@article{MarzoccoFazeliDiMiccoetal.2018,
  author    = {Marzocco, Stefania and Fazeli, Gholamreza and Di Micco, Lucia and Autore, Giuseppina and Adesso, Simona and Dal Piaz, Fabrizio and Heidland, August and Di Iorio, Biagio},
  title     = {Supplementation of short-chain fatty acid, sodium propionate, in patients on maintenance hemodialysis: beneficial effects on inflammatory parameters and gut-derived uremic toxins, a pilot study (PLAN Study)},
  series = {Journal of Clinical Medicine},
  volume    = {7},
  journal   = {Journal of Clinical Medicine},
  number    = {10},
  issn      = {2077-0383},
  doi       = {10.3390/jcm7100315},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197626},
  pages     = {315},
  year      = {2018},
  abstract  = {Background: In end-stage renal disease (ESRD), gut-derived uremic toxins play a crucial role in the systemic inflammation and oxidative stress promoting the excess morbidity and mortality. The biochemical derangement is in part a consequence of an insufficient generation of short-chain fatty acids (SCFA) due to the dysbiosis of the gut and an insufficient consumption of the fermentable complex carbohydrates. Aim of the study: The primary end-point was to evaluate the potential efficacy of SCFA (specifically, sodium propionate (SP)) for patients on maintenance hemodialysis (MHD) on systemic inflammation. Secondary end-points included potential attenuation of oxidative stress markers, insulin resistance and production of gut-derived uremic toxins indoxyl sulfate and p-cresol sulfate, as well as health status after SP supplementation. Study design: We performed a single-center non-randomized pilot study in 20 MHD patients. They received the food additive SP with a daily intake of 2 × 500 mg in the form of capsules for 12 weeks. Pre-dialysis blood samples were taken at the beginning, after six weeks and at the end of the administration period, as well as four weeks after withdrawal of the treatment. Results: The subjects revealed a significant decline of inflammatory parameters C-reactive protein (-46\%), interleukin IL-2 (-27\%) and IL-17 (-15\%). The inflammatory parameters IL-6 and IFN-gamma showed a mild non-significant reduction and the anti-inflammatory cytokine IL-10 increased significantly (+71\%). While the concentration of bacterial endotoxins and TNF-α remained unchanged, the gut-derived uremic toxins, indoxyl sulfate (-30\%) and p-cresyl sulfate (-50\%), revealed a significant decline. The SP supplementation reduced the parameters of oxidative stress malondialdehyde (-32\%) and glutathione peroxidase activity (-28\%). The serum insulin levels dropped by 30\% and the HOMA-index by 32\%. The reduction of inflammatory parameters was associated with a lowering of ferritin and a significant increase in transferrin saturation (TSAT). Four weeks after the end of the treatment phase, all improved parameters deteriorated again. Evaluation of the psycho-physical performance with the short form 36 (SF-36) questionnaire showed an enhancement in the self-reported physical functioning, general health, vitality and mental health. The SP supplementation was well tolerated and without important side effects. No patient had left the study due to intolerance to the medication. The SP supplementation in MHD patients reduced pro-inflammatory parameters and oxidative stress and improved insulin resistance and iron metabolism. Furthermore, SP effectively lowered the important gut-derived uremic toxins indoxyl and p-cresol sulfate. These improvements were associated with a better quality of life. Further controlled studies are required in a larger cohort to evaluate the clinical outcome.},
  language  = {en}
}
@article{ReineckeJuergensmeyerEngelbertzetal.2018,
  author    = {Reinecke, Holger and J{\"u}rgensmeyer, Sabine and Engelbertz, Christiane and Gerss, Joachim and Kirchhof, Paulus and Breithardt, G{\"u}nter and Bauersachs, Rupert and Wanner, Christoph},
  title     = {Design and rationale of a randomised controlled trial comparing apixaban to phenprocoumon in patients with atrial fibrillation on chronic haemodialysis: the AXADIA-AFNET 8 study},
  series = {BMJ open},
  volume    = {8},
  journal   = {BMJ open},
  number    = {9},
  doi       = {10.1136/bmjopen-2018-022690},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225156},
  pages     = {e022690, 1-10},
  year      = {2018},
  abstract  = {Introduction Patients with end-stage kidney disease requiring maintenance haemodialysis treatment experience a dramatic cardiovascular morbidity and mortality. Due to the high atherosclerotic and arteriosclerotic burden and profound alterations in haemostasis, they frequently suffer and die from both thromboembolic and bleeding events. This is a particular concern in patients on haemodialysis with atrial fibrillation (AF). Controlled trials on the optimal anticoagulation in patients with AF on haemodialysis are not available. The randomised controlled phase IIIb AXADIA-AFNET 8 trial will evaluate the safety and efficacy of the factor Xa inhibitor apixaban in patients with AF requiring haemodialysis. Methods and analysis A total of 222 patients will be randomised in an open-labelled, 1:1 design to receive either apixaban 2.5mg twice daily or dose-adjusted vitamin K antagonist therapy (target international normalised ratio 2.0-3.0). All patients will be treated and followed up for a minimum of 6 months up to a maximum of 24 months. The primary outcome is major or clinically relevant, non-major bleedings or death of any cause. Secondary outcomes include stroke, cardiovascular death and other thromboembolic events, thus exploring the efficacy of apixaban. The first patient was randomised in June 2017. Ethics and dissemination The study protocol was approved by the Ethical Committee of the Landesaertzekammer, Westfalen-Lippe and the Medical Faculty of the University of Muenster, Muenster, Germany (reference number: 2016-598f-A). Written informed consent will be obtained from all patients prior to study participation, including their consent for long-term follow-up. AXADIA-AFNET 8 is an investigator-initiated trial. Sponsor is AFNET, Muenster, Germany. Study findings will be disseminated to Bristol-Myers Squibb, Munich, Germany, and Pfizer, Berlin, Germany, to the participating centres, at research conferences and in peer-reviewed journals. Trial registration numbers NCT02933697, Pre-results.},
  language  = {en}
}