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https://www.readbyqxmd.com/read/28748411/the-role-of-von-willebrand-factor-in-thrombotic-microangiopathy
#1
REVIEW
Damien G Noone, Magdalena Riedl, Christoph Licht
Thrombotic microangiopathy (TMA) is caused by thrombus formation in the microvasculature. The disease spectrum of TMA includes, amongst others, thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS). TTP is caused by defective cleavage of von Willebrand factor (VWF), whereas aHUS is caused by overshooting complement activation and subsequent endothelial cell (EC) injury. Despite their distinct pathophysiology, the clinical manifestation of TTP and aHUS consisting of microangiopathic haemolytic anaemia and thrombocytopenia is often similar and difficult to distinguish...
July 26, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28737448/mast-cell-and-m1-macrophage-infiltration-and-local-pro-inflammatory-factors-were-attenuated-with-incretin-based-therapies-in-obesity-related-glomerulopathy
#2
Jiao He, Geheng Yuan, Fangxiao Cheng, Junqing Zhang, Xiaohui Guo
BACKGROUND: The global increase of obesity parallels the obesity-related glomerulopathy (ORG) epidemic. Dipeptidyl peptidase 4 inhibitors and glucagon-like peptide-1 receptor agonists were well recognized to attenuate renal injury independent of glucose control in diabetic nephropathy. There are limited studies focusing on their effects on ORG. We explored the effects of incretin-based therapies on early ORG and the inflammatory responses involved mainly concentrated on mast cell (MC) and macrophage (M) infiltration and local pro-inflammatory factors...
July 24, 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/28736029/protective-role-of-apelin-against-cyclosporine-induced-renal-tubular-injury-in-rats
#3
J S Kim, J W Yang, B G Han, H J Kwon, J H Kim, S O Choi
BACKGROUND: Cyclosporine (CsA) usually reduces glomerular filtration rate (GFR) but also can induce tubular injury without resulting in GFR reduction. Apelin is an endogenous ligand for the apelin receptor and has diverse physiologic roles related to hemodynamic or metabolic processes. We investigated the renoprotective role of apelin against CsA-induced tubular toxicity in rats. METHODS: Rats were given CsA (15 mg/kg/day) and/or apelin-13 (15 μg/kg/day) for 7 days via subcutaneous injection...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28718802/ouabain-protects-human-renal-cells-against-the-cytotoxic-effects-of-shiga-toxin-type-2-and-subtilase-cytotoxin
#4
María M Amaral, Magalí C Girard, Romina S Álvarez, Adrienne W Paton, James C Paton, Horacio A Repetto, Flavia Sacerdoti, Cristina A Ibarra
Hemolytic uremic syndrome (HUS) is one of the most common causes of acute renal failure in children. The majority of cases are associated with Shiga toxin (Stx)-producing Escherichia coli (STEC). In Argentina, HUS is endemic and presents the highest incidence rate in the world. STEC strains expressing Stx type 2 (Stx2) are responsible for the most severe cases of this pathology. Subtilase cytotoxin (SubAB) is another STEC virulence factor that may contribute to HUS pathogenesis. To date, neither a licensed vaccine nor effective therapy for HUS is available for humans...
July 18, 2017: Toxins
https://www.readbyqxmd.com/read/28696246/farnesoid-x-receptor-agonism-protects-against-diabetic-tubulopathy-potential-add-on-therapy-for-diabetic-nephropathy
#5
Andi Marquardt, Moh'd Mohanad Al-Dabet, Sanchita Ghosh, Shrey Kohli, Jayakumar Manoharan, Ahmed ElWakiel, Ihsan Gadi, Fabian Bock, Sumra Nazir, Hongjie Wang, Jonathan A Lindquist, Peter Paul Nawroth, Thati Madhusudhan, Peter R Mertens, Khurrum Shahzad, Berend Isermann
Established therapies for diabetic nephropathy (dNP) delay but do not prevent its progression. The shortage of established therapies may reflect the inability to target the tubular compartment. The chemical chaperone tauroursodeoxycholic acid (TUDCA) ameliorates maladaptive endoplasmic reticulum (ER) stress signaling and experimental dNP. Additionally, TUDCA activates the farnesoid X receptor (FXR), which is highly expressed in tubular cells. We hypothesized that TUDCA ameliorates maladaptive ER signaling via FXR agonism specifically in tubular cells...
July 10, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28687535/endothelial-nf-%C3%AE%C2%BAb-blockade-abrogates-anca-induced-gn
#6
Mira Choi, Adrian Schreiber, Claudia Eulenberg-Gustavus, Claus Scheidereit, Jan Kamps, Ralph Kettritz
ANCA-associated vasculitis (AAV) is a highly inflammatory condition in which ANCA-activated neutrophils interact with the endothelium, resulting in necrotizing vasculitis. We tested the hypothesis that endothelial NF-κB mediates necrotizing crescentic GN (NCGN) and provides a specific treatment target. Reanalysis of kidneys from previously examined murine NCGN disease models revealed NF-κB activation in affected kidneys, mostly as a p50/p65 heterodimer, and increased renal expression of NF-κB-dependent tumor necrosis factor α (TNF-α)...
July 7, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28685678/glomerular-endothelium-and-its-impact-on-glomerular-filtration-barrier-in-diabetes-are-the-gaps-still-illusive
#7
Joseph Fomusi Ndisang
BACKGROUND: Glomerular capillaries are lined with highly specialized fenestrated endothelium which are primarily responsible to regulate high flux filtration of fluid and small solutes. During filtration, plasma passes through the fenestrated endothelium and basement membrane before it reaches the slit diaphragm, a specialized type of intercellular junction that connects neighbouring podocytes. METHODS: A PubMed search was done for recent articles on components of the glomerular filtration barrier such as glomerular endothelial cells, podocytes and glomerular basement membrane, and the effect of diabetes on these structures...
July 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28682034/-fabry-s-disease-an-example-of-cardiorenal-syndrome-type-5
#8
Gianluca Villa, Stefano Romagnoli, Aashish Sharma, Claudio Ronco
Fabry's disease (FD) is a severe congenital metabolic disorder characterized by the deficient activity of lysosomal exoglycohydrolase alpha-galactosidase, characterized by glycosphingolipid deposition in several cells, such as capillary endothelial cells, renal, cardiac, and nerve cells. As a systemic disease leading to a contemporaneous myocardial and renal dysfunction, FD might be an example of cardiorenal syndrome type 5 (CRS-5). Kidney damage is commonly characterized by proteinuria, isosthenuria and altered tubular function when occurs at the second-third decade, azotemia and end-stage renal disease in third-fifth decade...
March 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28676023/vascular-endothelial-growth-factor-inhibitor-therapy-and-cardiovascular-and-renal-damage-in-renal-cell-carcinoma
#9
Silvia Lai, Alessio Molfino, Patrizia Seminara, Flavia Longo, Georgie Innico, Bettina Coppola, Daniela Mastroluca, Alessandro Galani, Mira Dimko, Paola Aceto, Carlo Lai
BACKGROUND: Sunitinib, a tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF), is approved for first and second line treatment of advanced renal cell carcinoma (RCC). Knowledge on the effects of sunitinib on cardiovascular (CV) risk and renal damage is limited. AIM: To evaluate possible renal and CV damage in patients with RCC treated with sunitinib. MATERIALS AND METHODS: Patients with metastatic RCC treated with sunitinib were enrolled...
June 20, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28674043/beneficial-effects-of-systemically-administered-human-muse-cells-in-adriamycin-nephropathy
#10
Nao Uchida, Yoshihiro Kushida, Masaaki Kitada, Shohei Wakao, Naonori Kumagai, Yasumasa Kuroda, Yoshiaki Kondo, Yukari Hirohara, Shigeo Kure, Gregorio Chazenbalk, Mari Dezawa
Multilineage-differentiating stress-enduring (Muse) cells are nontumorigenic endogenous pluripotent-like stem cells that can be collected from various organs. Intravenously administered Muse cells have been shown to spontaneously migrate to damaged tissue and replenish lost cells, but the effect in FSGS is unknown. We systemically administered human bone marrow-derived Muse cells without concurrent administration of immunosuppressants to severe combined immune-deficient (SCID) and BALB/c mouse models with adriamycin-induced FSGS (FSGS-SCID and FSGS-BALB/c, respectively)...
July 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28665887/serum-podocalyxin-is-significantly-increased-in-early-onset-preeclampsia-and-may-represent-a-novel-marker-of-maternal-endothelial-cell-dysfunction
#11
Qi Chen, Yao Wang, Ying Li, Min Zhao, Guiying Nie
OBJECTIVE: Podocalyxin is a glomerular podocyte protein and increased in urine of preeclampsia. However, podocalyxin is also expressed in endothelial cells of other organs. Here we investigated whether podocalyxin is detectable in pregnant serum and whether the levels are altered in preeclampsia. METHODS: Podocalyxin was determined by ELISA in sera collected from normal pregnancy across gestation (n = 44) and from preeclamptic pregnancies at diagnosis (n = 34) with gestation-age-matched controls (n = 68)...
June 29, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28664407/combined-use-of-electron-microscopy-and-intravital-imaging-captures-morphological-and-functional-features-of-podocyte-detachment
#12
REVIEW
James L Burford, Georgina Gyarmati, Isao Shirato, Wilhelm Kriz, Kevin V Lemley, János Peti-Peterdi
The development of podocyte injury and albuminuria in various glomerular pathologies is still incompletely understood due to technical limitations in studying the glomerular filtration barrier (GFB) in real-time. We aimed to directly visualize the early morphological and functional changes of the GFB during the development of focal segmental glomerulosclerosis (FSGS) using a combination of transmission electron microscopy (TEM) and in vivo multiphoton microscopy (MPM) in the rat puromycin aminonucleoside (PAN) model...
June 29, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28659030/tongxinluo-inhibits-renal-fibrosis-in-diabetic-nephropathy-involvement-of-the-suppression-of-intercellular-transfer-of-tgf-formula-see-text-1-containing-exosomes-from-gecs-to-gmcs
#13
Xiao-Ming Wu, Yan-Bin Gao, Li-Ping Xu, Da-Wei Zou, Zhi-Yao Zhu, Xiao-Lei Wang, Wei-Jie Yao, Liang-Tao Luo, Yu Tong, Nian-Xiu Tian, Zhe-Ji Han, Wan-Yu Dang
Glomerular mesangial cells (GMCs) activation is implicated in the pathogenesis of diabetic nephropathy (DN). Our previous study revealed that high glucose (HG)-treated glomerular endothelial cells (GECs) produce an increased number of TGF-β1-containing exosomes to activate GMCs through the TGF-β1/Smad3 signaling pathway. We also identified that Tongxinluo (TXL), a traditional Chinese medicine, has beneficial effects on the treatment of DN in DN patients and type 2 diabetic mice. However, it remained elusive whether TXL could ameliorate renal structure and function through suppression of intercellular transfer of TGF-β1-containing exosomes from GECs to GMCs...
June 28, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28652884/drug-absorption-related-nephrotoxicity-assessment-on-an-intestine-kidney-chip
#14
Zhongyu Li, Wentao Su, Yujuan Zhu, Tingting Tao, Dong Li, Xiaojun Peng, Jianhua Qin
Drug absorption in the intestine is tightly related to drug-induced nephrotoxicity, which is a relatively common side effect in clinical practice. It highlights a great need to develop predictive models with high accuracy in the early stage during new drug discovery and development. Herein, we presented a novel intestine-kidney chip, which recapitulated drug absorption in the intestine and its resultant drug toxicity on the kidney. This work aims to provide an integrated tool for accurate assessment of drug absorption-related nephrotoxicity in vitro...
May 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/28647211/tubuloreticular-inclusions-in-peritubular-capillaries-of-renal-allografts
#15
Jee Youn Lee, Seung Hwan Song, Yu Seun Kim, Beom Jin Lim, Soon Il Kim, Myoung Soo Kim, Hyeon Joo Jeong
BACKGROUND: Tubuloreticular inclusions (TRIs) are anastomosing networks of microtubules that are frequently found in autoimmune diseases and viral infections. In renal allografts, TRIs have been reported in glomerular endothelial cells in association with viral infections and donor specific antibodies (DSAs), but their presence in peritubular capillaries has not been explored. METHODS: We collected seven cases with TRIs out of 148 consecutive renal allograft biopsies taken from Dec...
June 6, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28617168/renalase-assessment-with-regard-to-kidney-function-lipid-disturbances-and-endothelial-dysfunction-parameters-in-stable-renal-transplant-recipients
#16
Dijana Stojanovic, Tatjana Cvetkovic, Miodrag Stojanovic, Nikola Stefanovic, Radmila Velickovic-Radovanovic, Natasa Zivkovic
BACKGROUND: Renal transplant dysfunction has been shown to be independent predictor for premature cardiovascular disease and mortality. Renalase, a flavoprotein secreted by several tissues, including the kidney, has been found to regulate sympathetic tone and blood pressure. The purpose of this secondary analysis was to explore relationships among parameters of endothelial dysfunction, lipids, glomerular filtration rate, and renalase in 2 groups: renal transplant patients with controlled hypertension and healthy volunteers...
June 2017: Progress in Transplantation
https://www.readbyqxmd.com/read/28587670/high-mobility-group-box-1-contributes-to-anti-myeloperoxidase-antibody-induced-glomerular-endothelial-cell-injury-through-a-moesin-dependent-route
#17
Hui Deng, Chen Wang, Dong-Yuan Chang, Nan Hu, Min Chen, Ming-Hui Zhao
BACKGROUND: Our previous study found that circulating and urinary levels of high mobility group box-1 (HMGB1) were closely associated with disease activity in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Moreover, HMGB1 participates in ANCA-induced neutrophil activation. Cross-reactivity between moesin and anti-myeloperoxidase (MPO) antibody has been reported in both human and mouse. The current study investigated whether HMGB1 participated in MPO-ANCA-induced glomerular endothelial cell (GEnC) injury, which is one of the most important aspects in the pathogenesis of AAV...
June 6, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28584258/cathepsin-s-inhibition-combines-control-of-systemic-and-peripheral-pathomechanisms-of-autoimmune-tissue-injury
#18
Maia Tato, Santhosh V Kumar, Yajuan Liu, Shrikant R Mulay, Solange Moll, Bastian Popper, Jonathan N Eberhard, Dana Thomasova, Arne Christian Rufer, Sabine Gruner, Wolfgang Haap, Guido Hartmann, Hans-Joachim Anders
Cathepsin(Cat)-S processing of the invariant chain-MHC-II complex inside antigen presenting cells is a central pathomechanism of autoimmune-diseases. Additionally, Cat-S is released by activated-myeloid cells and was recently described to activate protease-activated-receptor-(PAR)-2 in extracellular compartments. We hypothesized that Cat-S blockade targets both mechanisms and elicits synergistic therapeutic effects on autoimmune tissue injury. MRL-(Fas)lpr mice with spontaneous autoimmune tissue injury were treated with different doses of Cat-S inhibitor RO5459072, mycophenolate mofetil or vehicle...
June 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28584011/regulatory-t-cell-augmentation-or-interleukin-17-inhibition-prevents-calcineurin-inhibitor-induced-hypertension-in-mice
#19
Valorie L Chiasson, Abhinandan R Pakanati, Marcos Hernandez, Kristina J Young, Kelsey R Bounds, Brett M Mitchell
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...
July 2017: Hypertension
https://www.readbyqxmd.com/read/28579836/update-on-the-renal-toxicity-of-iodinated-contrast-drugs-used-in-clinical-medicine
#20
REVIEW
Michele Andreucci, Teresa Faga, Raffaele Serra, Giovambattista De Sarro, Ashour Michael
An important side effect of diagnostic contrast drugs is contrast-induced acute kidney injury (CI-AKI; a sudden decrease in renal function) occurring 48-72 hours after injection of a contrast drug that cannot be attributed to other causes. Its existence has recently been challenged, because of some retrospective studies in which the incidence of AKI was not different between subjects who received a contrast drug and those who did not, even using propensity score matching to prevent selection bias. For some authors, only patients with estimated glomerular filtration rate <30 mL/min/1...
2017: Drug, Healthcare and Patient Safety
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