Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/24909663http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24909663http://www.w3.org/2000/01/rdf-schema#comment"The pathogenesis and therapy of Shigatoxin 2 (Stx2)-mediated kidney failure remain controversial. Our aim was to test whether, during an infection with Stx2-producing E. coli (STEC), Stx2 exerts direct effects on renal tubular epithelium and thereby possibly contributes to acute renal failure. Mice represent a suitable model because they, like humans, express the Stx2-receptor Gb3 in the tubular epithelium but, in contrast to humans, not in glomerular endothelia, and are thus free of glomerular thrombotic microangiopathy (TMA). In wild-type mice, Stx2 caused acute tubular dysfunction with consequent electrolyte disturbance, which was most likely the cause of death. Tubule-specific depletion of Gb3 protected the mice from acute renal failure. In vitro, Stx2 induced secretion of proinflammatory cytokines and apoptosis in human tubular epithelial cells, thus implicating a direct effect of Stx2 on the tubular epithelium. To correlate these results to human disease, kidney biopsies and outcome were analysed in patients with Stx2-associated kidney failure (n = 11, aged 22-44 years). The majority of kidney biopsies showed different stages of an ongoing TMA; however, no glomerular complement activation could be demonstrated. All biopsies, including those without TMA, showed severe acute tubular damage. Due to these findings, patients were treated with supportive therapy without complement-inhibiting antibodies (eculizumab) or immunoadsorption. Despite the severity of the initial disease [creatinine 6.34 (1.31-17.60) mg/dl, lactate dehydrogenase 1944 (753-2792) U/l, platelets 33 (19-124)/nl and haemoglobin 6.2 (5.2-7.8) g/dl; median (range)], all patients were discharged after 33 (range 19-43) days with no neurological symptoms and no dialysis requirement [creatinine 1.39 (range 0.84-2.86) mg/dl]. The creatinine decreased further to 0.90 (range 0.66-1.27) mg/dl after 24 months. Based on these data, one may surmise that acute tubular damage represents a separate pathophysiological mechanism, importantly contributing to Stx2-mediated acute kidney failure. Specifically in young adults, an excellent outcome can be achieved by supportive therapy only."xsd:string
http://purl.uniprot.org/citations/24909663http://purl.org/dc/terms/identifier"doi:10.1002/path.4388"xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/author"Geiger H."xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/author"Grone H.J."xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/author"Porubsky S."xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/author"Betz C."xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/author"Gretz N."xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/author"Obermuller N."xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/author"Muthing J."xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/author"Buttner S."xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/author"Jung O."xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/author"Jennemann R."xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/author"Federico G."xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/author"Hauser I.A."xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/author"Grone E."xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/name"J Pathol"xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/pages"120-133"xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/title"Direct acute tubular damage contributes to Shigatoxin-mediated kidney failure."xsd:string
http://purl.uniprot.org/citations/24909663http://purl.uniprot.org/core/volume"234"xsd:string
http://purl.uniprot.org/citations/24909663http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24909663
http://purl.uniprot.org/citations/24909663http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/24909663
http://purl.uniprot.org/uniprot/#_A0A2R8VI36-mappedCitation-24909663http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24909663
http://purl.uniprot.org/uniprot/#_A2AIU6-mappedCitation-24909663http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24909663
▶