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  • 1
    Online-Ressource
    Online-Ressource
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Clinical Journal of the American Society of Nephrology Vol. 11, No. 5 ( 2016-5), p. 761-769
    In: Clinical Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 11, No. 5 ( 2016-5), p. 761-769
    Kurzfassung: Hypervolemia is a common feature of patients with CKD and associated with hypertension. Recent work has shown stimulation of sodium retention by urinary plasmin during nephrotic syndrome. However, it is unclear whether plasminuria plays a role in patients with stable CKD and non-nephrotic proteinuria. Design, setting, participants, & measurements In this cross-sectional study, we analyzed the fluid status of 171 patients with CKD consecutively presenting to our outpatient clinic from 2012 to 2013 using bioimpedance spectroscopy (Body Composition Monitor [BCM]; Fresenius Medical Care, Germany) and its associations to the urinary excretion of plasminogen and plasmin from a spot urine sample. Two–electrode voltage clamp measurements were performed in Xenopus laevis oocytes expressing human epithelial sodium channel to investigate whether plasmin in concentrations found in urine can activate the channel. Results Overhydration 〉 5% and overhydration 〉 10% of the extracellular volume were found in 29% and 17% of the patients, respectively, and overhydration was associated with edema, hypertension, higher stages of CKD, and proteinuria. Proteinuria was the strongest independent predictor for overhydration (+0.58 L/1.73 m 2 per 10-fold increase; P 〈 0.001). Urinary excretion of plasmin(ogen) quantified by ELISA correlated strongly with proteinuria ( r =0.87) and overhydration ( r =0.47). Using a chromogenic substrate, active plasmin was found in 44% of patients and correlated with proteinuria and overhydration. Estimated urinary plasmin concentrations were in a range sufficient to activate epithelial sodium channel currents in vitro . In multivariable analysis, urinary excretion of plasmin(ogen) was associated with overhydration similar to proteinuria. Conclusions Hypervolemia in patients with CKD is strongly associated with proteinuria, even in the non-nephrotic range. Protein-rich urine contains high amounts of plasminogen and active plasmin, rendering plasminuria as a possible link between proteinuria and hypervolemia.
    Materialart: Online-Ressource
    ISSN: 1555-9041 , 1555-905X
    Sprache: Englisch
    Verlag: Ovid Technologies (Wolters Kluwer Health)
    Publikationsdatum: 2016
    ZDB Id: 2216582-4
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    In: Journal of Biological Chemistry, Elsevier BV, Vol. 289, No. 27 ( 2014-07), p. 19067-19078
    Materialart: Online-Ressource
    ISSN: 0021-9258
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2014
    ZDB Id: 2141744-1
    ZDB Id: 1474604-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Journal of General Physiology, Rockefeller University Press, Vol. 152, No. 8 ( 2020-08-03)
    Kurzfassung: Prostaglandin E2 (PGE2) is the most abundant prostanoid in the kidney, affecting a wide range of renal functions. Conflicting data have been reported regarding the effects of PGE2 on tubular water and ion transport. The amiloride-sensitive epithelial sodium channel (ENaC) is rate limiting for transepithelial sodium transport in the aldosterone-sensitive distal nephron. The aim of the present study was to explore a potential role of PGE2 in regulating ENaC in cortical collecting duct (CCD) cells. Short-circuit current (ISC) measurements were performed using the murine mCCDcl1 cell line known to express characteristic properties of CCD principal cells and to be responsive to physiological concentrations of aldosterone and vasopressin. PGE2 stimulated amiloride-sensitive ISC via basolateral prostaglandin E receptors type 4 (EP4) with an EC50 of ∼7.1 nM. The rapid stimulatory effect of PGE2 on ISC resembled that of vasopressin. A maximum response was reached within minutes, coinciding with an increased abundance of β-ENaC at the apical plasma membrane and elevated cytosolic cAMP levels. The effects of PGE2 and vasopressin were nonadditive, indicating similar signaling cascades. Exposing mCCDcl1 cells to aldosterone caused a much slower (∼2 h) increase of the amiloride-sensitive ISC. Interestingly, the rapid effect of PGE2 was preserved even after aldosterone stimulation. Furthermore, application of arachidonic acid also increased the amiloride-sensitive ISC involving basolateral EP4 receptors. Exposure to arachidonic acid resulted in elevated PGE2 in the basolateral medium in a cyclooxygenase 1 (COX-1)–dependent manner. These data suggest that in the cortical collecting duct, locally produced and secreted PGE2 can stimulate ENaC-mediated transepithelial sodium transport.
    Materialart: Online-Ressource
    ISSN: 0022-1295 , 1540-7748
    Sprache: Englisch
    Verlag: Rockefeller University Press
    Publikationsdatum: 2020
    ZDB Id: 1477246-2
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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