDA, conjugated diene and hydroperoxides. The following assay was performed in the renal tissue (a) antioxidant enzymes such as superoxide dismutase (SOD) and catalase, (b) glutathione metabolizing enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and glucose 6-phosphate dehydrogenase (G6PD), (c) the low molecular weight antioxidants (GSH, vitamins E and C) and protein carbonyl content. The increased concentrations of MDA, conjugated diene and hydroperoxide (index of the lipid peroxidation) were controlled (P antioxidants were appreciably increased (P antioxidants. It was noticed that the activities of antioxidant enzymes and glutathione metabolizing enzymes were considerably stabilized in rats pretreated with phycocyanin. We suggest that phycocyanin protects the integrity of the renal cell by stabilizing the free radical mediated LPO and protein carbonyl, as well as low molecular weight antioxidants and antioxidant enzymes in renal cells. Thus, the present analysis reveals that the antioxidant nature of C-phycocyanin protects the renal cell against oxalate-induced injury and may be a nephroprotective agent.

Renal cell carcinoma: new insights and challenges for a clinician scientist.

Science.gov (United States)

Shingarev, Roman; Jaimes, Edgar A

2017-08-01

There is a growing recognition of the complex interplay between renal cell cancer (RCC), kidney function, mechanical reduction of nephron mass, and systemic agents targeting the cancer. Earlier detection of RCC and rising life expectancy of cancer survivors places a greater emphasis on preservation of renal function after cancer resection and during systemic therapy. Unique adverse effects associated with RCC drugs not only help reveal cancer pathophysiology but also expand our knowledge of normal cell signaling and metabolism. In this review, we outline our current understanding of RCC biology and treatment, their bidirectional relationship with kidney function, and unmet research needs in this field. Copyright © 2017 the American Physiological Society.

Renal cell carcinoma: incidental detection and pathological staging.

Science.gov (United States)

Siow, W Y; Yip, S K; Ng, L G; Tan, P H; Cheng, W S; Foo, K T

2000-10-01

In developed countries, there has been increased incidental detection of renal cell carcinoma (RCC). The incidence, pathological stage and survival of incidentally detected carcinoma in a developing country in Asia where, from 1990 to 1998, 165 renal cell carcinomas were identified. The clinical presentation, diagnostic-imaging modality employed, pathological staging and patient survival was reviewed. Incidental renal cancers included those that were diagnosed through health screening or detected incidentally through imaging studies for other conditions. The survival between these incidentally detected lesions and their symptomatic counterparts (suspected group) was compared. Sixty-four patients (39%) had their tumours detected incidentally, including 39 who were entirely asymptomatic and 25 who presented with non-specific symptoms, not initially suggestive of RCC. For the entire group, computed tomography provided the definitive diagnosis in 81% of cases. The incidental detection group had significantly smaller size of tumour (5.9 cm c.f. 7.6 cm), lower stage and lower histological grading. In particular, 78% of patients with incidental RCC had stage I or II diseases (TNM stage classification), compared with 57% of patients with suspected tumour (p c.f. 66% at last follow up; p < 0.05; log-rank test) over a mean follow up period of 33 months (range 1-91). Regression analysis showed that stage of disease was the only independent variable predictive of clinical outcome. In conclusion, that significant numbers of RCC were detected incidentally. These tumours were of a lower clinical pathological stage and had a better prognosis.

Increased circulating follicular helper T cells with decreased programmed death-1 in chronic renal allograft rejection

OpenAIRE

Shi, Jian; Luo, Fengbao; Shi, Qianqian; Xu, Xianlin; He, Xiaozhou; Xia, Ying

2015-01-01

Background Chronic antibody-mediated rejection is a major issue that affects long-term renal allograft survival. Since follicular helper T (Tfh) cells promote the development of antigen-specific B cells in alloimmune responses, we investigated the potential roles of Tfh cells, B cells and their alloimmune-regulating molecules in the pathogenesis of chronic renal allograft rejection in this study. Methods The frequency of Tfh, B cells and the levels of their alloimmune-regulating molecules inc...

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

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Ricketts, Christopher J.; De Cubas, Aguirre A.; Fan, Huihui; Smith, Christof C.; Lang, Martin; Reznik, Ed; Bowlby, Reanne; Gibb, Ewan A.; Akbani, Rehan; Beroukhim, Rameen; Bottaro, Donald P.; Choueiri, Toni K.; Gibbs, Richard A.; Godwin, Andrew K.; Haake, Scott; Hakimi, A. Ari; Henske, Elizabeth P.; Hsieh, James J.; Ho, Thai H.; Kanchi, Rupa S.; Krishnan, Bhavani; Kwaitkowski, David J.; Lui, Wembin; Merino, Maria J.; Mills, Gordon B.; Myers, Jerome; Nickerson, Michael L.; Reuter, Victor E.; Schmidt, Laura S.; Shelley, Carl Simon; Shen, Hui; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Vincent, Benjamin G.; Vocke, Cathy D.; Wheeler, David A.; Yang, Lixing; Kim, William T.; Robertson, A. Gordon; Caesar-Johnson, Samantha J.; Demchok, John A.; Felau, Ina; Kasapi, Melpomeni; Ferguson, Martin L.; Hutter, Carolyn M.; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Cho, Juok; DeFreitas, Timothy; Frazer, Scott; Gehlenborg, Nils; Getz, Gad; Heiman, David I.; Kim, Jaegil; Lawrence, Michael S.; Lin, Pei; Meier, Sam; Noble, Michael S.; Saksena, Gordon; Voet, Doug; Zhang, Hailei; Bernard, Brady; Chambwe, Nyasha; Dhankani, Varsha; Knijnenburg, Theo; Kramer, Roger; Leinonen, Kalle; Liu, Yuexin; Miller, Michael; Reynolds, Sheila; Shmulevich, Ilya; Thorsson, Vesteinn; Zhang, Wei; Akbani, Rehan; Broom, Bradley M.; Hegde, Apurva M.; Ju, Zhenlin; Kanchi, Rupa S.; Korkut, Anil; Li, Jun; Liang, Han; Ling, Shiyun; Liu, Wenbin; Lu, Yiling; Mills, Gordon B.; Ng, Kwok Shing; Rao, Arvind; Ryan, Michael; Wang, Jing; Weinstein, John N.; Zhang, Jiexin; Abeshouse, Adam; Armenia, Joshua; Chakravarty, Debyani; Chatila, Walid K.; de Bruijn, Ino; Gao, Jianjiong; Gross, Benjamin E.; Heins, Zachary J.; Kundra, Ritika; La, Konnor; Ladanyi, Marc; Luna, Augustin; Nissan, Moriah G.; Ochoa, Angelica; Phillips, Sarah M.; Reznik, Ed; Sanchez-Vega, Francisco; Sander, Chris; Schultz, Nikolaus; Sheridan, Robert; Sumer, S. Onur; Sun, Yichao; Taylor, Barry S.; Wang, Jioajiao; Zhang, Hongxin; Anur, Pavana; Peto, Myron; Spellman, Paul; Benz, Christopher; Stuart, Joshua M.; Wong, Christopher K.; Yau, Christina; Hayes, D. Neil; Parker, Joel S.; Wilkerson, Matthew D.; Ally, Adrian; Balasundaram, Miruna; Bowlby, Reanne; Brooks, Denise; Carlsen, Rebecca; Chuah, Eric; Dhalla, Noreen; Holt, Robert; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen; Robertson, A. Gordon; Sadeghi, Sara; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Tse, Kane; Wong, Tina; Berger, Ashton C.; Beroukhim, Rameen; Cherniack, Andrew D.; Cibulskis, Carrie; Gabriel, Stacey B.; Gao, Galen F.; Ha, Gavin; Meyerson, Matthew; Schumacher, Steven E.; Shih, Juliann; Kucherlapati, Melanie H.; Kucherlapati, Raju S.; Baylin, Stephen; Cope, Leslie; Danilova, Ludmila; Bootwalla, Moiz S.; Lai, Phillip H.; Maglinte, Dennis T.; Van Den Berg, David J.; Weisenberger, Daniel J.; Auman, J. Todd; Balu, Saianand; Bodenheimer, Tom; Fan, Cheng; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Perou, Amy H.; Perou, Charles M.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Skelly, Tara; Soloway, Matthew G.; Tan, Donghui; Veluvolu, Umadevi; Fan, Huihui; Hinoue, Toshinori; Laird, Peter W.; Shen, Hui; Zhou, Wanding; Bellair, Michelle; Chang, Kyle; Covington, Kyle; Creighton, Chad J.; Dinh, Huyen; Doddapaneni, Harsha Vardhan; Donehower, Lawrence A.; Drummond, Jennifer; Gibbs, Richard A.; Glenn, Robert; Hale, Walker; Han, Yi; Hu, Jianhong; Korchina, Viktoriya; Lee, Sandra; Lewis, Lora; Li, Wei; Liu, Xiuping; Morgan, Margaret; Morton, Donna; Muzny, Donna; Santibanez, Jireh; Sheth, Margi; Shinbrot, Eve; Wang, Linghua; Wang, Min; Wheeler, David A.; Xi, Liu; Zhao, Fengmei; Hess, Julian; Appelbaum, Elizabeth L.; Bailey, Matthew; Cordes, Matthew G.; Ding, Li; Fronick, Catrina C.; Fulton, Lucinda A.; Fulton, Robert S.; Kandoth, Cyriac; Mardis, Elaine R.; McLellan, Michael D.; Miller, Christopher A.; Schmidt, Heather K.; Wilson, Richard K.; Crain, Daniel; Curley, Erin; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Candace; Shelton, Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik; Corcoran, Niall; Costello, Tony; Hovens, Christopher; Carvalho, Andre L.; de Carvalho, Ana C.; Fregnani, José H.; Longatto-Filho, Adhemar; Reis, Rui M.; Scapulatempo-Neto, Cristovam; Silveira, Henrique C.S.; Vidal, Daniel O.; Burnette, Andrew; Eschbacher, Jennifer; Hermes, Beth; Noss, Ardene; Singh, Rosy; Anderson, Matthew L.; Castro, Patricia D.; Ittmann, Michael; Huntsman, David; Kohl, Bernard; Le, Xuan; Thorp, Richard; Andry, Chris; Duffy, Elizabeth R.; Lyadov, Vladimir; Paklina, Oxana; Setdikova, Galiya; Shabunin, Alexey; Tavobilov, Mikhail; McPherson, Christopher; Warnick, Ronald; Berkowitz, Ross; Cramer, Daniel; Feltmate, Colleen; Horowitz, Neil; Kibel, Adam; Muto, Michael; Raut, Chandrajit P.; Malykh, Andrei; Barnholtz-Sloan, Jill S.; Barrett, Wendi; Devine, Karen; Fulop, Jordonna; Ostrom, Quinn T.; Shimmel, Kristen; Wolinsky, Yingli; Sloan, Andrew E.; De Rose, Agostino; Giuliante, Felice; Goodman, Marc; Karlan, Beth Y.; Hagedorn, Curt H.; Eckman, John; Harr, Jodi; Myers, Jerome; Tucker, Kelinda; Zach, Leigh Anne; Deyarmin, Brenda; Hu, Hai; Kvecher, Leonid; Larson, Caroline; Mural, Richard J.; Somiari, Stella; Vicha, Ales; Zelinka, Tomas; Bennett, Joseph; Iacocca, Mary; Rabeno, Brenda; Swanson, Patricia; Latour, Mathieu; Lacombe, Louis; Têtu, Bernard; Bergeron, Alain; McGraw, Mary; Staugaitis, Susan M.; Chabot, John; Hibshoosh, Hanina; Sepulveda, Antonia; Su, Tao; Wang, Timothy; Potapova, Olga; Voronina, Olga; Desjardins, Laurence; Mariani, Odette; Roman-Roman, Sergio; Sastre, Xavier; Stern, Marc Henri; Cheng, Feixiong; Signoretti, Sabina; Berchuck, Andrew; Bigner, Darell; Lipp, Eric; Marks, Jeffrey; McCall, Shannon; McLendon, Roger; Secord, Angeles; Sharp, Alexis; Behera, Madhusmita; Brat, Daniel J.; Chen, Amy; Delman, Keith; Force, Seth; Khuri, Fadlo; Magliocca, Kelly; Maithel, Shishir; Olson, Jeffrey J.; Owonikoko, Taofeek; Pickens, Alan; Ramalingam, Suresh; Shin, Dong M.; Sica, Gabriel; Van Meir, Erwin G.; Zhang, Hongzheng; Eijckenboom, Wil; Gillis, Ad; Korpershoek, Esther; Looijenga, Leendert; Oosterhuis, Wolter; Stoop, Hans; van Kessel, Kim E.; Zwarthoff, Ellen C.; Calatozzolo, Chiara; Cuppini, Lucia; Cuzzubbo, Stefania; DiMeco, Francesco; Finocchiaro, Gaetano; Mattei, Luca; Perin, Alessandro; Pollo, Bianca; Chen, Chu; Houck, John; Lohavanichbutr, Pawadee; Hartmann, Arndt; Stoehr, Christine; Stoehr, Robert; Taubert, Helge; Wach, Sven; Wullich, Bernd; Kycler, Witold; Murawa, Dawid; Wiznerowicz, Maciej; Chung, Ki; Edenfield, W. Jeffrey; Martin, Julie; Baudin, Eric; Bubley, Glenn; Bueno, Raphael; De Rienzo, Assunta; Richards, William G.; Kalkanis, Steven; Mikkelsen, Tom; Noushmehr, Houtan; Scarpace, Lisa; Girard, Nicolas; Aymerich, Marta; Campo, Elias; Giné, Eva; Guillermo, Armando López; Van Bang, Nguyen; Hanh, Phan Thi; Phu, Bui Duc; Tang, Yufang; Colman, Howard; Evason, Kimberley; Dottino, Peter R.; Martignetti, John A.; Gabra, Hani; Juhl, Hartmut; Akeredolu, Teniola; Stepa, Serghei; Hoon, Dave; Ahn, Keunsoo; Kang, Koo Jeong; Beuschlein, Felix; Breggia, Anne; Birrer, Michael; Bell, Debra; Borad, Mitesh; Bryce, Alan H.; Castle, Erik; Chandan, Vishal; Cheville, John; Copland, John A.; Farnell, Michael; Flotte, Thomas; Giama, Nasra; Ho, Thai; Kendrick, Michael; Kocher, Jean Pierre; Kopp, Karla; Moser, Catherine; Nagorney, David; O'Brien, Daniel; O'Neill, Brian Patrick; Patel, Tushar; Petersen, Gloria; Que, Florencia; Rivera, Michael; Roberts, Lewis; Smallridge, Robert; Smyrk, Thomas; Stanton, Melissa; Thompson, R. Houston; Torbenson, Michael; Yang, Ju Dong; Zhang, Lizhi; Brimo, Fadi; Ajani, Jaffer A.; Gonzalez, Ana Maria Angulo; Behrens, Carmen; Bondaruk, Jolanta; Broaddus, Russell; Czerniak, Bogdan; Esmaeli, Bita; Fujimoto, Junya; Gershenwald, Jeffrey; Guo, Charles; Lazar, Alexander J.; Logothetis, Christopher; Meric-Bernstam, Funda; Moran, Cesar; Ramondetta, Lois; Rice, David; Sood, Anil; Tamboli, Pheroze; Thompson, Timothy; Troncoso, Patricia; Tsao, Anne; Wistuba, Ignacio; Carter, Candace; Haydu, Lauren; Hersey, Peter; Jakrot, Valerie; Kakavand, Hojabr; Kefford, Richard; Lee, Kenneth; Long, Georgina; Mann, Graham; Quinn, Michael; Saw, Robyn; Scolyer, Richard; Shannon, Kerwin; Spillane, Andrew; Stretch, onathan; Synott, Maria; Thompson, John; Wilmott, James; Al-Ahmadie, Hikmat; Chan, Timothy A.; Ghossein, Ronald; Gopalan, Anuradha; Levine, Douglas A.; Reuter, Victor; Singer, Samuel; Singh, Bhuvanesh; Tien, Nguyen Viet; Broudy, Thomas; Mirsaidi, Cyrus; Nair, Praveen; Drwiega, Paul; Miller, Judy; Smith, Jennifer; Zaren, Howard; Park, Joong Won; Hung, Nguyen Phi; Kebebew, Electron; Linehan, W. Marston; Metwalli, Adam R.; Pacak, Karel; Pinto, Peter A.; Schiffman, Mark; Schmidt, Laura S.; Vocke, Cathy D.; Wentzensen, Nicolas; Worrell, Robert; Yang, Hannah; Moncrieff, Marc; Goparaju, Chandra; Melamed, Jonathan; Pass, Harvey; Botnariuc, Natalia; Caraman, Irina; Cernat, Mircea; Chemencedji, Inga; Clipca, Adrian; Doruc, Serghei; Gorincioi, Ghenadie; Mura, Sergiu; Pirtac, Maria; Stancul, Irina; Tcaciuc, Diana; Albert, Monique; Alexopoulou, Iakovina; Arnaout, Angel; Bartlett, John; Engel, Jay; Gilbert, Sebastien; Parfitt, Jeremy; Sekhon, Harman; Thomas, George; Rassl, Doris M.; Rintoul, Robert C.; Bifulco, Carlo; Tamakawa, Raina; Urba, Walter; Hayward, Nicholas; Timmers, Henri; Antenucci, Anna; Facciolo, Francesco; Grazi, Gianluca; Marino, Mirella; Merola, Roberta; de Krijger, Ronald; Gimenez-Roqueplo, Anne Paule; Piché, Alain; Chevalier, Simone; McKercher, Ginette; Birsoy, Kivanc; Barnett, Gene; Brewer, Cathy; Farver, Carol; Naska, Theresa; Pennell, Nathan A.; Raymond, Daniel; Schilero, Cathy; Smolenski, Kathy; Williams, Felicia; Morrison, Carl; Borgia, Jeffrey A.; Liptay, Michael J.; Pool, Mark; Seder, Christopher W.; Junker, Kerstin; Omberg, Larsson; Dinkin, Mikhail; Manikhas, George; Alvaro, Domenico; Bragazzi, Maria Consiglia; Cardinale, Vincenzo; Carpino, Guido; Gaudio, Eugenio; Chesla, David; Cottingham, Sandra; Dubina, Michael; Moiseenko, Fedor; Dhanasekaran, Renumathy; Becker, Karl Friedrich; Janssen, Klaus Peter; Slotta-Huspenina, Julia; Abdel-Rahman, Mohamed H.; Aziz, Dina; Bell, Sue; Cebulla, Colleen M.; Davis, Amy; Duell, Rebecca; Elder, J. Bradley; Hilty, Joe; Kumar, Bahavna; Lang, James; Lehman, Norman L.; Mandt, Randy; Nguyen, Phuong; Pilarski, Robert; Rai, Karan; Schoenfield, Lynn; Senecal, Kelly; Wakely, Paul; Hansen, Paul; Lechan, Ronald; Powers, James; Tischler, Arthur; Grizzle, William E.; Sexton, Katherine C.; Kastl, Alison; Henderson, Joel; Porten, Sima; Waldmann, Jens; Fassnacht, Martin; Asa, Sylvia L.; Schadendorf, Dirk; Couce, Marta; Graefen, Markus; Huland, Hartwig; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald; Tennstedt, Pierre; Olabode, Oluwole; Nelson, Mark; Bathe, Oliver; Carroll, Peter R.; Chan, June M.; Disaia, Philip; Glenn, Pat; Kelley, Robin K.; Landen, Charles N.; Phillips, Joanna; Prados, Michael; Simko, Jeffry; Smith-McCune, Karen; VandenBerg, Scott; Roggin, Kevin; Fehrenbach, Ashley; Kendler, Ady; Sifri, Suzanne; Steele, Ruth; Jimeno, Antonio; Carey, Francis; Forgie, Ian; Mannelli, Massimo; Carney, Michael; Hernandez, Brenda; Campos, Benito; Herold-Mende, Christel; Jungk, Christin; Unterberg, Andreas; von Deimling, Andreas; Bossler, Aaron; Galbraith, Joseph; Jacobus, Laura; Knudson, Michael; Knutson, Tina; Ma, Deqin; Milhem, Mohammed; Sigmund, Rita; Godwin, Andrew K.; Madan, Rashna; Rosenthal, Howard G.; Adebamowo, Clement; Adebamowo, Sally N.; Boussioutas, Alex; Beer, David; Giordano, Thomas; Mes-Masson, Anne Marie; Saad, Fred; Bocklage, Therese; Landrum, Lisa; Mannel, Robert; Moore, Kathleen; Moxley, Katherine; Postier, Russel; Walker, Joan; Zuna, Rosemary; Feldman, Michael; Valdivieso, Federico; Dhir, Rajiv; Luketich, James; Pinero, Edna M.Mora; Quintero-Aguilo, Mario; Carlotti, Carlos Gilberto; Dos Santos, Jose Sebastião; Kemp, Rafael; Sankarankuty, Ajith; Tirapelli, Daniela; Catto, James; Agnew, Kathy; Swisher, Elizabeth; Creaney, Jenette; Robinson, Bruce; Shelley, Carl Simon; Godwin, Eryn M.; Kendall, Sara; Shipman, Cassaundra; Bradford, Carol; Carey, Thomas; Haddad, Andrea; Moyer, Jeffey; Peterson, Lisa; Prince, Mark; Rozek, Laura; Wolf, Gregory; Bowman, Rayleen; Fong, Kwun M.; Yang, Ian; Korst, Robert; Rathmell, W. Kimryn; Fantacone-Campbell, J. Leigh; Hooke, Jeffrey A.; Kovatich, Albert J.; Shriver, Craig D.; DiPersio, John; Drake, Bettina; Govindan, Ramaswamy; Heath, Sharon; Ley, Timothy; Van Tine, Brian; Westervelt, Peter; Rubin, Mark A.; Lee, Jung Il; Aredes, Natália D.; Mariamidze, Armaz; Spellman, Paul T.; Rathmell, W. Kimryn; Linehan, W. Marston

2018-01-01

Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC,

Alveolar architecture of clear cell renal carcinomas (≤5.0 cm) show high attenuation on dynamic CT scanning

International Nuclear Information System (INIS)

Fujimoto, Hiroyuki; Wakao, Fumihiko; Moriyama, Noriyuki; Tobisu, Kenichi; Kakizoe, Tadao; Sakamoto, Michiie

1999-01-01

To establish the correlation between tumor appearance on CT and tumor histology in renal cell carcinomas. The density and attenuation patterns of 96 renal cell carcinomas, each ≤5 cm in greatest diameter, were studied by non-enhanced CT and early and late after bolus injection of contrast medium using dynamic CT. The density and attenuation patterns and pathological maps of each tumor were individually correlated. High attenuated areas were present in 72 of the 96 tumors on early enhanced dynamic CT scanning. All 72 high attenuated areas were of the clear cell renal cell carcinoma and had alveolar architecture. The remaining 24 tumors that did not demonstrate high attenuated foci on early enhanced scanning included three clear cell, nine granular cell, six papillary, five chromophobe and one collecting duct type. With respect to tumor architecture, all clear cell tumors of alveolar architecture demonstrated high attenuation on early enhanced scanning. Clear cell renal cell carcinomas of alveolar architecture show high attenuation on early enhanced dynamic CT scanning. A larger number of patients are indispensable to obtaining clear results. However, these findings seem to be an important clue to the diagnosis of renal cell carcinomas as having an alveolar structure. (author)

Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma: a clinical phase 1/2 trial

DEFF Research Database (Denmark)

Berntsen, Annika; Trepiakas, Redas; Wenandy, Lynn

2008-01-01

Therapeutic dendritic cell (DC) vaccination against cancer is a strategy aimed at activating the immune system to recognize and destroy tumor cells. In this nonrandomized phase 1/2 trial, we investigated the safety, feasibility, induction of T-cell response, and clinical response after treatment...... with a DC-based vaccine in patients with metastatic renal cell carcinoma. Twenty-seven patients with progressive cytokine-refractory metastatic renal cell carcinoma were vaccinated with DCs loaded with either a cocktail of survivin and telomerase peptides or tumor lysate depending on their HLA-A2 haplotype......, and low-dose IL-2 was administered concomitantly. Tumor response, immune response, and serum IL-6 and YKL-40 were measured during treatment. Vaccine generation was successful in all patients and no serious adverse events were observed. None of the patients had an objective response but 13/27 patients...

Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC Pathways

Directory of Open Access Journals (Sweden)

Aiqing Zhang

2015-06-01

Full Text Available Aims: This study aimed to explore the precise mechanism and signaling pathways of mesangial cell (MC proliferation from a new point of view considering Connexin 43 (Cx43. Methods: MC proliferation was measured by the incorporation of 3H-thymidine (3H-TdR. Cx43 was over-expressed in MC cells using lipofectamine 2000, and the expression level was tested with reverse transcription-polymerase chain reaction (RT-PCR and Western blot analyses. The gap junction channel function was explored by Lucifer Yellow scrape loading and dye transfer (SLDT, and the intracellular calcium concentrations ([Ca2+]i were characterized by confocal microscopy on cells loaded with Fura-3/AM. Results: There was an inverse correlation between Cx43 expression and MC proliferation (P0.05. Our data also showed that the mineralcorticoid receptor (MR antagonist spironolactone, ERK1/2 inhibitor PD98059 and PKC inhibitor GF109203X could attenuate the down-regulation of Cx43 expression in Aldo-induced MC proliferation; however, the PI3K inhibitor LY294002 could block MC proliferation without affecting Cx43 expression at either the mRNA or protein level. In addition, Aldo promoted MC proliferation in parallel with increasing [Ca2+]i (PConclusions: Our study provides preliminary evidence that Cx43 is an important regulator of Aldo-promoted MC proliferation. Furthermore, reduced Cx43 expression promoted MC proliferation independent of the gap junction channel function, and this process might be mediated through the ERK1/2- and PKC-dependent pathways.

Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

Directory of Open Access Journals (Sweden)

Ding F

2014-09-01

Full Text Available Fengan Ding,1 Yiping Li,1 Jing Liu,1 Lei Liu,1 Wenmin Yu,1 Zhi Wang,1 Haifeng Ni,2 Bicheng Liu,2 Pingsheng Chen1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Institute of Nephrology, The Affiliated Zhongda Hospital, Southeast University, Nanjing, People’s Republic of China Background: Gold nanoparticles (GNPs can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells.Results: Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM to human renal proximal tubular cells (HK-2 by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the

Does injection of metanephric mesenchymal cells improve renal function in rats?

Directory of Open Access Journals (Sweden)

Yu-qing Jiao

2011-01-01

Full Text Available Chronic kidney disease (CKD is a massive global health-care problem. Cell therapy offers a potential treatment for CKD. The aim of this study was to investigate whether the administration of a population of stem cells could be used to treat adriamycin (ADR-induced glomerulopathy in rats, a form of CKD. We intravenously transplanted metanephric mesenchymal cells (MMCs into rats treated with ADR. We also induced MMC differentiation in vitro using a medium derived from serum and homogenates of ADR-induced glomerulopathy rats. We detected the induction of an early epithelial phenotype (cytokeratin-18 expression and a proximal tubule phenotype (vitamin D receptor expression in vitro, and MMC-derived epithelial cells corresponding to the proximal tubule and glomeruli in vivo. Transplantation of MMCs after induction of glomerulopathy significantly increased the creatinine clearance rate (Ccr, a marker for glomerular filtration rate, but had no significant effect on other parameters (24-hour urinary protein excretion, serum albumin, total cholesterol. In addition, there was no significant difference in blood urea nitrogen or serum creatinine levels in rats with and without ADR administration. Our results indicate that MMCs might survive, engraft and differentiate into renal epithelia in vivo when transplanted into ADR-treated rats. However, further studies are needed to determine whether MMC transplantation improves renal function and causes renal repair in this model.

Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

DEFF Research Database (Denmark)

Andersen, Rikke; Donia, Marco; Westergaard, Marie Christine Wulff

2015-01-01

stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe...

Metastasis Targeted Therapies in Renal Cell Cancer

OpenAIRE

K. Fehmi Narter; Bora Özveren

2018-01-01

Metastatic renal cell cancer is a malignant disease and its treatment has been not been described clearly yet. These patients are generally symptomatic and resistant to current treatment modalities. Radiotherapy, chemotherapy, and hormonal therapy are not curative in many of these patients. A multimodal approach consisting of cytoreductive nephrectomy, systemic therapy (immunotherapy or targeted molecules), and metastasectomy has been shown to be hopeful in prolonging the survival and improvi...

Sequestration of human cytomegalovirus by human renal and mammary epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Twite, Nicolas [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Andrei, Graciela [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Kummert, Caroline [ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Donner, Catherine [Department of Obstetrics and Gynecology, Erasme Hospital, Route de Lennik 808, 1070 Brussels (Belgium); Perez-Morga, David [Laboratory of Molecular Parasitology, Institut de Biologie et Médecine Moléculaires, Université Libre de Bruxelles, Gosselies (Belgium); De Vos, Rita [Pathology Department, U.Z. Leuven, Minderbroedersstraat 12, Leuven (Belgium); Snoeck, Robert, E-mail: Robert.Snoeck@Rega.kuleuven.be [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Marchant, Arnaud, E-mail: arnaud.marchant@ulb.ac.be [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium)

2014-07-15

Urine and breast milk represent the main routes of human cytomegalovirus (HCMV) transmission but the contribution of renal and mammary epithelial cells to viral excretion remains unclear. We observed that kidney and mammary epithelial cells were permissive to HCMV infection and expressed immediate early, early and late antigens within 72 h of infection. During the first 24 h after infection, high titers of infectious virus were measured associated to the cells and in culture supernatants, independently of de novo synthesis of virus progeny. This phenomenon was not observed in HCMV-infected fibroblasts and suggested the sequestration and the release of HCMV by epithelial cells. This hypothesis was supported by confocal and electron microscopy analyses. The sequestration and progressive release of HCMV by kidney and mammary epithelial cells may play an important role in the excretion of the virus in urine and breast milk and may thereby contribute to HCMV transmission. - Highlights: • Primary renal and mammary epithelial cells are permissive to HCMV infection. • HCMV is sequestered by epithelial cells and this phenomenon does not require viral replication. • HCMV sequestration by epithelial cells is reduced by antibodies and IFN-γ.

The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

NARCIS (Netherlands)

Davis, Caleb F; Ricketts, Christopher J; Wang, Min; Yang, Lixing; Cherniack, Andrew D; Shen, Hui; Buhay, Christian; Kang, Hyojin; Kim, Sang Cheol; Fahey, Catherine C; Hacker, Kathryn E; Bhanot, Gyan; Gordenin, Dmitry A; Chu, Andy; Gunaratne, Preethi H; Biehl, Michael; Seth, Sahil; Kaipparettu, Benny A; Bristow, Christopher A; Donehower, Lawrence A; Wallen, Eric M; Smith, Angela B; Tickoo, Satish K; Tamboli, Pheroze; Reuter, Victor; Schmidt, Laura S; Hsieh, James J; Choueiri, Toni K; Hakimi, A Ari; Chin, Lynda; Meyerson, Matthew; Kucherlapati, Raju; Park, Woong-Yang; Robertson, A Gordon; Laird, Peter W; Henske, Elizabeth P; Kwiatkowski, David J; Park, Peter J; Morgan, Margaret; Shuch, Brian; Muzny, Donna; Wheeler, David A; Linehan, W Marston; Gibbs, Richard A; Rathmell, W Kimryn; Creighton, Chad J

2014-01-01

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared

Cell kinetics of differentiation of Na+-dependent hexose transport in a cultured renal epithelial cell line

International Nuclear Information System (INIS)

Cook, J.S.; Weiss, E.R.

1985-01-01

Fully differentiated cells of the renal proximal tubule have the capability of taking up hexoses across their apical borders by transport coupled to the Na + -electrochemical gradient. This property is also found in postconfluent cultures of the cloned cell line LLC-PK 1 , a morphologically polarized line of renal cells. Postconfluent cells develop the Na + -dependent capacity to transport hexoses at their apical surface. This function is not observable during the growth phase of the cultures. To analyze the developmental process at the cellular level a method has been derived to separate transporting cells, expressing the differentiated function, from nontransporting cells. The method is based on the swelling of the cells accompanying the uptake of the nonmetabolizable glucose analog alpha methylglucoside. The swollen cells have a lower buoyant density than the undifferentiated cells and may be separated from them on density gradients. Analysis of the distribution of cells on such gradients shows that after the cells reach confluence the undifferentiated subpopulation is recruited onto the differentiation pathway with a rate constant of 0.2 per day, that 5 to 7 days are required for a cell to traverse this pathway to the fully differentiated state, and that once the maximum uptake capacity is achieved the cells do not develop further

Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma.

Science.gov (United States)

Ambrosio, Maria R; Rocca, Bruno J; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T; Tripodi, Sergio A; Tosi, Piero

2015-01-01

Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis.

A case of renal cell carcinoma and angiomyolipoma in an ...

African Journals Online (AJOL)

Abstract. We describe a case of renal cell carcinoma in the right kidney together with an angiomyolipoma in the left kidney, encountered in an adolescent girl at Potchefstroom Provincial Hospital, North West Province, South Africa.

Intensity ratio curve analysis of small renal masses on T2-weighted magnetic resonance imaging: Differentiation of fat-poor angiomyolipoma from renal cell carcinoma.

Science.gov (United States)

Moriyama, Shingo; Yoshida, Soichiro; Tanaka, Hajime; Tanaka, Hiroshi; Yokoyama, Minato; Ishioka, Junichiro; Matsuoka, Yoh; Saito, Kazutaka; Kihara, Kazunori; Fujii, Yasuhisa

2018-03-25

To assess the diagnostic ability of a pixel intensity-based analysis in evaluating the magnetic resonance imaging characteristics of small renal masses, especially in differentiating fat-poor angiomyolipoma from renal cell carcinoma. T2-weighted images from 121 solid small renal masses (ratio curve was plotted using intensity ratios, which were ratios of signal intensities of tumor pixels (each pixel along a linear region of interest drawn across the renal tumor on T2-weighted image) to the signal intensity of a normal renal cortex. The diagnostic ability of the intensity ratio curve analysis was evaluated. The tumors were classified into three types: intensity ratio fat-poor angiomyolipoma (n = 19) with no pseudocapsule, iso-low intensity and no heterogeneity; intensity ratio clear cell renal cell carcinoma (n = 76) with a pseudocapsule, iso-high intensity and heterogeneity; and other type of intensity ratio (n = 26), including tumors that did not fall into the above two categories. The sensitivity/specificity/accuracy of the intensity ratio curve analysis in diagnosing fat-poor angiomyolipoma was 93%/94%/94%, respectively. When the intensity ratio curve analysis was applied only to the tumor with undetermined radiological diagnosis, the sensitivity for diagnosing fat-poor angiomyolipoma compared with subjective reading alone significantly improved (93% vs 50%; P = 0.014). Our novel semiquantitative model for combined assessment of key features of fat-poor angiomyolipoma, including low intensity, homogeneity and absence of a pseudocapsule on T2-weighted image, might make diagnosis of fat-poor angiomyolipoma more accurate. © 2018 The Japanese Urological Association.

Xenobiotic Metabolizing Gene Variants and Renal Cell Cancer: A Multicenter Study

International Nuclear Information System (INIS)

Heck, Julia E.; Moore, Lee E.; Lee, Yuan-Chin A.; McKay, James D.; Hung, Rayjean J.; Karami, Sara; Gaborieau, Valérie; Szeszenia-Dabrowska, Neonila; Zaridze, David G.; Mukeriya, Anush; Mates, Dana; Foretova, Lenka; Janout, Vladimir; Kollárová, Helena; Bencko, Vladimir; Rothman, Nathaniel; Brennan, Paul; Chow, Wong-Ho; Boffetta, Paolo

2012-01-01

Background: The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer (RCC). Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. Methods: The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case–control study conducted between 1998 and 2003 across seven centers in Central and Eastern Europe. Detailed data were collected from 874 cases and 2053 controls on demographics, work history, and occupational exposure to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase (UGT)] were selected for the present analysis based on their putative role in xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for country of residence, age, sex, smoking, alcohol intake, obesity, and hypertension. Results: We observed an increased risk of RCC with one SNP. After adjustment for multiple comparisons it did not remain significant. Neither NAT1 nor NAT2 slow acetylation was associated with disease. Conclusion: We observed no association between this pathway and renal cell cancer.

Xenobiotic Metabolizing Gene Variants and Renal Cell Cancer: A Multicenter Study

Energy Technology Data Exchange (ETDEWEB)

Heck, Julia E. [International Agency for Research on Cancer, Lyon (France); Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, CA (United States); Moore, Lee E. [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Lee, Yuan-Chin A. [International Agency for Research on Cancer, Lyon (France); Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, CA (United States); McKay, James D. [International Agency for Research on Cancer, Lyon (France); Hung, Rayjean J. [Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, ON (Canada); Karami, Sara [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Gaborieau, Valérie [International Agency for Research on Cancer, Lyon (France); Szeszenia-Dabrowska, Neonila [Department of Epidemiology, Institute of Occupational Medicine, Lodz (Poland); Zaridze, David G. [Cancer Research Centre, Institute of Carcinogenesis, Moscow (Russian Federation); Mukeriya, Anush [Cancer Research Centre, Department of Epidemiology, Moscow (Russian Federation); Mates, Dana [Institute of Public Health, Bucharest (Romania); Foretova, Lenka [Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno (Czech Republic); Janout, Vladimir; Kollárová, Helena [Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc (Czech Republic); Bencko, Vladimir [First Faculty of Medicine, Institute of Hygiene and Epidemiology, Charles University in Prague, Prague, Czech Republic (Czech Republic); Rothman, Nathaniel [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Brennan, Paul [International Agency for Research on Cancer, Lyon (France); Chow, Wong-Ho [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Boffetta, Paolo, E-mail: paolo.boffetta@mssm.edu [International Prevention Research Institute, Lyon (France); Tisch Cancer Institute, Mt. Sinai School of Medicine, New York, NY (United States)

2012-02-20

Background: The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer (RCC). Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. Methods: The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case–control study conducted between 1998 and 2003 across seven centers in Central and Eastern Europe. Detailed data were collected from 874 cases and 2053 controls on demographics, work history, and occupational exposure to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase (UGT)] were selected for the present analysis based on their putative role in xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for country of residence, age, sex, smoking, alcohol intake, obesity, and hypertension. Results: We observed an increased risk of RCC with one SNP. After adjustment for multiple comparisons it did not remain significant. Neither NAT1 nor NAT2 slow acetylation was associated with disease. Conclusion: We observed no association between this pathway and renal cell cancer.

Renal progenitor cells contribute to hyperplastic lesions of podocytopathies and crescentic glomerulonephritis.

NARCIS (Netherlands)

Smeets, B.; Angelotti, M.L.; Rizzo, P.; Dijkman, H.; Lazzeri, E.; Mooren, F.; Ballerini, L.; Parente, E.; Sagrinati, C.; Mazzinghi, B.; Ronconi, E.; Becherucci, F.; Benigni, A.; Steenbergen, E.; Lasagni, L.; Remuzzi, G.; Wetzels, J.F.M.; Romagnani, P.

2009-01-01

Glomerular injury can involve excessive proliferation of glomerular epithelial cells, resulting in crescent formation and obliteration of Bowman's space. The origin of these hyperplastic epithelial cells in different glomerular disorders is controversial. Renal progenitors localized to the inner

Loss of the BMP antagonist USAG-1 ameliorates disease in a mouse model of the progressive hereditary kidney disease Alport syndrome.

Science.gov (United States)

Tanaka, Mari; Asada, Misako; Higashi, Atsuko Y; Nakamura, Jin; Oguchi, Akiko; Tomita, Mayumi; Yamada, Sachiko; Asada, Nariaki; Takase, Masayuki; Okuda, Tomohiko; Kawachi, Hiroshi; Economides, Aris N; Robertson, Elizabeth; Takahashi, Satoru; Sakurai, Takeshi; Goldschmeding, Roel; Muso, Eri; Fukatsu, Atsushi; Kita, Toru; Yanagita, Motoko

2010-03-01

The glomerular basement membrane (GBM) is a key component of the filtering unit in the kidney. Mutations involving any of the collagen IV genes (COL4A3, COL4A4, and COL4A5) affect GBM assembly and cause Alport syndrome, a progressive hereditary kidney disease with no definitive therapy. Previously, we have demonstrated that the bone morphogenetic protein (BMP) antagonist uterine sensitization-associated gene-1 (USAG-1) negatively regulates the renoprotective action of BMP-7 in a mouse model of tubular injury during acute renal failure. Here, we investigated the role of USAG-1 in renal function in Col4a3-/- mice, which model Alport syndrome. Ablation of Usag1 in Col4a3-/- mice led to substantial attenuation of disease progression, normalization of GBM ultrastructure, preservation of renal function, and extension of life span. Immunohistochemical analysis revealed that USAG-1 and BMP-7 colocalized in the macula densa in the distal tubules, lying in direct contact with glomerular mesangial cells. Furthermore, in cultured mesangial cells, BMP-7 attenuated and USAG-1 enhanced the expression of MMP-12, a protease that may contribute to GBM degradation. These data suggest that the pathogenetic role of USAG-1 in Col4a3-/- mice might involve crosstalk between kidney tubules and the glomerulus and that inhibition of USAG-1 may be a promising therapeutic approach for the treatment of Alport syndrome.

βENaC acts as a mechanosensor in renal vascular smooth muscle cells that contributes to renal myogenic blood flow regulation, protection from renal injury and hypertension.

Science.gov (United States)

Drummond, Heather A; Stec, David E

2015-06-01

Pressure-induced constriction (also known as the "myogenic response") is an important mechanodependent response in small renal arteries and arterioles. The response is initiated by vascular smooth muscle cell (VSMC) stretch due to an increase in intraluminal pressure and leads to vasoconstriction. The myogenic response has two important roles as a mechanism of local blood flow autoregulation and protection against systemic blood pressure-induced microvascular damage. However, the molecular mechanisms underlying initiation of myogenic response are unresolved. Although several molecules have been considered initiators of the response, our laboratory has focused on the role of degenerin proteins because of their strong evolutionary link to mechanosensing in the nematode. Our laboratory has addressed the hypothesis that certain degenerin proteins act as mechanosensors in VSMCs. This article discusses the importance of a specific degenerin protein, β Epithelial Na + Channel (βENaC), in pressure-induced vasoconstriction, renal blood flow and susceptibility to renal injury. We propose that loss of the renal myogenic constrictor response delays the correction of renal blood flow that occurs with fluctuations in systemic pressure, which allows pressure swings to be transmitted to the microvasculature, thus increasing the susceptibility to renal injury and hypertension. The role of βENaC in myogenic regulation is independent of tubular βENaC and thus represents a non-tubular role for βENaC in renal-cardiovascular homeostasis.

Severe hypertriglyceridemia and hypercholesterolemia accelerating renal injury: a novel model of type 1 diabetic hamsters induced by short-term high-fat / high-cholesterol diet and low-dose streptozotocin.

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He, Liang; Hao, Lili; Fu, Xin; Huang, Mingshu; Li, Rui

2015-04-11

Hyperlipidemia is thought to be a major risk factor for the progression of renal diseases in diabetes. Recent studies have shown that lipid profiles are commonly abnormal early on type 2 diabetes mellitus (T2DM) with diabetic nephropathy. However, the early effects of triglyceride and cholesterol abnormalities on renal injury in type 1 diabetes mellitus (T1DM) are not fully understood and require reliable animal models for exploration of the underlying mechanisms. Hamster models are important tools for studying lipid metabolism because of their similarity to humans in terms of lipid utilization and high susceptibility to dietary cholesterol and fat. Twenty-four male Golden Syrian hamsters (100-110 g) were rendered diabetes by intraperitoneal injections of streptozotocin (STZ) on consecutive 3 days at dose of 30 mg/kg, Ten days after STZ injections, hamsters with a plasma Glu concentration more than 12 mmol/L were selected as insulin deficient ones and divided into four groups (D-C, D-HF, D-HC, and D-HFHC), and fed with commercially available standard rodent chow, high-fat diet, high-cholesterol diet, high-fat and cholesterol diet respectively, for a period of four weeks. After an induction phase, a stable model of renal injury was established with the aspects of early T1DM kidney disease, These aspects were severe hypertriglyceridemia, hypercholesterolemia, proteinuria with mesangial matrix accumulation, upgraded creatinine clearance, significant cholesterol and triglyceride deposition, and increasing glomerular surface area, thickness of basement membrane and mesangial expansion. The mRNA levels of sterol regulatory element binding protein-1c, transforming growth factors-β, plasminogen activator inhibitor-1, tumor necrosis factor-α and interleukin-6 in the D-HFHC group were significantly up-regulated compared with control groups. This study presents a novel, non-transgenic, non-surgical method for induction of renal injury in hamsters, which is an important

Clinical Relevance of Gene Copy Number Variation in Metastatic Clear Cell Renal Cell Carcinoma.

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Nouhaud, François-Xavier; Blanchard, France; Sesboue, Richard; Flaman, Jean-Michel; Sabourin, Jean-Christophe; Pfister, Christian; Di Fiore, Frédéric

2018-02-23

Gene copy number variations (CNVs) have been reported to be frequent in renal cell carcinoma (RCC), with potential prognostic value for some. However, their clinical utility, especially to guide treatment of metastatic disease remains to be established. Our objectives were to assess CNVs on a panel of selected genes and determine their clinical relevance in patients who underwent treatment of metastatic RCC. The genetic assessment was performed on frozen tissue samples of clear cell metastatic RCC using quantitative multiplex polymerase chain reaction of short fluorescent fragment method to detect CNVs on a panel of 14 genes of interest. The comparison of the electropherogram obtained from both tumor and normal renal adjacent tissue allowed for CNV identification. The clinical, biologic, and survival characteristics were assessed for their associations with the most frequent CNVs. Fifty patients with clear cell metastatic RCC were included. The CNV rate was 21.4%. The loss of CDKN2A and PLG was associated with a higher tumor stage (P relevance, especially those located on CDKN2A, PLG, and ALDOB, in a homogeneous cohort of patients with clear cell metastatic RCC. Copyright © 2018 Elsevier Inc. All rights reserved.

Leiomyosarcoma of the renal pelvis

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Dhamne Sagar

2009-10-01

Full Text Available Leiomyosarcomas are rare malignant tumors of the kidney. They may arise from the renal capsule, renal vein, renal pelvic musculature or renal parenchyma. Renal pelvis is an uncommon site of occurrence, with around 10 cases reported in the literature so far. Here we present a 60-year-old male who presented with increased urinary frequency, lower limb weakness, anorexia and weight loss. Imaging showed a right renal mass. A renal cell carcinoma was suspected clinically. A right nephrectomy was performed, which showed a large circumscribed mass in the hilar region. Histology revealed a tumor mass arising from the renal pelvis. The tumor was composed of spindle cells arranged in fascicles. Immunohistochemistry showed tumor cells to be positive for smooth muscle actin (SMA and desmin (Des and negative for cytokeratin (CK, HMB 45, CD117 (C-kit, and CD34. That confirmed the diagnosis of leiomyosarcoma.

Hordenine protects against hyperglycemia-associated renal complications in streptozotocin-induced diabetic mice.

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Su, Shuhao; Cao, Meng; Wu, Guangyuan; Long, Zi; Cheng, Xiaodong; Fan, Junshu; Xu, Zhongrui; Su, Hongfei; Hao, Yiming; Li, Ge; Peng, Jie; Li, Shuang; Wang, Xin

2018-05-15

The worldwide prevalence of diabetes and associated metabolic diseases has dramatically increased. Pharmacological treatment of diabetes is still limited. Hordenine (HOR), a phenethylamine alkaloid, is a natural constituent in many plants. The present study was designed to explore the possible anti-diabetic effect of HOR in streptozotocin (STZ)-induced diabetic mice. Combined treatment of HOR and insulin significantly reduced fasting and postprandial blood glucose level in diabetic mice. HOR and insulin did not show evident protective effect against structural and functional injuries of pancreas. Renal histological and functional injuries were significantly improved by HOR or insulin treatment. Moreover, combined treatment of HOR and insulin resulted in a more significant amelioration of renal histological and functional injuries in diabetic mice. HOR induced a decrease of renal IL-1α/β and IL-6 expression, and a reduction of Col1α1 and MMP9 expression and PAS-stained mesangial expansion in glomeruli of diabetic mice. In diabetic mice, HOR significantly decreased Nrf2 expression and increased hnRNPF and hnRNPK expression in kidney. Moreover, HOR showed a synergistic effect with insulin on the expression of these regulators. Renal ROS level and TBARS content in diabetic mice were decreased by HOR. The reduction of renal expression of antioxidant enzymes in diabetic mice was inhibited by HOR and insulin. Furthermore, HOR and insulin function synergistically to play an antioxidant role against oxidative injury in diabetic nephropathy. In conclusion, to the best of our knowledge, we, for the first time, found the anti-diabetic, anti-inflammatory, and anti-fibrotic role of HOR in combination with insulin. HOR functions synergistically with insulin and prevents diabetic nephropathy. However, the molecular mechanism of the synergistic effect of HOR and insulin needs to be elucidated. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells.

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Rogers, N M; Stephenson, M D; Kitching, A R; Horowitz, J D; Coates, P T H

2012-05-01

Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

In vivo imaging of cellular proliferation in renal cell carcinoma using 18F-fluorothymidine PET

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Wong, Peter K.; Lee, Sze Ting; Murone, Carmel; Eng, John; Lawrentschuk, Nathan; Berlangieri, Salvatore University; Pathmaraj, Kunthi; O’Keefe, Graeme J.; Sachinidis, John; Byrne, Amanda J.; Bolton, Damien M.; Davis, Ian D.; Scott, Andrew M.

2014-01-01

The ability to measure cellular proliferation non-invasively in renal cell carcinoma may allow prediction of tumour aggressiveness and response to therapy. The aim of this study was to evaluate the uptake of 18F-fluorothymidine (FLT) PET in renal cell carcinoma (RCC), and to compare this to 18F-fluorodeoxyglucose (FDG), and to an immunohistochemical measure of cellular proliferation (Ki-67). Twenty seven patients (16 male, 11 females; age 42-77) with newly diagnosed renal cell carcinoma suitable for resection were prospectively enrolled. All patients had preoperative FLT and FDG PET scans. Visual identification of tumour using FLT PET compared to normal kidney was facilitated by the use of a pre-operative contrast enhanced CT scan. After surgery tumour was taken for histologic analysis and immunohistochemical staining by Ki-67. The SUVmax (maximum standardized uptake value) mean±SD for FLT in tumour was 2.59±1.27, compared to normal kidney (2.47±0.34). The mean SUVmax for FDG in tumour was similar to FLT (2.60±1.08). There was a significant correlation between FLT uptake and the immunohistochemical marker Ki-67 (r=0.72, P<0.0001) in RCC. Ki-67 proliferative index was mean ± SD of 13.3%±9.2 (range 2.2% - 36.3%). There is detectable uptake of FLT in primary renal cell carcinoma, which correlates with cellular proliferation as assessed by Ki-67 labelling index. This finding has relevance to the use of FLT PET in molecular imaging studies of renal cell carcinoma biology

Isolated Late Metastasis of a Renal Cell Cancer Treated by Radical Distal Pancreatectomy

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J. P. Barras

1996-01-01

Full Text Available A 53–year-old man underwent right nephrectomy for a locally advanced renal cell carcinoma with concomitant resection of a solitary metastasis in the right lung. Ten years later, he presented with haematochezia caused by a tumour in the tail of pancreas, invading the transverse colon and the greater curvature of the stomach. The tumour was radically resected, and histological examination revealed a solitary metastasis of the previous renal cell carcinoma. This case illustrates a rare indication for pancreatic resection because of pancreatic metastasis.

Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

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Marcelo Zerati

2013-07-01

Full Text Available Introduction The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC is evolving, and Carbonic Anhydrase type IX (CA-IX has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1 overall survival, and 2 with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion. Materials and Methods This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS, TNM stage, tumor size (TS, Fuhrman nuclear grade (FNG, microvascular invasion (MVI, peri-renal fat invasion (PFI. We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: Th e mean follow-up time was 7.9 years (range 1.9 to 19.5 years. The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790; T stage (p = 0.179; tumor size (p = 0.143; grouped Fuhrman nuclear grade (p = 0.598; microvascular invasion (p = 0.685, and peri-renal fat invasion (p = 0.104. Conclusion Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma.

Specific estrogen-induced cell proliferation of cultured Syrian hamster renal proximal tubular cells in serum-free chemically defined media

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Oberley, T.D.; Lauchner, L.J.; Pugh, T.D.; Gonzalez, A.; Goldfarb, S.; Li, S.A.; Li, J.J.

1989-01-01

It has long been recognized that the renal proximal tubular epithelium of the hamster is a bona fide estrogen target tissue. The effect of estrogens on the growth of proximal tubule cell explants and dissociated single cells derived from these explant outgrowths has been studied in culture. Renal tubular cells were grown on a PF-HR-9 basement membrane under serum-free chemically defined culture conditions. At 7-14 days in culture, cell number was enhanced 3-fold in the presence of either 17β-estradiol or diethylstilbestrol. A similar 3-fold increase in cell number was also seen at 1 nM 17β-estradiol in subcultured dissociated single tubular cells derived from hamster renal tubular explant outgrowths at 21 days in culture. Concomitant exposure of tamoxifen at 3-fold molar excess in culture completely abolished the increase in cell number seen with 17β-estradiol. The proliferation effect of estrogens on proximal tubular cell growth appears to be species specific since 17β-estradiol did not alter the growth of either rat or guinea pig proximal tubules in culture. In addition, at 7-10 days in culture in the presence of 17β-estradiol, [ 3 H]thymidine labeling of hamster tubular cells was enhanced 3-fold. These results clearly indicate that estrogens can directly induce primary epithelial cell proliferation at physiologic concentrations and provide strong additional evidence for an important hormonal role in the neoplastic transformation of the hamster kidney

Microarray gene expression profiling and analysis in renal cell carcinoma

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Sadhukhan Provash

2004-06-01

Full Text Available Abstract Background Renal cell carcinoma (RCC is the most common cancer in adult kidney. The accuracy of current diagnosis and prognosis of the disease and the effectiveness of the treatment for the disease are limited by the poor understanding of the disease at the molecular level. To better understand the genetics and biology of RCC, we profiled the expression of 7,129 genes in both clear cell RCC tissue and cell lines using oligonucleotide arrays. Methods Total RNAs isolated from renal cell tumors, adjacent normal tissue and metastatic RCC cell lines were hybridized to affymatrix HuFL oligonucleotide arrays. Genes were categorized into different functional groups based on the description of the Gene Ontology Consortium and analyzed based on the gene expression levels. Gene expression profiles of the tissue and cell line samples were visualized and classified by singular value decomposition. Reverse transcription polymerase chain reaction was performed to confirm the expression alterations of selected genes in RCC. Results Selected genes were annotated based on biological processes and clustered into functional groups. The expression levels of genes in each group were also analyzed. Seventy-four commonly differentially expressed genes with more than five-fold changes in RCC tissues were identified. The expression alterations of selected genes from these seventy-four genes were further verified using reverse transcription polymerase chain reaction (RT-PCR. Detailed comparison of gene expression patterns in RCC tissue and RCC cell lines shows significant differences between the two types of samples, but many important expression patterns were preserved. Conclusions This is one of the initial studies that examine the functional ontology of a large number of genes in RCC. Extensive annotation, clustering and analysis of a large number of genes based on the gene functional ontology revealed many interesting gene expression patterns in RCC. Most

Role of everolimus in the treatment of renal cell carcinoma

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Saby George

2009-08-01

Full Text Available Saby George1, Ronald M Bukowski21University of Texas Health Sciences Center, MC-8221, Division of Hematology and Oncology, San Antonio, Texas, USA; 2CCF Lerner College of Medicine Division of Hematology and Oncology, Cleveland, Ohio, USAAbstract: The therapeutic options in metastatic renal cell carcinoma have been recently expanded by the discovery of the VHL gene, the mutation of which is associated with development of clear cell carcinoma, and overexpression of the angiogenesis pathway, resulting in a very vascular tumor. This breakthrough in science led to the development of a variety of small molecules inhibiting the VEGF-dependent angiogenic pathway, such as sunitinib and sorafenib. These agents prolong overall and progression-free survival, respectively. The result was the development of robust front-line therapies which ultimately fail and are associated with disease progression. In this setting, there existed an unmet need for developing second-line therapies for patients with refractory metastatic renal cell carcinoma (MRCC. Everolimus (RAD 001 is an oral inhibitor of the mammalian target of rapamycin (mTOR pathway. The double-blind, randomized, placebo-controlled phase III trial of everolimus (RECORD-1 conducted in MRCC patients after progression on sunitinib or sorafenib, or both, demonstrated a progression-free survival benefit favoring the study drug (4.9 months vs 1.9 months, HR 0.33, 95% CI 0.25 to 0.43, P ≤ 0 0.001. Everolimus thus established itself as a standard of care in the second-line setting for patients with MRCC who have failed treatment with VEGF receptor inhibitors.Keywords: mTOR inhibitor, mammalian target of rapamycin inhibitor, signal transduction inhibitor, renal cell carcinoma, targeted therapy

Diffusion-weighted imaging versus contrast-enhanced MR imaging for the differentiation of renal oncocytomas and chromophobe renal cell carcinomas

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Zhong, Yan; Wang, Haiyi; Shen, Yanguang; Ma, Lu; Pan, Jingjing; Ye, Huiyi [Chinese PLA General Hospital, Department of Radiology, Beijing (China); Guo, Aitao [Chinese PLA General Hospital, Department of Pathology, Beijing (China); Wang, Jia [Handan Central Hosptical, Department of Radiology, Hebei (China); Kang, Suhai [264 Hospital of PLA, X-ray Department, Taiyuan (China)

2017-12-15

To compare the performance of diffusion-weighted imaging (DWI) with that of contrast-enhanced MRI in differentiating renal oncocytomas from chromophobe renal cell carcinomas (RCCs). We recruited 48 patients with histopathologically confirmed renal oncocytomas (n=16) and chromophobe RCCs (n=32). All patients underwent preoperative DWI and contrast-enhanced MRI. Apparent diffusion coefficient (ADC) and signal intensity were measured in each patient. ADC ratio and percentage of signal intensity change were calculated. Mean ADC values for renal oncocytomas were significantly higher than those for chromophobe RCCs (1.59±0.21 vs. 1.09±0.29 x 10{sup -3} mm{sup 2}/s, p < 0.001). Area under the ROC curve, sensitivity and specificity were 0.931, 87.5% and 84.4%, respectively, for ADC measurement of DW imaging; 0.825, 87.5% and 75%, respectively, for enhancement ratio (p > 0.05). Adding ADC values to the enhancement ratios in the ROC, analysis to differentiate renal oncocytoma from chromophobe RCCs increased specificity from 75 to 87.5% at 87.5% sensitivity without significantly increasing the AUC (0.930). Both DWI and contrast-enhanced MRI may assist in differentiating renal oncocytomas from chromophobe RCCs, with DWI showing higher diagnostic value. The combination of the two parameters could potentially provide better performance in distinguishing these two tumours. (orig.)

Renal denervation prevents long-term sequelae of ischemic renal injury

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Kim, Jinu; Padanilam, Babu J.

2014-01-01

Signals that drive interstitial fibrogenesis after renal ischemia reperfusion injury remain undefined. Sympathetic activation is manifest even in the early clinical stages of chronic kidney disease and is directly related to disease severity. A role for renal nerves in renal interstitial fibrogenesis in the setting of ischemia reperfusion injury has not been studied. In male 129S1/SvImJ mice, ischemia reperfusion injury induced tubulointerstitial fibrosis as indicated by collagen deposition and profibrotic protein expression 4 to 16 days after the injury.. Leukocyte influx, proinflammatory protein expression, oxidative stress, apoptosis, and cell cycle arrest at G2/M phase were enhanced after ischemia reperfusion injury. Renal denervation at the time of injury or up to 1 day post-injury improved histology, decreased proinflammatory/profibrotic responses and apoptosis, and prevented G2/M cell cycle arrest in the kidney. Treatment with afferent nerve-derived calcitonin gene-related peptide (CGRP) or efferent nerve-derived norepinephrine in denervated and ischemia reperfusion injury-induced kidneys mimicked innervation, restored inflammation and fibrosis, induced G2/M arrest, and enhanced TGF-β1 activation. Blocking norepinephrine or CGRP function using respective receptor blockers prevented these effects. Consistent with the in vivo study, treatment with either norepinephrine or CGRP induced G2/M cell cycle arrest in HK-2 proximal tubule cells, whereas antagonists against their respective receptors prevented G2/M arrest. Thus, renal nerve stimulation is a primary mechanism and renal nerve-derived factors drive epithelial cell cycle arrest and the inflammatory cascade causing interstitial fibrogenesis after ischemia reperfusion injury. PMID:25207878

Renal Failure Associated with APECED and Terminal 4q Deletion: Evidence of Autoimmune Nephropathy

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Mohammed Al-Owain

2010-01-01

Full Text Available Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE. Terminal 4q deletion is also a rare cytogenetic abnormality that causes a variable syndrome of dysmorphic features, mental retardation, growth retardation, and heart and limb defects. We report a 12-year-old Saudi boy with mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical failure consistent with APECED. In addition, he has dysmorphic facial features, growth retardation, and severe global developmental delay. Patient had late development of chronic renal failure. The blastogenesis revealed depressed lymphocytes' response to Candida albicans at 38% when compared to control. Chromosome analysis of the patient revealed 46,XY,del(4(q33. FISH using a 4p/4q subtelomere DNA probe assay confirmed the deletion of qter subtelomere on chromosome 4. Parental chromosomes were normal. The deleted array was further defined using array CGH. AIRE full gene sequencing revealed a homozygous mutation namely 845_846insC. Renal biopsy revealed chronic interstitial nephritis with advanced fibrosis. In addition, there was mesangial deposition of C3, C1q, and IgM. This is, to the best of our knowledge, the first paper showing evidence of autoimmune nephropathy by renal immunofluorescence in a patient with APECED and terminal 4q deletion.