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  • 1
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    Online Resource
    The ADF/Cofilin-Pathway and Actin Dynamics in Podocyte Injury
    Hindawi Limited ; 2012
    In:  International Journal of Cell Biology Vol. 2012 ( 2012), p. 1-8
    Details
    In: International Journal of Cell Biology, Hindawi Limited, Vol. 2012 ( 2012), p. 1-8
    Abstract: ADF/cofilins are the major regulators of actin dynamics in mammalian cells. The activation of ADF/cofilins is controlled by a variety of regulatory mechanisms. Dysregulation of ADF/cofilin may result in loss of a precisely organized actin cytoskeletal architecture and can reduce podocyte migration and motility. Recent studies suggest that cofilin-1 can be regulated through several extracellular signals and slit diaphragm proteins. Cofilin knockdown and knockout animal models show dysfunction of glomerular barrier and filtration with foot process effacement and loss of secondary foot processes. This indicates that cofilin-1 is necessary for modulating actin dynamics in podocytes. Podocyte alterations in actin architecture may initiate or aid the progression of a large variety of glomerular diseases, and cofilin activity is required for reorganization of an intact filtration barrier. Since almost all proteinuric diseases result from a similar phenotype with effacement of the foot processes, we propose that cofilin-1 is at the centre stage of the development of proteinuria and thus may be an attractive drug target for antiproteinuric treatment strategies.
    Type of Medium: Online Resource
    ISSN: 1687-8876 , 1687-8884
    URL: Article
    DOI: 10.1155/2012/320531
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2012
    detail.hit.zdb_id: 2536742-0
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  • 2
    Online Resource
    Online Resource
    Urinary NGAL Ratio Is Not a Sensitive Biomarker for Monitoring Acute Tubular Injury in Kidney Transplant Patients: NGAL and ATI in Renal Transplant Patients
    Hindawi Limited ; 2012
    In:  Journal of Transplantation Vol. 2012 ( 2012), p. 1-8
    Details
    In: Journal of Transplantation, Hindawi Limited, Vol. 2012 ( 2012), p. 1-8
    Abstract: Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is known to predict the prolonged delayed graft function after kidney transplantation. We examined the relation of uNGAL with histological findings of acute tubular injury (ATI). Analyses were made in biopsies taken at 6 weeks, 3 months, and 6 months after kidney transplantation. uNGAL was measured in the spot urines, normalized to urinary creatinine excretion, and correlated to biopsy findings and clinical, laboratory, and demographic variables. Controls included healthy individuals, individuals after kidney donation and ICU patients with acute kidney failure. Renal transplant recipients without ATI did not display elevated uNGAL levels compared to the healthy controls. Transplant patients with ATI had a higher uNGAL excretion at 6 weeks than patients without ATI (27,435 versus 13,605 ng/g; P = 0.031 ). This increase in uNGAL was minor compared to ICU patients with acute renal failure ( 2.05 × 106  ng/g). Patients with repeated findings of ATI or severe ATI did not have higher urinary NGAL levels compared to those with only one ATI finding or moderate ATI. Female recipient gender and urinary tract infection were identified as potential confounders. uNGAL has a relation with histological signs of acute tubular injury. The usability of this biomarker in renal allograft recipients is limited because of the low sensitivity.
    Type of Medium: Online Resource
    ISSN: 2090-0007 , 2090-0015
    URL: Article
    DOI: 10.1155/2012/563404
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2012
    detail.hit.zdb_id: 2503421-2
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  • 3
    Online Resource
    Online Resource
    “Zebrafishing” for Novel Genes Relevant to the Glomerular Filtration Barrier
    Hindawi Limited ; 2013
    In:  BioMed Research International Vol. 2013 ( 2013), p. 1-12
    Details
    In: BioMed Research International, Hindawi Limited, Vol. 2013 ( 2013), p. 1-12
    Abstract: Data for genes relevant to glomerular filtration barrier function or proteinuria is continually increasing in an era of microarrays, genome-wide association studies, and quantitative trait locus analysis. Researchers are limited by published literature searches to select the most relevant genes to investigate. High-throughput cell cultures and other in vitro systems ultimately need to demonstrate proof in an in vivo model. Generating mammalian models for the genes of interest is costly and time intensive, and yields only a small number of test subjects. These models also have many pitfalls such as possible embryonic mortality and failure to generate phenotypes or generate nonkidney specific phenotypes. Here we describe an in vivo zebrafish model as a simple vertebrate screening system to identify genes relevant to glomerular filtration barrier function. Using our technology, we are able to screen entirely novel genes in 4–6 weeks in hundreds of live test subjects at a fraction of the cost of a mammalian model. Our system produces consistent and reliable evidence for gene relevance in glomerular kidney disease; the results then provide merit for further analysis in mammalian models.
    Type of Medium: Online Resource
    ISSN: 2314-6133 , 2314-6141
    URL: Article
    DOI: 10.1155/2013/658270
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2013
    detail.hit.zdb_id: 2698540-8
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  • 4
    Online Resource
    Online Resource
    Antiphospholipase A 2 Receptor Autoantibodies: A Comparison of Three Different Immunoassays for the Diagnosis of Idiopathic Membranous Nephropathy
    Hindawi Limited ; 2014
    In:  Journal of Immunology Research Vol. 2014 ( 2014), p. 1-5
    Details
    In: Journal of Immunology Research, Hindawi Limited, Vol. 2014 ( 2014), p. 1-5
    Abstract: Background . The recent identification of circulating autoantibodies directed towards the M-type phospholipase A 2 receptor (PLA 2 R) has been a major advancement in the serological diagnosis of idiopathic membranous nephropathy (IMN), a common cause of nephrotic syndrome in adults. The goal of this study was to compare the performance characteristics of two commercial assays as well as the first addressable laser bead immunoassay (ALBIA) developed for the detection of anti-PLA 2 R antibodies. Methods. Serum samples of 157 IMN patients and 142 controls were studied. Samples were tested by a cell based immunofluorescence assay (CBA-IFA, Euroimmun, Germany), by ELISA (Euroimmun), and by a novel ALBIA employing an in vivo expressed recombinant human PLA 2 R. Results . Overall, the three assays showed significant qualitative and quantitative correlation. As revealed by receiver operating characteristic analysis, the ALBIA correlated better with the CBA-IFA than the ELISA ( P = 0.0003 ). The clinical sensitivities/specificities for IMN were 60.0% (51.0–68.5%)/98.6% (95.0–99.8%) and 56.2% (47.2–64.8%)/100.0% (97.4–100.0%) for ALBIA and CBA-IFA, respectively. Conclusion . The ALBIA represents a promising assay for the detection of anti-PLA 2 R antibodies showing similar performance to the CBA-IFA and the advantage of ease of use and suitability for high throughput, rapid turnaround times, and multiplexing.
    Type of Medium: Online Resource
    ISSN: 2314-8861 , 2314-7156
    URL: Article
    DOI: 10.1155/2014/143274
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2014
    detail.hit.zdb_id: 2817541-4
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  • 5
    Online Resource
    Online Resource
    Renal Involvement in Preeclampsia: Similarities to VEGF Ablation Therapy
    Hindawi Limited ; 2011
    In:  Journal of Pregnancy Vol. 2011 ( 2011), p. 1-6
    Details
    In: Journal of Pregnancy, Hindawi Limited, Vol. 2011 ( 2011), p. 1-6
    Abstract: Glomerular VEGF expression is critical for the maintenance and function of an intact filtration barrier. Alterations in glomerular VEGF bioavailability result in endothelial as well as in podocyte damage. Renal involvement in preeclampsia includes proteinuria, podocyturia, elevated blood pressure, edema, glomerular capillary endotheliosis, and thrombotic microangiopathy. At least the renal signs, symptoms, and other evidence can sufficiently be explained by reduced VEGF levels. The aim of this paper was to summarize our pathophysiological understanding of the renal involvement of preeclampsia and point out similarities to the renal side effects of VEGF-ablation therapy.
    Type of Medium: Online Resource
    ISSN: 2090-2727 , 2090-2735
    URL: Article
    DOI: 10.1155/2011/176973
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2011
    detail.hit.zdb_id: 2595413-1
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  • 6
    Online Resource
    Online Resource
    Involvement of Angiopoietin-2 and Tie2 Receptor Phosphorylation in STEC-HUS Mediated by Escherichia coli O104:H4
    Hindawi Limited ; 2015
    In:  Mediators of Inflammation Vol. 2015 ( 2015), p. 1-7
    Details
    In: Mediators of Inflammation, Hindawi Limited, Vol. 2015 ( 2015), p. 1-7
    Abstract: Escherichia coli O104:H4-associated hemolytic uremic syndrome (HUS) is characterized by Shiga toxin-induced vascular damage. As indicated by recent studies, dysregulation of the angiopoietin (Angpt)/Tie2 ligand receptor system may be crucial for endothelial dysfunction in HUS. Early Angpt-2 levels quantified in 48 adult HUS patients were predictive for a complicated clinical course, in particular for need of hemodialysis and mechanical ventilation as well as occurrence of seizures. In vitro challenge of human umbilical vein endothelial cells with patients’ sera indicated an injurious mediator role of Angpt-2 opening future perspectives for mitigating endothelial activation in HUS.
    Type of Medium: Online Resource
    ISSN: 0962-9351 , 1466-1861
    URL: Article
    DOI: 10.1155/2015/670248
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2015
    detail.hit.zdb_id: 2008065-7
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  • 7
    Online Resource
    Online Resource
    Kinetics of Rituximab Excretion into Urine and Peritoneal Fluid in Two Patients with Nephrotic Syndrome
    Hindawi Limited ; 2017
    In:  Case Reports in Nephrology Vol. 2017 ( 2017), p. 1-8
    Details
    In: Case Reports in Nephrology, Hindawi Limited, Vol. 2017 ( 2017), p. 1-8
    Abstract: Clinical observations suggest that treatment of Rituximab might be less effective in patients with nephrotic range proteinuria when compared to nonnephrotic patients. It is conceivable that the reason for this is that significant amounts of Rituximab might be lost in the urine in a nephrotic patient and that these patients require a repeated or higher dosage. However, this has not been systematically studied. In this case report we describe two different patients with nephrotic range proteinuria receiving Rituximab. The first patient received Rituximab for therapy resistant cryoglobulinemic membranoproliferative glomerulonephritis and the other for second line treatment of Felty’s syndrome. We employed flow cytometry to determine the amount of Rituximab excretion in both urine and peritoneal fluid specimens in these patients following administration of Rituximab. We found that a significant amount of Rituximab is lost from the circulation by excretion into the urine. Furthermore we saw a close correlation of the excretion of Rituximab to the excretion of IgG molecules suggesting selectivity of proteinuria as the determining factor of Rituximab excretion. Further larger scale clinical studies could have the potential to evaluate an optimal cut-off value of IgG urinary loss before a possible administration of Rituximab therefore contributing to a more individualized treatment approach in patients with nonselective and nephrotic range proteinuria.
    Type of Medium: Online Resource
    ISSN: 2090-6641 , 2090-665X
    URL: Article
    DOI: 10.1155/2017/1372859
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2017
    detail.hit.zdb_id: 2627652-5
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