Chairs: W. Ramlow (Rostock, Germany), A. Handisurya (Vienna, Austria)
|Plasmaseparation, is there a difference in technologies?
1 Klinikum Braunschweig, Med. Klinik V, Braunschweig, Germany
Abstract text :
|Immunoadsorption in CIDP and steroid-refractory MS relapse
1 RKU – Universitäts- und Rehabilitationskliniken Ulm gGmbH, Neuromuskuläres Zentrum, Ulm, Germany
Abstract text :
Immunoadsorption is a promising therapy for a wide spectrum of neurological autoimmune diseases, but to date evidence is generally low, especially with regard to chronic diseases without a specific autoimmune antibody like MS and CIDP.
In steroid-refractory MS relapse, several case series exist which show a response rate about 75% and a better outcome when immunoadsorption is applied early. A randomized controlled study comparing immunoadsorption and plasma exchange will be completed in 2018. Another randomized controlled study within the German MS network comparing immunoadsorption and ultra-high dose methyl-prednisolone is expected to start this year. There are no studies investigating IA in chronic-progressive MS forms, although pathophysiological considerations suggest that regular IA might be effective here as well.
In CIDP, short-term and long-term effects have to be considered. Only few case series exist, which generally show small transient improvements after IA in most patients. However, regular IA every 2-3 months might stabilize progressive cases of CIDP and lower the need of immunosuppressive drugs.
|Removal of phospholipase A2-receptor antibodies in subjects with primary membranous nephropathy by immunoadsorption
1 Medical University of Vienna, Department of Medicine III, Division of Nephrology and Dialysis, Vienna, Austria
2 Medical University of Vienna, Department of Pathology, Vienna, Austria
3 University Medical Center Hamburg-Eppendorf, III. Department of Internal Medicine, Hamburg, Germany
4 Medical University of Vienna, Department of Laboratory Medicine, Vienna, Austria
5 Medical University of Vienna, Department of Emergency Medicine, Vienna, Austria
Abstract text :
70% of all individuals with primary membranous nephropathy (MN) feature circulating phospholipase A2-receptor-antibodies (PLA2R-Ab) which are linked to pathogenicity and course of the disease.
To evaluate whether immunoadsorption (IA) efficiently removes circulating anti-PLA2R-Ab and ameliorates proteinuria, four individuals with biopsy-proven primary MN, positive serum anti-PLA2R-Ab, and nephrotic-range proteinuria were treated with IA using Globaffin adsorbers (Fresenius Medical Care & Co). In total, 22-42 sessions of IA, each with a processed plasma volume of 7200-8000 mL, were performed over a period of 68-366 days followed by six cycles of combination therapy consisting of two IA plus rituximab (375 mg/m² body surface) within three consecutive days. The mean follow-up period was 420.5±62.3 days.
All subjects achieved partial remission (PR) according to the KDIGO-definition at the end of the study with reductions of serum PLA2R-Ab levels by 91.1±14.3% (range: -69.0 to -99.2%) and urinary protein-creatinine-ratio (uPCR) by 77.3±14.3% (range: -59.7 to -94.6%) compared to their respective maximal values. IA effectively removed PLA2R-Ab from circulation with continuous reduction of serum PLA2R-Ab levels, if IA was performed daily, positive PLA2R-Ab measurement in eluate samples, and substantial decrease of circulating PLA2R-Ab concentrations post- vs. pre-IA. After adjustment for serum PLA2R Ab levels, a linear random effects model only showed a tendency towards a lower average uPCR following IA-monotherapy (p=0.108), but a significant attenuation after the combination of IA plus rituximab (p=0.034). Notably, this regimen of IA plus rituximab improved the outcome even in participants who had previously not responded to rituximab treatment.
IA removed anti-PLA2R-Ab from circulation and, in combination with rituximab, sustained antibody removal in primary MN. Furthermore, IA seems to support and improve beneficial rituximab-effects in known rituximab non-responders with primary MN.
|Selective apheresis of C-reactive protein. A promising therapeutic option in acute myocardial infarction.First results of the CAMI1-study
1 Diako Flensburg, Medical Clinic, Flensburg, Germany
2 Charité-Universitätsmedizin Berlin, Medizinische Klinik m.S. Nephrologie und Internistische Intensivmedizin, Berlin, Germany
3 Vivantes Klinikum Neukölln, Berlin, Klinik für Kardiologie, Angiologie, Nephrologie & kons. Intensivmedizin, Berlin, Germany
4 Cardiovascular Center Oberallgäu-Kempten, und MVZ-Kempten, Kempten, Germany
5 Herzzentrum Dresden, , Dresden, Germany
6 Universitätsmedizin Rostock, , Rostock, Germany
Abstract text :
Background: The treatment of acute ST-Elevation Myocardial Infarction (STEMI) is based on early recanalization of the occluded coronary artery to limit myocardial damage. It is well known that high serum levels of C-reactive protein (CRP), are associated with postinfarct morbity and mortality. CRP may contribute to myocardial damage in STEMI by activating the complement system. In animal experiments, injection of human CRP enhanced infarct size and complement depletion reduces infarct size and results in a significantly better left ventricular ejection fraction (LVEF). The new developed CRP adsorber (PentraSorb® CRP) allows selective removal of CRP in humans. Here, we present preliminary data of the ongoing human multi-center study CRP-apheresis in Acute Myocardial Infarction (CAMI1).
Methods: After complete coronary revascularization, 23 Patients with STEMI received CRP apheresis, whereas 23 patients treated by standard protocols served as matched controls. CRP apheresis was performed 24(±12) hrs and 48 hrs after onset of symptoms via peripheral venous access. In case of an increase of serum level in CRP >30 mg/l following the second session, a third treatment was carried out 24 hrs later. In each apheresis session 6000 ml plasma were treated. Primary study endpoint was myocardial infarction size as determined by Cardiac Magnetic Resonance Imaging (MRI) 5±3 days and 12±2 weeks after STEMI
Results: The CRP baseline levels were 25 mg/l (median) (range 12-279 mg/l). CRP apheresis resulted in an average 64 % reduction in CRP plasma levels. Myocardial infarct size in the CRP apheresis-treated STEMI patients was 51% smaller (p = 0.0035) compared to controls, and circumferential strain was 12% (p = 5x10-10) better while the longitudinal strain was 17% (p = 9x10-11) better. In the follow-up period (≤ 12 months), 3 major adverse cardiac events (MACE) occurred in the control group and none in the CRP apheresis group. Apheresis sessions were well tolerated with moderate adverse events. There were only one study discontinuation after the first apheresis treatment due to problems with peripheral venous access. Five dropouts due to problems with MRI.
Conclusion: CRP apheresis following STEMI seems feasible and safe. First results show a significant beneficial effect on myocardial infarction size and wall motion. Selective CRP apheresis is a promising new therapeutic approach in the treatment of acute myocardial infarction.