Gambro Dialysatoren GmbH

Hechingen, Germany

Gambro Dialysatoren GmbH

Hechingen, Germany
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Ferris H.U.,Max Planck Institute for Developmental Biology | Zeth K.,University of the Basque Country | Hulko M.,Gambro Dialysatoren GmbH | Dunin-Horkawicz S.,International Institute of Molecular and Cell Biology | Lupas A.N.,Max Planck Institute for Developmental Biology
Journal of Structural Biology | Year: 2014

Bacterial chemotaxis receptors are elongated homodimeric coiled-coil bundles, which transduce signals generated in an N-terminal sensor domain across 15-20. nm to a conserved C-terminal signaling subdomain. This signal transduction regulates the activity of associated kinases, altering the behavior of the flagellar motor and hence cell motility. Signaling is in turn modulated by selective methylation and demethylation of specific glutamate and glutamine residues in an adaptation subdomain. We have determined the structure of a chimeric protein, consisting of the HAMP domain from Archaeoglobus fulgidus Af1503 and the methyl-accepting domain of Escherichia coli Tsr. It shows a 21. nm coiled coil that alternates between two coiled-coil packing modes: canonical knobs-into-holes and complementary x-da, a variant form related to the canonical one by axial rotation of the helices. Comparison of the obtained structure to the Thermotoga maritima chemoreceptor TM1143 reveals that they adopt different axial rotation states in their adaptation subdomains. This conformational change is presumably induced by the upstream HAMP domain and may modulate the affinity of the chemoreceptor to the methylation-demethylation system. The presented findings extend the cogwheel model for signal transmission to chemoreceptors. © 2014 The Authors.


Haag-Weber M.,St. Elisabeth Krankenhaus | Kramer R.,KfH Nierenzentrum | Haake R.,KfH Nierenzentrum | Islam M.S.,Center Hospitalier University | And 4 more authors.
Nephrology Dialysis Transplantation | Year: 2010

Background. Residual renal function (RRF) impacts outcome of peritoneal dialysis (PD) patients. Some PD fluids contain glucose degradation products (GDPs) which have been shown to affect cell systems and tissues. They may also act as precursors of advanced glycosylation endproducts (AGEs) both locally and systemically, potentially inflicting damage to the kidney as the major organ for AGE elimination. We conducted a clinical study in PD patients to see if the content of GDP in the PD fluid has any influence on the decline of the residual renal function.Methods. In a multicentre approach, 80 patients (GFF ≥ 3 mL/min/1.732 or creatinine clearance ≥3 mL/min/1.73 m2) were randomized to treatment with a PD fluid containing low levels of GDP or standard PD fluid for 18 months. RRF was assessed every 4-6 weeks. Fluid balance, mesothelial cell mass marker CA125, peritoneal membrane characteristics, C-reactive protein (CRP), total protein, albumin, electrolytes and phosphate were measured repeatedly.Results. Data from 69 patients revealed a significant difference in monthly RRF change:-1.5% (95% CI =-3.07% to +0.03%) with low GDP (43 patients) vs-4.3% (95% CI =-6.8% to-2.06%) with standard fluids (26 patients) (P = 0.0437), independent of angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker medication. Twenty-four-hour urine volume declined more slowly with low-GDP fluid compared to standard fluids (12 vs 38 mL/month, P = 0.0241), and monthly change of phosphate level was smaller (+0.013 vs +0.061 mg/dL, P = 0.0381).Conclusions. Our prospective study demonstrates for the first time a significant benefit concerning preservation of RRF and urine volume of using a PD fluid with low GDP levels. These findings suggest that GDPs might affect patient outcome related to RRF. © The Author 2010.


PubMed | University of Tübingen, Martin Luther University of Halle Wittenberg, Charité - Medical University of Berlin, Gambro Dialysatoren GmbH and NMI Technology Transfer GmbH
Type: Journal Article | Journal: PloS one | Year: 2017

To increase the removal of middle-sized uremic toxins a new membrane with enhanced permeability and selectivity, called Medium Cut-Off membrane (MCO-Ci) has been developed that at the same time ensures the retention of albumin. Because many middle-sized substances may contribute to micro-inflammation we hypothesized that the use of MCO-Ci influences the inflammatory state in hemodialysis patients.The randomized crossover trial in 48 patients compared MCO-Ci dialysis to High-flux dialysis of 4 weeks duration each plus 8 weeks extension phase. Primary endpoint was the gene expression of TNF- and IL-6 in peripheral blood mononuclear cells (PBMCs), secondary endpoints were plasma levels of specified inflammatory mediators and cytokines.After four weeks of MCO-Ci the expression of TNF- mRNA (Relative quantification (RQ) from 0.92 0.34 to 0.75 0.31, -18.5%, p<0.001)- and IL-6 mRNA (RQ from 0.78 0.80 to 0.60 0.43, -23.1%, p<0.01) was reduced to a significantly greater extent than with High-flux dialyzers (TNF mRNA-RQ: -14.3%; IL-6 mRNA-RQ: -3.5%). After retransformation of logarithmically transformed data, measurements after MCO were reduced to 82% of those after HF (95% CI 74%-91%). 4 weeks use of MCO-Ci resulted in long-lasting change in plasma levels of several cytokines and other substances with a significant decrease for sTNFR1, kappa and lambda free light chains, urea and an increase for Lp-PLA2 (PLA2G7) compared to High-flux. Albumin levels dropped significantly after 4 weeks of MCO dialysis but increased after additional 8 weeks of MCO dialysis. Twelve weeks treatment with MCO-Ci was well tolerated regarding the number of (S)AEs. In the extension period levels of CRP, TNF--mRNA and IL-6 mRNA remained stable in High-flux as well as in MCO-Ci.MCO-Ci dialyzers modulate inflammation in chronic HD patients to a greater extent compared to High-flux dialyzers. Transcription of pro-inflammatory cytokines in peripheral leukocytes is markedly reduced and removal of soluble mediators is enhanced with MCO dialysis. Serum albumin concentrations stabilize after an initial drop. These results encourage further trials with longer treatment periods and clinical endpoints.


Sakota R.,Gambro | Lodi C.A.,Gambro | Sconziano S.A.,Gambro | Beck W.,Gambro Dialysatoren GmbH | Bosch J.P.,Gambro
Artificial Organs | Year: 2015

Gradual deterioration of red blood cells (RBCs) due to mechanical stress (chronic hemolysis) is unavoidable during treatments that involve extracorporeal blood circulation, such as hemodialysis (HD). This effect is generally undetectable and does not generate any acute symptoms, but it leads to an increase in plasma free hemoglobin (fHb). There are no absolute safety levels for fHb increase, indicating the need for an empirical evaluation using comparative testing. The increase in fHb levels was investigated in vitro by applying double-needle double-pump HD (HD-DNDP), a new modality in which arterial and venous pumps both run continuously. fHb was measured during typical and worst-case simulated dialysis treatments (double-needle single-pump HD [HD-DNSP], hemodiafiltration [HDF-DN], single-needle double-pump HD [HD-SNDP], and HD-DNDP) performed in vitro using bovine blood for 4 h. Hemolysis-related indices (fHb%; index of hemolysis, IH; and normalized IH) were calculated and used for comparison. The increase in fHb during either HDF-DN or HD-SNDP with Artis and AK200 dialysis machines was similar, while the fHb at the maximum real blood flow rate (Qbreal) at the completion of the HD-DNDP treatment on Artis was higher than that for HD-DNSP using a Phoenix dialysis machine (fHb%=1.24±0.13 and 0.92±0.12 for the Artis machine with HD-DNDP at Qbreal=450mL/min and Phoenix with HD-DNSP at Qbreal=500 mL/min, respectively). However, the fHb levels increased linearly, and no steep changes were observed. The increases observed during HD-DNDP were the same order of magnitude as those for widely used bloodlines and treatment modes for delivering dialysis treatments. The observed results matched literature findings, and thus the measured fHb trends are not predicted to have clinical side effects. HD-DNDP treatment with Artis does not merit any additional concern regarding mechanical stress to RBCs compared with that observed for routinely used dialysis treatments, bloodlines and machines. Although the in vitro measurement of the fHb increase in bovine blood does not allow a prediction of the absolute level of blood mechanical damage or the possible effects in humans, such measurements are valuable for assessing hemolytic harm by performing tests comparing the proposed treatment with existing devices. © 2015 The Authors.


Louis Chakkalakal G.,Helmholtz Center Geesthacht | Alexandre M.,Helmholtz Center Geesthacht | Alexandre M.,University of Liège | Abetz C.,Helmholtz Center Geesthacht | And 3 more authors.
Macromolecular Chemistry and Physics | Year: 2012

The surface of silica nanoparticles is modified using the "grafting from" technique. A multi-step reaction is conducted to modify their surface properties. (3-glycidoxypropyl) trimethoxysilane (GPS) is used as the coupling agent for the fixation of atom transfer radical polymerization (ATRP) initiator. The grafting efficiency of GPS mixed with aqueous suspension of silica nanoparticles is studied, followed by the coupling efficiency towards ATRP initiator. The bromide concentration of ATRP initiator is kept constant for comparative kinetic studies of styrene and MMA polymerizations. The consequences at high conversions and the particle size distribution are studied. The behaviour of the glass transition temperature of either polymer-modified particles and the nature of dispersion of polymer-coated silica particles are analyzed. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Meijers B.,Laboratory of Nephrology | Meijers B.,Catholic University of Leuven | Maas R.J.H.,Radboud University Nijmegen | Sprangers B.,Laboratory of Nephrology | And 16 more authors.
Kidney International | Year: 2014

The soluble urokinase receptor (suPAR) promotes proteinuria and induces focal segmental glomerulosclerosis (FSGS)-like lesions in mice. A serum suPAR concentration cutoff of 3000 pg/ml has been proposed as a clinical biomarker for patients with FSGS. Interestingly, several studies in patients with glomerulopathy found an inverse correlation between the estimated glomerular filtration rate (eGFR) and suPAR. As patients with FSGS present at different eGFRs, we studied the relationship between eGFR and suPAR in a cohort of 476 non-FSGS patients and 54 patients with biopsy-proven idiopathic FSGS. In the non-FSGS patients, eGFR was the strongest significant determinant of suPAR. The proposed cutoff for suPAR in FSGS patients was exceeded in 17%, 39%, and 88% in patients with eGFRs of more than 60, 45-60, and 30-45 ml/min per 1.73 m 2, respectively. In patients with eGFR of <30 ml/min per 1.73 m 2, suPAR exceeded the cutoff in 95% of patients. Levels of suPAR in patients with idiopathic FSGS overlapped with non-FSGS controls and for any given eGFR did not discriminate FSGS cases from non-FSGS controls. In the overall cohort, there was a negative association between idiopathic FSGS and suPAR, and idiopathic FSGS was not an independent predictor of FSGS concentration over 3000 pg/ml. Thus, this study does not support an absolute, eGFR-independent, suPAR concentration cutoff as a biomarker for underlying FSGS pathology and questions the validity of relative, eGFR-dependent suPAR cutoff values. © 2013 International Society of Nephrology.


Dutczak S.M.,MESA Institute for Nanotechnology | Dutczak S.M.,Gambro Dialysatoren GmbH | Cuperus F.P.,SolSep B.V. Robust Membrane Technologies | Wessling M.,MESA Institute for Nanotechnology | And 3 more authors.
Separation and Purification Technology | Year: 2013

We report for the first time successful crosslinking of polyamide-imide (Torlon®) based membranes using di-isocyanates. The crosslinked membranes are resistant to N-methyl pyrrolidone (which is solvent of the non-crosslinked membranes) and have very good mechanical properties. In contrast to the state-of-the-art polyimide crosslinked membranes, the created covalent bond is expected to be thermally stable enabling applications at elevated temperatures. The transport characteristics (permeance and molecular weight cut off - MWCO) of the crosslinked membranes are changed in comparison to non-crosslinked ones. This suggests that the crosslinking process could be used to tailor these characteristics. © 2012 Elsevier B.V. All rights reserved.


Majeed S.,Helmholtz Center Geesthacht | Fierro D.,Helmholtz Center Geesthacht | Fierro D.,Reutlingen University | Buhr K.,Helmholtz Center Geesthacht | And 5 more authors.
Journal of Membrane Science | Year: 2012

Hydroxyl functionalized multi-walled carbon nanotubes (MWCNTs) were blended with polyacrylonitrile (PAN) to prepare ultrafiltration membranes by a phase inversion process. Three different concentrations of MWCNTs were used in PAN, i.e. 0.5, 1 and 2. wt%. The water flux of the membranes increased by 63% at 0.5. wt% loading of MWCNTs compared to neat PAN membranes. The water flux decreased upon further increase in the concentration of MWCNTs, but at 2. wt% loading it was still higher compared to pure PAN membranes. The surface hydrophilicity of the membranes was enhanced upon the addition of MWCNTs, as observed by contact angle measurements. The increased hydrophilicity might have an impact on the improved water flux. All the membranes showed a molecular weight cut off (MWCO) of approximately 50. kg/mol. Surface pore size analysis by scanning electron microscopy (SEM) showed no significant difference in the mean pore size of the nanocomposite membranes compared to the neat membranes. The cross section morphology was influenced by the introduction of MWCNTs where less but enlarged macrovoids were observed, particularly prominent at a loading of 2. wt% MWCNTs. The membranes containing 2. wt% MWCNTs showed 36% improvement in resistance against compaction compared to neat membranes. Furthermore, the tensile strength of the membranes at 2. wt% MWCNTs loading increased over 97% compared to neat ones. © 2012 Elsevier B.V.


Axelsson J.,Lund University | oberg C.M.,Lund University | Rippe A.,Lund University | Krause B.,Gambro Dialysatoren GmbH | Rippe B.,Lund University
Journal of Membrane Science | Year: 2012

The aim of the present study was to investigate the size-selectivity of two different synthetic dialyzing membranes, having widely differing sieving properties, with respect to their handling of polydispersed fluorescein isothiocyanate (FITC)-Ficoll, FITC-dextran and of proteins, i.e. 125I-human serum albumin (RISA) and 125I-myoglobin (Myo). Are Ficoll and dextran, compared to proteins, " hyperpermeable" across synthetic dialyzing membranes, similar to their behavior across the glomerular filtration barrier (GFB)? A high-flux membrane (HF-Revaclear ®; n=12) and a high cut-off membrane (HCO; n=14) in capillary mini-dialyzers were perfused with diluted horse serum. The perfusate contained polydisperse FITC-Ficoll 70/400 or FITC-dextran (molradius 13-80Å), FITC-Inulin, and, in some experiments, RISA/Myo. After a priming period, sampling of filtrate occurred, and a midpoint plasma sample taken. Filtrate-to-plasma concentration ratios (θ) vs. molecular radius (a e) were assessed using HPLC for Ficoll and dextran. Size-selectivity for Ficoll increased in the order: HF-Revaclear ®


Fierro D.,Helmholtz Center Geesthacht | Fierro D.,Reutlingen University | Boschetti-de-Fierro A.,Helmholtz Center Geesthacht | Boschetti-de-Fierro A.,Gambro Dialysatoren GmbH | Abetz V.,Helmholtz Center Geesthacht
Journal of Membrane Science | Year: 2012

The solution-diffusion with imperfections model has been used together with diffusion models such as the Vrentas & Duda diffusion theory and the Wesselingh & Bollen multicomponent diffusion model as a tool to successfully describe the permeation behavior of mixtures of ketones and glycols through polydimethylsiloxane composite membranes in a cross-flow membrane cell for pressures varying from 10 to 40. bar. The model has shown the great importance of an accurate determination of the diffusion coefficients and the average concentration of permeants inside the membrane into the successful modeling of nanofiltration experiments. © 2012 Elsevier B.V.

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