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Endothelial and epithelial barrier function is crucial for the maintenance of physiological processes. The barrier paracellular permeability depends on the composition and spatial distribution of the cell-to-cell tight junctions (TJ). Here, we provide an experimental workflow that yields several layers of physiological data in the setting of a single endothelial cell monolayer. Human umbilical vein endothelial cells were grown on Transwell filters. Transendothelial electrical resistance (TER) and 10 kDa FITC dextran flux were measured using Alanyl-Glutamine (AlaGln) as a paracellular barrier modulator. Single monolayers were immunolabelled for Zonula Occludens-1 (ZO-1) and Claudin-5 (CLDN5) and used for automated immunofluorescence imaging. Finally, the same monolayers were used for single molecule localization microscopy (SMLM) of ZO-1 and CLDN5 at the nanoscale for spatial clustering analysis. The TER increased and the paracellular dextran flux decreased after the application of AlaGln and these functional changes of the monolayer were mediated by an increase in the ZO-1 and CLDN5 abundance in the cell–cell interface. At the nanoscale level, the functional and protein abundance data were accompanied by non-random increased clustering of CLDN5. Our experimental workflow provides multiple data from a single monolayer and has wide applicability in the setting of paracellular studies in endothelia and epithelia.
Maria Bartosova; David Ridinger; Iva Marinovic; Jana Heigwer; Conghui Zhang; Eszter Levai; Jens Westhoff; Franz Schaefer; Stefan Terjung; Georg Hildenbrand; Damir Krunic; Felix Bestvater; Michael Hausmann; Claus Schmitt; Sotirios Zarogiannis. An Experimental Workflow for Studying Barrier Integrity, Permeability, and Tight Junction Composition and Localization in a Single Endothelial Cell Monolayer: Proof of Concept. International Journal of Molecular Sciences 2021, 22, 8178 .
AMA StyleMaria Bartosova, David Ridinger, Iva Marinovic, Jana Heigwer, Conghui Zhang, Eszter Levai, Jens Westhoff, Franz Schaefer, Stefan Terjung, Georg Hildenbrand, Damir Krunic, Felix Bestvater, Michael Hausmann, Claus Schmitt, Sotirios Zarogiannis. An Experimental Workflow for Studying Barrier Integrity, Permeability, and Tight Junction Composition and Localization in a Single Endothelial Cell Monolayer: Proof of Concept. International Journal of Molecular Sciences. 2021; 22 (15):8178.
Chicago/Turabian StyleMaria Bartosova; David Ridinger; Iva Marinovic; Jana Heigwer; Conghui Zhang; Eszter Levai; Jens Westhoff; Franz Schaefer; Stefan Terjung; Georg Hildenbrand; Damir Krunic; Felix Bestvater; Michael Hausmann; Claus Schmitt; Sotirios Zarogiannis. 2021. "An Experimental Workflow for Studying Barrier Integrity, Permeability, and Tight Junction Composition and Localization in a Single Endothelial Cell Monolayer: Proof of Concept." International Journal of Molecular Sciences 22, no. 15: 8178.
Emerging evidence indicates that the dysregulation of cellular redox homeostasis and chronic inflammatory processes are implicated in the pathogenesis of kidney and brain disorders. In this light, endogenous dipeptide carnosine (β-alanyl-L-histidine) and hydrogen sulfide (H2S) exert cytoprotective actions through the modulation of redox-dependent resilience pathways during oxidative stress and inflammation. Several recent studies have elucidated a functional crosstalk occurring between kidney and the brain. The pathophysiological link of this crosstalk is represented by oxidative stress and inflammatory processes which contribute to the high prevalence of neuropsychiatric disorders, cognitive impairment, and dementia during the natural history of chronic kidney disease. Herein, we provide an overview of the main pathophysiological mechanisms related to high levels of pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and neurotoxins, which play a critical role in the kidney–brain crosstalk. The present paper also explores the respective role of H2S and carnosine in the modulation of oxidative stress and inflammation in the kidney–brain axis. It suggests that these activities are likely mediated, at least in part, via hormetic processes, involving Nrf2 (Nuclear factor-like 2), Hsp 70 (heat shock protein 70), SIRT-1 (Sirtuin-1), Trx (Thioredoxin), and the glutathione system. Metabolic interactions at the kidney and brain axis level operate in controlling and reducing oxidant-induced inflammatory damage and therefore, can be a promising potential therapeutic target to reduce the severity of renal and brain injuries in humans.
Vittorio Calabrese; Maria Scuto; Angela Trovato Salinaro; Giuseppe Dionisio; Sergio Modafferi; Maria Laura Ontario; Valentina Greco; Sebastiano Sciuto; Claus Peter Schmitt; Edward J. Calabrese; Verena Peters. Hydrogen Sulfide and Carnosine: Modulation of Oxidative Stress and Inflammation in Kidney and Brain Axis. Antioxidants 2020, 9, 1303 .
AMA StyleVittorio Calabrese, Maria Scuto, Angela Trovato Salinaro, Giuseppe Dionisio, Sergio Modafferi, Maria Laura Ontario, Valentina Greco, Sebastiano Sciuto, Claus Peter Schmitt, Edward J. Calabrese, Verena Peters. Hydrogen Sulfide and Carnosine: Modulation of Oxidative Stress and Inflammation in Kidney and Brain Axis. Antioxidants. 2020; 9 (12):1303.
Chicago/Turabian StyleVittorio Calabrese; Maria Scuto; Angela Trovato Salinaro; Giuseppe Dionisio; Sergio Modafferi; Maria Laura Ontario; Valentina Greco; Sebastiano Sciuto; Claus Peter Schmitt; Edward J. Calabrese; Verena Peters. 2020. "Hydrogen Sulfide and Carnosine: Modulation of Oxidative Stress and Inflammation in Kidney and Brain Axis." Antioxidants 9, no. 12: 1303.
Long-term clinical outcome of peritoneal dialysis (PD) depends on adequate removal of small solutes and water. The peritoneal endothelium represents the key barrier and peritoneal transport dysfunction is associated with vascular changes. Alanyl-glutamine (AlaGln) has been shown to counteract PD-induced deteriorations but the effect on vascular changes has not yet been elucidated. Using multiplexed proteomic and bioinformatic analyses we investigated the molecular mechanisms of vascular pathology in-vitro (primary human umbilical vein endothelial cells, HUVEC) and ex-vivo (arterioles of patients undergoing PD) following exposure to PD-fluid. An overlap of 1813 proteins (40%) of over 3100 proteins was identified in both sample types. PD-fluid treatment significantly altered 378 in endothelial cells and 192 in arterioles. The HUVEC proteome resembles the arteriolar proteome with expected sample specific differences of mainly immune system processes only present in arterioles and extracellular region proteins primarily found in HUVEC. AlaGln-addition to PD-fluid revealed 359 differentially abundant proteins and restored the molecular process landscape altered by PD fluid. This study provides evidence on validity and inherent limitations of studying endothelial pathomechanisms in-vitro compared to vascular ex-vivo findings. AlaGln could reduce PD-associated vasculopathy by reducing endothelial cellular damage, restoring perturbed abundances of pathologically important proteins and enriching protective processes.
Rebecca Herzog; Maria Bartosova; Silvia Tarantino; Anja Wagner; Markus Unterwurzacher; Juan Manuel Sacnun; Anton M. Lichtenauer; Lilian Kuster; Betti Schaefer; Seth L. Alper; Christoph Aufricht; Claus Peter Schmitt; Klaus Kratochwill. Peritoneal Dialysis Fluid Supplementation with Alanyl-Glutamine Attenuates Conventional Dialysis Fluid-Mediated Endothelial Cell Injury by Restoring Perturbed Cytoprotective Responses. Biomolecules 2020, 10, 1678 .
AMA StyleRebecca Herzog, Maria Bartosova, Silvia Tarantino, Anja Wagner, Markus Unterwurzacher, Juan Manuel Sacnun, Anton M. Lichtenauer, Lilian Kuster, Betti Schaefer, Seth L. Alper, Christoph Aufricht, Claus Peter Schmitt, Klaus Kratochwill. Peritoneal Dialysis Fluid Supplementation with Alanyl-Glutamine Attenuates Conventional Dialysis Fluid-Mediated Endothelial Cell Injury by Restoring Perturbed Cytoprotective Responses. Biomolecules. 2020; 10 (12):1678.
Chicago/Turabian StyleRebecca Herzog; Maria Bartosova; Silvia Tarantino; Anja Wagner; Markus Unterwurzacher; Juan Manuel Sacnun; Anton M. Lichtenauer; Lilian Kuster; Betti Schaefer; Seth L. Alper; Christoph Aufricht; Claus Peter Schmitt; Klaus Kratochwill. 2020. "Peritoneal Dialysis Fluid Supplementation with Alanyl-Glutamine Attenuates Conventional Dialysis Fluid-Mediated Endothelial Cell Injury by Restoring Perturbed Cytoprotective Responses." Biomolecules 10, no. 12: 1678.
Bei schwerer akuter und chronischer Vergiftung durch körpereigene Metabolite oder exogene Substanzen muss bei Kindern eine Blutreinigung (Dialyse) durchgeführt werden. Die meisten der Verfahren können in der Zwischenzeit weitgehend unabhängig vom Alter des Patienten realisiert werden. Bei der Auswahl des Blutreinigungsverfahrens muss auch die zugrunde liegende Erkrankung bzw. die Art der Vergiftung berücksichtigt werden. Wasserlösliche Gifte benötigen grundsätzlich andere Dialyseformen als eiweißgebundene Substanzen.
Claus Peter Schmitt. Dialyse. Psychiatrie und Psychotherapie des Kindes- und Jugendalters 2020, 2407 -2411.
AMA StyleClaus Peter Schmitt. Dialyse. Psychiatrie und Psychotherapie des Kindes- und Jugendalters. 2020; ():2407-2411.
Chicago/Turabian StyleClaus Peter Schmitt. 2020. "Dialyse." Psychiatrie und Psychotherapie des Kindes- und Jugendalters , no. : 2407-2411.
Peritoneal dialysis (PD) is limited by glucose-mediated peritoneal membrane (PM) fibrosis, angiogenesis, and ultrafiltration failure. Influencing PM integrity by pharmacologically targeting sodium-dependent glucose transporter (SGLT)-mediated glucose uptake has not been studied. In this study, wildtype C57Bl/6N mice were treated with high-glucose dialysate via an intraperitoneal catheter, with or without addition of selective SGLT2 inhibitor dapagliflozin. PM structural changes, ultrafiltration capacity, and peritoneal equilibration testing (PET) status for glucose, urea, and creatinine were analyzed. Expression of SGLT and facilitative glucose transporters (GLUT) was analyzed by real-time PCR, immunofluorescence, and immunohistochemistry. Peritoneal effluents were analyzed for cellular and cytokine composition. We found that peritoneal SGLT2 was expressed in mesothelial cells and in skeletal muscle. Dapagliflozin significantly reduced effluent transforming growth factor (TGF-β) concentrations, peritoneal thickening, and fibrosis, as well as microvessel density, resulting in improved ultrafiltration, despite the fact that it did not affect development of high-glucose transporter status. In vitro, dapagliflozin reduced monocyte chemoattractant protein-1 release under high-glucose conditions in human and murine peritoneal mesothelial cells. Proinflammatory cytokine release in macrophages was reduced only when cultured in high-glucose conditions with an additional inflammatory stimulus. In summary, dapagliflozin improved structural and functional peritoneal health in the context of high-glucose PD.
Michael S. Balzer; Song Rong; Johannes Nordlohne; Jan D. Zemtsovski; Sonja Schmidt; Britta Stapel; Maria Bartosova; Sibylle Von Vietinghoff; Hermann Haller; Claus P. Schmitt; Nelli Shushakova. SGLT2 Inhibition by Intraperitoneal Dapagliflozin Mitigates Peritoneal Fibrosis and Ultrafiltration Failure in a Mouse Model of Chronic Peritoneal Exposure to High-Glucose Dialysate. Biomolecules 2020, 10, 1573 .
AMA StyleMichael S. Balzer, Song Rong, Johannes Nordlohne, Jan D. Zemtsovski, Sonja Schmidt, Britta Stapel, Maria Bartosova, Sibylle Von Vietinghoff, Hermann Haller, Claus P. Schmitt, Nelli Shushakova. SGLT2 Inhibition by Intraperitoneal Dapagliflozin Mitigates Peritoneal Fibrosis and Ultrafiltration Failure in a Mouse Model of Chronic Peritoneal Exposure to High-Glucose Dialysate. Biomolecules. 2020; 10 (11):1573.
Chicago/Turabian StyleMichael S. Balzer; Song Rong; Johannes Nordlohne; Jan D. Zemtsovski; Sonja Schmidt; Britta Stapel; Maria Bartosova; Sibylle Von Vietinghoff; Hermann Haller; Claus P. Schmitt; Nelli Shushakova. 2020. "SGLT2 Inhibition by Intraperitoneal Dapagliflozin Mitigates Peritoneal Fibrosis and Ultrafiltration Failure in a Mouse Model of Chronic Peritoneal Exposure to High-Glucose Dialysate." Biomolecules 10, no. 11: 1573.
Peritoneal dialysis (PD) is limited by glucose-mediated peritoneal membrane (PM) fibrosis, angiogenesis and ultrafiltration failure. Influencing PM integrity by pharmacologically targeting sodium-dependent glucose transporter (SGLT)-mediated glucose uptake has not been studied. In this study wildtype C57Bl/6N mice were treated with high-glucose dialysate via an intraperitoneal catheter, with or without addition of selective SGLT2 inhibitor dapagliflozin. PM structural changes, ultrafiltration capacity and PET status for glucose, urea and creatinine were analyzed. Expression of SGLT and GLUT was analyzed by real-time PCR, immunofluorescence and immunohistochemistry. Peritoneal effluents were analyzed for cellular and cytokine composition. We found that peritoneal SGLT2 was expressed in mesothelial cells and in skeletal muscle. Dapagliflozin significantly reduced effluent TGF-β concentrations, peritoneal thickening and fibrosis as well as microvessel density, resulting in improved ultrafiltration, despite the fact that it did not affect development of high glucose transporter status. In vitro, dapagliflozin reduced monocyte chemoattractant protein-1 release under high glucose conditions in human and murine peritoneal mesothelial cells. Pro-inflammatory cytokine release in macrophages was reduced only when cultured in high glucose conditions with an additional inflammatory stimulus. In summary, dapagliflozin improved structural and functional peritoneal health in the context of high glucose PD.
Michael S. Balzer; Song Rong; Johannes Nordlohne; Jan D. Zemtsovski; Sonja Schmidt; Britta Stapel; Maria Bartosova; Sibylle Von Vietinghoff; Hermann Haller; Claus P. Schmitt; Nelli Shushakova. SGLT2 inhibition by intraperitoneal dapagliflozin mitigates peritoneal fibrosis and ultrafiltration failure in a mouse model of chronic peritoneal exposure to high-glucose dialysate. 2020, 1 .
AMA StyleMichael S. Balzer, Song Rong, Johannes Nordlohne, Jan D. Zemtsovski, Sonja Schmidt, Britta Stapel, Maria Bartosova, Sibylle Von Vietinghoff, Hermann Haller, Claus P. Schmitt, Nelli Shushakova. SGLT2 inhibition by intraperitoneal dapagliflozin mitigates peritoneal fibrosis and ultrafiltration failure in a mouse model of chronic peritoneal exposure to high-glucose dialysate. . 2020; ():1.
Chicago/Turabian StyleMichael S. Balzer; Song Rong; Johannes Nordlohne; Jan D. Zemtsovski; Sonja Schmidt; Britta Stapel; Maria Bartosova; Sibylle Von Vietinghoff; Hermann Haller; Claus P. Schmitt; Nelli Shushakova. 2020. "SGLT2 inhibition by intraperitoneal dapagliflozin mitigates peritoneal fibrosis and ultrafiltration failure in a mouse model of chronic peritoneal exposure to high-glucose dialysate." , no. : 1.
Understanding and targeting the molecular basis of peritoneal solute and protein transport is essential to improve peritoneal dialysis (PD) efficacy and patient outcome. Supplementation of PD fluids (PDF) with alanyl-glutamine (AlaGln) increased small solute transport and reduced peritoneal protein loss in a recent clinical trial. Transepithelial resistance and 10 kDa and 70 kDa dextran transport were measured in primary human endothelial cells (HUVEC) exposed to conventional acidic, glucose degradation products (GDP) containing PDF (CPDF) and to low GDP containing PDF (LPDF) with and without AlaGln. Zonula occludens-1 (ZO-1) and claudin-5 were quantified by Western blot and immunofluorescence and in mice exposed to saline and CPDF for 7 weeks by digital imaging analyses. Spatial clustering of ZO-1 molecules was assessed by single molecule localization microscopy. AlaGln increased transepithelial resistance, and in CPDF exposed HUVEC decreased dextran transport rates and preserved claudin-5 and ZO-1 abundance. Endothelial clustering of membrane bound ZO-1 was higher in CPDF supplemented with AlaGln. In mice, arteriolar endothelial claudin-5 was reduced in CPDF, but restored with AlaGln, while mesothelial claudin-5 abundance was unchanged. AlaGln supplementation seals the peritoneal endothelial barrier, and when supplemented to conventional PD fluid increases claudin-5 and ZO-1 abundance and clustering of ZO-1 in the endothelial cell membrane.
Maria Bartosova; Rebecca Herzog; David Ridinger; Eszter Levai; Hanna Jenei; Conghui Zhang; Guadalupe T. González Mateo; Iva Marinovic; Thilo Hackert; Felix Bestvater; Michael Hausmann; Manuel López Cabrera; Klaus Kratochwill; Sotirios G. Zarogiannis; Claus Peter Schmitt. Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid. Biomolecules 2020, 10, 1178 .
AMA StyleMaria Bartosova, Rebecca Herzog, David Ridinger, Eszter Levai, Hanna Jenei, Conghui Zhang, Guadalupe T. González Mateo, Iva Marinovic, Thilo Hackert, Felix Bestvater, Michael Hausmann, Manuel López Cabrera, Klaus Kratochwill, Sotirios G. Zarogiannis, Claus Peter Schmitt. Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid. Biomolecules. 2020; 10 (8):1178.
Chicago/Turabian StyleMaria Bartosova; Rebecca Herzog; David Ridinger; Eszter Levai; Hanna Jenei; Conghui Zhang; Guadalupe T. González Mateo; Iva Marinovic; Thilo Hackert; Felix Bestvater; Michael Hausmann; Manuel López Cabrera; Klaus Kratochwill; Sotirios G. Zarogiannis; Claus Peter Schmitt. 2020. "Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid." Biomolecules 10, no. 8: 1178.
Carnosinase 1 (CN1) is encoded by the Cndp1 gene and degrades carnosine and anserine, two natural histidine-containing dipeptides. In vitro and in vivo studies suggest carnosine- and anserine-mediated protection against long-term sequelae of reactive metabolites accumulating, e.g., in diabetes mellitus. We have characterized the metabolic impact of CN1 in 11- and 55-week-old Cndp1-knockout (Cndp1-KO) mice and litter-matched wildtypes (WT). In Cndp1-KO mice, renal carnosine and anserine concentrations were gender-specifically increased 2- to 9-fold, respectively in the kidney and both most abundant in the renal cortex, but remained unchanged in all other organs and in serum. Renal oxidized/reduced glutathione concentrations, renal morphology and function were unaltered. In Cndp1-KO mice at week 11, renal asparagine, serine and glutamine levels and at week 55, renal arginine concentration were reduced. Renal heat-shock-protein 70 (Hspa1a/b) mRNA declined with age in WT but not in Cndp1-KO mice, transcription factor heat-shock-factor 1 was higher in 55-week-old KO mice. Fasting blood glucose concentrations decreased with age in WT mice, but were unchanged in Cndp1-KO mice. Blood glucose response to intraperitoneal insulin was gender- but not genotype-dependent, the response to intraperitoneal glucose injection was similar in all groups. A global Cndp1-KO selectively, age- and gender-specifically, increases renal carnosine and anserine concentrations, alters renal amino acid- and HSP70 profile and modifies systemic glucose homeostasis. Increase of the natural occurring carnosine and anserine levels in the kidney by modulation of CN1 represents a promising therapeutic approach to mitigate or prevent chronic kidney diseases such as diabetic nephropathy.
Tim Weigand; Florian Colbatzky; Tilman Pfeffer; Sven F. Garbade; Kristina Klingbeil; Florian Colbatzky; Michael Becker; Johanna Zemva; Ruben Bulkescher; Robin Schürfeld; Christian Thiel; Nadine Volk; David Reuss; Georg F. Hoffmann; Marc Freichel; Markus Hecker; Tanja Poth; Thomas Fleming; Gernot Poschet; Claus P. Schmitt; Verena Peters. A Global Cndp1-Knock-Out Selectively Increases Renal Carnosine and Anserine Concentrations in an Age- and Gender-Specific Manner in Mice. International Journal of Molecular Sciences 2020, 21, 4887 .
AMA StyleTim Weigand, Florian Colbatzky, Tilman Pfeffer, Sven F. Garbade, Kristina Klingbeil, Florian Colbatzky, Michael Becker, Johanna Zemva, Ruben Bulkescher, Robin Schürfeld, Christian Thiel, Nadine Volk, David Reuss, Georg F. Hoffmann, Marc Freichel, Markus Hecker, Tanja Poth, Thomas Fleming, Gernot Poschet, Claus P. Schmitt, Verena Peters. A Global Cndp1-Knock-Out Selectively Increases Renal Carnosine and Anserine Concentrations in an Age- and Gender-Specific Manner in Mice. International Journal of Molecular Sciences. 2020; 21 (14):4887.
Chicago/Turabian StyleTim Weigand; Florian Colbatzky; Tilman Pfeffer; Sven F. Garbade; Kristina Klingbeil; Florian Colbatzky; Michael Becker; Johanna Zemva; Ruben Bulkescher; Robin Schürfeld; Christian Thiel; Nadine Volk; David Reuss; Georg F. Hoffmann; Marc Freichel; Markus Hecker; Tanja Poth; Thomas Fleming; Gernot Poschet; Claus P. Schmitt; Verena Peters. 2020. "A Global Cndp1-Knock-Out Selectively Increases Renal Carnosine and Anserine Concentrations in an Age- and Gender-Specific Manner in Mice." International Journal of Molecular Sciences 21, no. 14: 4887.
Carnosine improves diabetic complications, including diabetic nephropathy, in in vivo models. To further understand the underlying mechanism of nephroprotection, we studied the effect of carnosine under glucose-induced stress on cellular stress response proteins in murine immortalized podocytes, essential for glomerular function. High-glucose stress initiated stress response by increasing intracellular heat shock protein 70 (Hsp70), sirtuin-1 (Sirt-1), thioredoxin (Trx), glutamate-cysteine ligase (gamma-glutamyl cysteine synthetase; γ-GCS) and heme oxygenase-1 (HO-1) in podocytes by 30–50% compared to untreated cells. Carnosine (1 mM) also induced a corresponding upregulation of these intracellular stress markers, which was even more prominent compared to glucose for Hsp70 (21%), γ-GCS and HO-1 (13% and 20%, respectively; all p < 0.001). Co-incubation of carnosine (1 mM) and glucose (25 mM) induced further upregulation of Hsp70 (84%), Sirt-1 (52%), Trx (35%), γ-GCS (90%) and HO-1 (73%) concentrations compared to untreated cells (all p < 0.001). The glucose-induced increase in 4-hydroxy-trans-2-nonenal (HNE) and protein carbonylation was reduced dose-dependently by carnosine by more than 50% (p < 0.001). Although podocytes tolerated high carnosine concentrations (10 mM), high carnosine levels only slightly increased Trx and γ-GCS (10% and 19%, respectively, compared to controls; p < 0.001), but not Hsp70, Sirt-1 and HO-1 proteins (p not significant), and did not modify the glucose-induced oxidative stress response. In podocytes, carnosine induced cellular stress tolerance and resilience pathways and was highly effective in reducing high-glucose-induced glycative and lipoperoxidative stress. Carnosine in moderate concentrations exerted a direct podocyte molecular protective action.
Maria Scuto; Angela Trovato Trovato Salinaro; Sergio Modafferi; Alessandra Polimeni; Tilman Pfeffer; Tim Weigand; Vittorio Calabrese; Claus Peter Schmitt; Verena Peters. Carnosine Activates Cellular Stress Response in Podocytes and Reduces Glycative and Lipoperoxidative Stress. Biomedicines 2020, 8, 177 .
AMA StyleMaria Scuto, Angela Trovato Trovato Salinaro, Sergio Modafferi, Alessandra Polimeni, Tilman Pfeffer, Tim Weigand, Vittorio Calabrese, Claus Peter Schmitt, Verena Peters. Carnosine Activates Cellular Stress Response in Podocytes and Reduces Glycative and Lipoperoxidative Stress. Biomedicines. 2020; 8 (6):177.
Chicago/Turabian StyleMaria Scuto; Angela Trovato Trovato Salinaro; Sergio Modafferi; Alessandra Polimeni; Tilman Pfeffer; Tim Weigand; Vittorio Calabrese; Claus Peter Schmitt; Verena Peters. 2020. "Carnosine Activates Cellular Stress Response in Podocytes and Reduces Glycative and Lipoperoxidative Stress." Biomedicines 8, no. 6: 177.
Encapsulating peritoneal sclerosis (EPS) is a life-threatening complication of long-term peritoneal dialysis (PD), which may even occur after patients have switched to hemodialysis (HD) or undergone kidney transplantation. The incidence of EPS varies across the globe and increases with PD vintage. Causative factors are the chronic exposure to bioincompatible PD solutions, which cause long-term modifications of the peritoneum, a high peritoneal transporter status involving high glucose concentrations, peritonitis episodes, and smoldering peritoneal inflammation. Additional potential causes are predisposing genetic factors and some medications. Clinical symptoms comprise signs of intestinal obstruction and a high peritoneal transporter status with incipient ultrafiltration failure. In radiological, macro-, and microscopic studies, a massively fibrotic and calcified peritoneum enclosed the intestine and parietal wall in such cases. Empirical treatments commonly used are corticosteroids and tamoxifen, which has fibrinolytic properties. Immunosuppressants like azathioprine, mycophenolate mofetil, or mTOR inhibitors may also help with reducing inflammation, fibrin deposition, and collagen synthesis and maturation. In animal studies, N-acetylcysteine, colchicine, rosiglitazone, thalidomide, and renin-angiotensin system (RAS) inhibitors yielded promising results. Surgical treatment has mainly been performed in severe cases of intestinal obstruction, with varying results. Mortality rates are still 25–55% in adults and about 14% in children. To reduce the incidence of EPS and improve the outcome of this devastating complication of chronic PD, vigorous consideration of the risk factors, early diagnosis, and timely discontinuation of PD and therapeutic interventions are mandatory, even though these are merely based on empirical evidence.
Rajesh M. Jagirdar; Andreas Bozikas; Sotirios G. Zarogiannis; Maria Bartosova; Claus Peter Schmitt; Vassilios Liakopoulos. Encapsulating Peritoneal Sclerosis: Pathophysiology and Current Treatment Options. International Journal of Molecular Sciences 2019, 20, 5765 .
AMA StyleRajesh M. Jagirdar, Andreas Bozikas, Sotirios G. Zarogiannis, Maria Bartosova, Claus Peter Schmitt, Vassilios Liakopoulos. Encapsulating Peritoneal Sclerosis: Pathophysiology and Current Treatment Options. International Journal of Molecular Sciences. 2019; 20 (22):5765.
Chicago/Turabian StyleRajesh M. Jagirdar; Andreas Bozikas; Sotirios G. Zarogiannis; Maria Bartosova; Claus Peter Schmitt; Vassilios Liakopoulos. 2019. "Encapsulating Peritoneal Sclerosis: Pathophysiology and Current Treatment Options." International Journal of Molecular Sciences 20, no. 22: 5765.
Protein-bound uremic toxins (PBUTs) play a role in the multisystem disease that children on hemodialysis (HD) are facing, but little is known about their levels and protein binding (%PB). In this study, we evaluated the levels and %PB of six PBUTs cross-sectionally in a large pediatric HD cohort (n = 170) by comparing these with healthy and non-dialysis chronic kidney disease (CKD) stage 4–5 (n = 24) children. In parallel β2-microglobulin (β2M) and uric acid (UA) were evaluated. We then explored the impact of age and residual kidney function on uremic toxin levels and %PB using analysis of covariance and Spearman correlation coefficients (rs). We found higher levels of β2M, p-cresyl glucuronide (pCG), hippuric acid (HA), indole acetic acid (IAA), and indoxyl sulfate (IxS) in the HD compared to the CKD4–5 group. In the HD group, a positive correlation between age and pCG, HA, IxS, and pCS levels was shown. Residual urine volume was negatively correlated with levels of β2M, pCG, HA, IAA, IxS, and CMPF (rs −0.2 to −0.5). In addition, we found overall lower %PB of PBUTs in HD versus the CKD4–5 group, and showed an age-dependent increase in %PB of IAA, IxS, and pCS. Furhtermore, residual kidney function was overall positively correlated with %PB of PBUTs. In conclusion, residual kidney function and age contribute to PBUT levels and %PB in the pediatric HD population.
Evelien Snauwaert; Els Holvoet; Wim Van Biesen; Ann Raes; Griet Glorieux; Johan Vande Walle; Sanne Roels; Raymond Vanholder; Varvara Askiti; Karolis Azukaitis; Aysun Bayazit; Nur Canpolat; Michel Fischbach; Nathalie Godefroid; Saoussen Krid; Mieczyslaw Litwin; Lukasz Obrycki; Fabio Paglialonga; Bruno Ranchin; Charlotte Samaille; Franz Schaefer; Claus Peter Schmitt; Brankica Spasojevic; Constantinos J. Stefanidis; Maria Van Dyck; Koen Van Hoeck; Laure Collard; Sunny Eloot; Rukshana Shroff. Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population. Toxins 2019, 11, 235 .
AMA StyleEvelien Snauwaert, Els Holvoet, Wim Van Biesen, Ann Raes, Griet Glorieux, Johan Vande Walle, Sanne Roels, Raymond Vanholder, Varvara Askiti, Karolis Azukaitis, Aysun Bayazit, Nur Canpolat, Michel Fischbach, Nathalie Godefroid, Saoussen Krid, Mieczyslaw Litwin, Lukasz Obrycki, Fabio Paglialonga, Bruno Ranchin, Charlotte Samaille, Franz Schaefer, Claus Peter Schmitt, Brankica Spasojevic, Constantinos J. Stefanidis, Maria Van Dyck, Koen Van Hoeck, Laure Collard, Sunny Eloot, Rukshana Shroff. Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population. Toxins. 2019; 11 (4):235.
Chicago/Turabian StyleEvelien Snauwaert; Els Holvoet; Wim Van Biesen; Ann Raes; Griet Glorieux; Johan Vande Walle; Sanne Roels; Raymond Vanholder; Varvara Askiti; Karolis Azukaitis; Aysun Bayazit; Nur Canpolat; Michel Fischbach; Nathalie Godefroid; Saoussen Krid; Mieczyslaw Litwin; Lukasz Obrycki; Fabio Paglialonga; Bruno Ranchin; Charlotte Samaille; Franz Schaefer; Claus Peter Schmitt; Brankica Spasojevic; Constantinos J. Stefanidis; Maria Van Dyck; Koen Van Hoeck; Laure Collard; Sunny Eloot; Rukshana Shroff. 2019. "Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population." Toxins 11, no. 4: 235.
Peritoneal dialysis (PD) is a cost-effective, home-based therapy for patients with end-stage renal disease achieving similar outcome as compared to hemodialysis. Still, a minority of patients only receive PD. To a significant extend, this discrepancy is explained by major limitations regarding PD efficiency and sustainability. Due to highly unphysiological composition of PD fluids, the peritoneal membrane undergoes rapid morphological and long-term functional alterations, which limit the treatment and contribute to adverse patient outcome. This review is focused on the peritoneal membrane ultrastructure and its transformation in patients with kidney disease and chronic PD, underlying molecular mechanisms, and potential systemic sequelae. Current knowledge on the impact of conventional and second-generation PD fluids is described; novel strategies and innovative PD fluid types are discussed.
Maria Bartosova; Claus Peter Schmitt. Biocompatible Peritoneal Dialysis: The Target Is Still Way Off. Frontiers in Physiology 2019, 9, 1 .
AMA StyleMaria Bartosova, Claus Peter Schmitt. Biocompatible Peritoneal Dialysis: The Target Is Still Way Off. Frontiers in Physiology. 2019; 9 ():1.
Chicago/Turabian StyleMaria Bartosova; Claus Peter Schmitt. 2019. "Biocompatible Peritoneal Dialysis: The Target Is Still Way Off." Frontiers in Physiology 9, no. : 1.
Bei schwerer akuter und chronischer Vergiftung durch körpereigene Metabolite oder exogene Substanzen muss bei Kindern eine Blutreinigung (Dialyse) durchgeführt werden. Die meisten der Verfahren können in der Zwischenzeit weitgehend unabhängig vom Alter des Patienten realisiert werden. Bei der Auswahl des Blutreinigungsverfahrens muss auch die zugrunde liegende Erkrankung bzw. die Art der Vergiftung berücksichtigt werden. Wasserlösliche Gifte benötigen grundsätzlich andere Dialyseformen als eiweißgebundene Substanzen.
Claus Peter Schmitt. Dialyse bei Kindern und Jugendlichen. Psychiatrie und Psychotherapie des Kindes- und Jugendalters 2018, 1 -5.
AMA StyleClaus Peter Schmitt. Dialyse bei Kindern und Jugendlichen. Psychiatrie und Psychotherapie des Kindes- und Jugendalters. 2018; ():1-5.
Chicago/Turabian StyleClaus Peter Schmitt. 2018. "Dialyse bei Kindern und Jugendlichen." Psychiatrie und Psychotherapie des Kindes- und Jugendalters , no. : 1-5.
Background/Aims: In rodents, carnosine treatment improves diabetic nephropathy, whereas little is known about the role and function of anserine, the methylated form of carnosine. Methods: Antioxidant activity was measured by oxygen radical absorbance capacity and oxygen stress response in human renal tubular cells (HK-2) by RT-PCR and Western-Immunoblotting. In wildtype (WT) and diabetic mice (db/db), the effect of short-term anserine treatment on blood glucose, proteinuria and vascular permeability was measured. Results: Anserine has a higher antioxidant capacity compared to carnosine (p < 0.001). In tubular cells (HK-2) stressed with 25 mM glucose or 20–100 µM hydrogen peroxide, anserine but not carnosine, increased intracellular heat shock protein (Hsp70) mRNA and protein levels. In HK-2 cells stressed with glucose, co-incubation with anserine also increased hemeoxygenase (HO-1) protein and reduced total protein carbonylation, but had no effect on cellular sirtuin-1 and thioredoxin protein concentrations. Three intravenous anserine injections every 48 h in 12-week-old db/db mice, improved blood glucose by one fifth, vascular permeability by one third, and halved proteinuria (all p < 0.05). Conclusion: Anserine is a potent antioxidant and activates the intracellular Hsp70/HO-1 defense system under oxidative and glycative stress. Short-term anserine treatment in diabetic mice improves glucose homeostasis and nephropathy.
Verena Peters; Vittorio Calabrese; Elisabete Forsberg; Nadine Volk; Thomas Fleming; Hans Baelde; Tim Weigand; Christian Thiel; Angela Trovato; Maria Scuto; Sergio Modafferi; Claus Peter Schmitt. Protective Actions of Anserine Under Diabetic Conditions. International Journal of Molecular Sciences 2018, 19, 2751 .
AMA StyleVerena Peters, Vittorio Calabrese, Elisabete Forsberg, Nadine Volk, Thomas Fleming, Hans Baelde, Tim Weigand, Christian Thiel, Angela Trovato, Maria Scuto, Sergio Modafferi, Claus Peter Schmitt. Protective Actions of Anserine Under Diabetic Conditions. International Journal of Molecular Sciences. 2018; 19 (9):2751.
Chicago/Turabian StyleVerena Peters; Vittorio Calabrese; Elisabete Forsberg; Nadine Volk; Thomas Fleming; Hans Baelde; Tim Weigand; Christian Thiel; Angela Trovato; Maria Scuto; Sergio Modafferi; Claus Peter Schmitt. 2018. "Protective Actions of Anserine Under Diabetic Conditions." International Journal of Molecular Sciences 19, no. 9: 2751.
Background Management of children with congenital nephrotic syndrome (CNS) is challenging. Bilateral nephrectomies followed by dialysis and transplantation are practiced in most centres, but conservative treatment may also be effective. Methods We conducted a 6-year review across members of the European Society for Paediatric Nephrology Dialysis Working Group to compare management strategies and their outcomes in children with CNS. Results Eighty children (50% male) across 17 tertiary nephrology units in Europe were included (mutations in NPHS1, n = 55; NPHS2, n = 1; WT1, n = 9; others, n = 15). Excluding patients with mutations in WT1, antiproteinuric treatment was given in 42 (59%) with an increase in S-albumin in 70% by median 6 (interquartile range: 3–8) g/L (P < 0.001). Following unilateral nephrectomy, S-albumin increased by 4 (1–8) g/L (P = 0.03) with a reduction in albumin infusion dose by 5 (2–9) g/kg/week (P = 0.02). Median age at bilateral nephrectomies (n = 29) was 9 (7–16) months. Outcomes were compared between two groups of NPHS1 patients: those who underwent bilateral nephrectomies (n = 25) versus those on conservative management (n = 17). The number of septic or thrombotic episodes and growth were comparable between the groups. The response to antiproteinuric treatment, as well as renal and patient survival, was independent of NPHS1 mutation type. At final follow-up (median age 34 months) 20 (80%) children in the nephrectomy group were transplanted and 1 died. In the conservative group, 9 (53%) remained without dialysis, 4 (24%; P < 0.001) were transplanted and 2 died. Conclusion An individualized, stepwise approach with prolonged conservative management may be a reasonable alternative to early bilateral nephrectomies and dialysis in children with CNS and NPHS1 mutations. Further prospective studies are needed to define indications for unilateral nephrectomy.
Stephanie Dufek; Tuula Holtta; Agnes Trautmann; Elisa Ylinen; Harika Alpay; Gema Ariceta; Christoph Aufricht; Justine Bacchetta; Sevcan A Bakkaloglu; Aysun Bayazit; Rumeysa Yasemin Cicek; Ismail Dursun; Ali Düzova; Mesiha Ekim; Daniela Iancu; Augustina Jankauskiene; Günter Klaus; Fabio Paglialonga; Andrea Pasini; Nikoleta Printza; Valerie Said Conti; Maria Do Sameiro Faria; Claus Peter Schmitt; Constantinos J Stefanidis; Enrico Verrina; Enrico Vidal; Karel Vondrak; Hazel Webb; Argyroula Zampetoglou; Detlef Bockenhauer; Alberto Edefonti; Rukshana Shroff. Management of children with congenital nephrotic syndrome: challenging treatment paradigms. Nephrology Dialysis Transplantation 2018, 34, 1369 -1377.
AMA StyleStephanie Dufek, Tuula Holtta, Agnes Trautmann, Elisa Ylinen, Harika Alpay, Gema Ariceta, Christoph Aufricht, Justine Bacchetta, Sevcan A Bakkaloglu, Aysun Bayazit, Rumeysa Yasemin Cicek, Ismail Dursun, Ali Düzova, Mesiha Ekim, Daniela Iancu, Augustina Jankauskiene, Günter Klaus, Fabio Paglialonga, Andrea Pasini, Nikoleta Printza, Valerie Said Conti, Maria Do Sameiro Faria, Claus Peter Schmitt, Constantinos J Stefanidis, Enrico Verrina, Enrico Vidal, Karel Vondrak, Hazel Webb, Argyroula Zampetoglou, Detlef Bockenhauer, Alberto Edefonti, Rukshana Shroff. Management of children with congenital nephrotic syndrome: challenging treatment paradigms. Nephrology Dialysis Transplantation. 2018; 34 (8):1369-1377.
Chicago/Turabian StyleStephanie Dufek; Tuula Holtta; Agnes Trautmann; Elisa Ylinen; Harika Alpay; Gema Ariceta; Christoph Aufricht; Justine Bacchetta; Sevcan A Bakkaloglu; Aysun Bayazit; Rumeysa Yasemin Cicek; Ismail Dursun; Ali Düzova; Mesiha Ekim; Daniela Iancu; Augustina Jankauskiene; Günter Klaus; Fabio Paglialonga; Andrea Pasini; Nikoleta Printza; Valerie Said Conti; Maria Do Sameiro Faria; Claus Peter Schmitt; Constantinos J Stefanidis; Enrico Verrina; Enrico Vidal; Karel Vondrak; Hazel Webb; Argyroula Zampetoglou; Detlef Bockenhauer; Alberto Edefonti; Rukshana Shroff. 2018. "Management of children with congenital nephrotic syndrome: challenging treatment paradigms." Nephrology Dialysis Transplantation 34, no. 8: 1369-1377.
In patients with chronic kidney disease (CKD), renal synthesis of active vitamin D [1,25-dihydroxyvitamin D (1,25(OH)2D)] declines and is associated with hypocalcaemia, secondary hyperparathyroidism and the spectrum of CKD–mineral and bone disorder (MBD). In advanced CKD, active vitamin D analogues, including alfacalcidol, calcitriol and paricalcitol, are routinely administered. There are few studies on the use of vitamin D analogues in children with CKD and on dialysis. It is difficult to define bone-specific outcomes that can guide treatment with active vitamin D analogues in children with CKD-MBD. A core working group (WG) of the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis WGs has developed recommendations for the use of active vitamin D therapy in children with CKD and on dialysis. A second document in parallel with this one covers treatment recommendations for native vitamin D therapy. The WGs have performed an extensive literature review to include systematic reviews and randomized controlled trials in adults and children with CKD and prospective observational studies in children with CKD. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system was used to develop and grade the recommendations. In the absence of applicable study data, the opinion of experts from the ESPN CKD-MBD and Dialysis WGs is provided, but clearly GRADE-ed as such and must be carefully considered by the treating physician and adapted to individual patient needs as appropriate.
Rukshana Shroff; Mandy Wan; Evi V. Nagler; Sevcan Bakkaloğlu; Mario Cozzolino; Justine Bacchetta; Alberto Edefonti; Constantinos J. Stefanidis; Johan Vande Walle; Gema Ariceta; Günter Klaus; Dieter Haffner; Claus Peter Schmitt; On Behalf Of The European Society For Paediatric Nephrology Chronic Kidney Disease Mineral And Bone Disorders And Dialysis Working Groups. Clinical practice recommendations for treatment with active vitamin D analogues in children with chronic kidney disease Stages 2–5 and on dialysis. Nephrology Dialysis Transplantation 2017, 32, 1114 -1127.
AMA StyleRukshana Shroff, Mandy Wan, Evi V. Nagler, Sevcan Bakkaloğlu, Mario Cozzolino, Justine Bacchetta, Alberto Edefonti, Constantinos J. Stefanidis, Johan Vande Walle, Gema Ariceta, Günter Klaus, Dieter Haffner, Claus Peter Schmitt, On Behalf Of The European Society For Paediatric Nephrology Chronic Kidney Disease Mineral And Bone Disorders And Dialysis Working Groups. Clinical practice recommendations for treatment with active vitamin D analogues in children with chronic kidney disease Stages 2–5 and on dialysis. Nephrology Dialysis Transplantation. 2017; 32 (7):1114-1127.
Chicago/Turabian StyleRukshana Shroff; Mandy Wan; Evi V. Nagler; Sevcan Bakkaloğlu; Mario Cozzolino; Justine Bacchetta; Alberto Edefonti; Constantinos J. Stefanidis; Johan Vande Walle; Gema Ariceta; Günter Klaus; Dieter Haffner; Claus Peter Schmitt; On Behalf Of The European Society For Paediatric Nephrology Chronic Kidney Disease Mineral And Bone Disorders And Dialysis Working Groups. 2017. "Clinical practice recommendations for treatment with active vitamin D analogues in children with chronic kidney disease Stages 2–5 and on dialysis." Nephrology Dialysis Transplantation 32, no. 7: 1114-1127.
Klaus Kratochwill; Silvia Tarantino; Anton Lichtenauer; Christoph Aufricht; Rebecca Herzog; Maria Bartosova; Claus Peter Schmitt. MO059ALANYLGLUTAMINE ATTENUATES CELLULAR INJURY AND ENHANCES CYTOPROTECTIVE RESPONSES IN ENDOTHELIAL CELLS FOLLOWING EXPOSURE TO PERITONEAL DIALYSIS FLUIDS. Nephrology Dialysis Transplantation 2017, 32, 1 .
AMA StyleKlaus Kratochwill, Silvia Tarantino, Anton Lichtenauer, Christoph Aufricht, Rebecca Herzog, Maria Bartosova, Claus Peter Schmitt. MO059ALANYLGLUTAMINE ATTENUATES CELLULAR INJURY AND ENHANCES CYTOPROTECTIVE RESPONSES IN ENDOTHELIAL CELLS FOLLOWING EXPOSURE TO PERITONEAL DIALYSIS FLUIDS. Nephrology Dialysis Transplantation. 2017; 32 (suppl_3):1.
Chicago/Turabian StyleKlaus Kratochwill; Silvia Tarantino; Anton Lichtenauer; Christoph Aufricht; Rebecca Herzog; Maria Bartosova; Claus Peter Schmitt. 2017. "MO059ALANYLGLUTAMINE ATTENUATES CELLULAR INJURY AND ENHANCES CYTOPROTECTIVE RESPONSES IN ENDOTHELIAL CELLS FOLLOWING EXPOSURE TO PERITONEAL DIALYSIS FLUIDS." Nephrology Dialysis Transplantation 32, no. suppl_3: 1.
The risk of developing type II diabetic nephropathy (DN) is lower in patients carrying theTo evaluate the impact of theRenal failure progression was independent ofOur findings in pediatric CKD patients suggest that the nephroprotective effect of the
Verena Peters; Moustafa Kebbewar; Bart Janssen; Georg F. Hoffmann; Kristina Möller; Simone Wygoda; Marina Charbit; Ana Fernandes-Teixeira; Nikola Jeck; Johannes Zschocke; Claus Peter Schmitt; Franz Schäfer; Elke Wühl; for the ESCAPE Trial Group. CNDP1 genotype and renal survival in pediatric nephropathies. Journal of Pediatric Endocrinology and Metabolism 2016, 29, 1 .
AMA StyleVerena Peters, Moustafa Kebbewar, Bart Janssen, Georg F. Hoffmann, Kristina Möller, Simone Wygoda, Marina Charbit, Ana Fernandes-Teixeira, Nikola Jeck, Johannes Zschocke, Claus Peter Schmitt, Franz Schäfer, Elke Wühl, for the ESCAPE Trial Group. CNDP1 genotype and renal survival in pediatric nephropathies. Journal of Pediatric Endocrinology and Metabolism. 2016; 29 (7):1.
Chicago/Turabian StyleVerena Peters; Moustafa Kebbewar; Bart Janssen; Georg F. Hoffmann; Kristina Möller; Simone Wygoda; Marina Charbit; Ana Fernandes-Teixeira; Nikola Jeck; Johannes Zschocke; Claus Peter Schmitt; Franz Schäfer; Elke Wühl; for the ESCAPE Trial Group. 2016. "CNDP1 genotype and renal survival in pediatric nephropathies." Journal of Pediatric Endocrinology and Metabolism 29, no. 7: 1.