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European Training and Research in Peritoneal Dialysis

Final Report Summary - EUTRIPD (European Training and Research in Peritoneal Dialysis)

European Training and Research in Peritoneal Dialysis; Scientific objectives, Training, Implementation and Impact of the programme.
Renal replacement therapy (RRT) is necessary for the survival of patients with end stage renal disease (ESRD) both prior to kidney transplantation or long-term in patients where kidney transplantation is not viable. Peritoneal dialysis (PD) and haemodialysis (HD) are life-saving RRTs for more than 200.000 patients with ESRD in Europe. As the incidence of chronic renal disease has doubled over the past decade, the number of patients with ESRD is expected to increase by 3-5 percent annually. The burden of ESRD is increasing with the ageing population across EU member states. Today, more than 5 billion Euros per year are spent on RRT in the EU member states and the social impact is very significant Long-term survival of PD and HD are similar, but there is an early patient survival advantage for home-based PD over the first 2-3 years of dialysis. Furthermore, a number of studies have shown that patients on PD can have a better quality of life than patients on HD performed three times per week in a dialysis centre. PD is an effective treatment for a wide range of patients from children to the elderly and is a more cost effective therapy compared to hospital-based HD in all health economic studies that have performed. Nevertheless, only one out of 10 patients on dialysis is treated with PD in EU member states that compares unfavourably with the much higher percentage of patients on PD in other parts of the world e.g. Canada, Australia and Hong Kong. In addition there is considerable variation within the EU from only 5% in Germany to 30% in Denmark. This suggests that the general underutilisation of PD in Europe is due to non-clinical factors such as the lack of clinical PD experience and knowledge by nephrologists. As a consequence, patients do not receive an informed choice about modality selection, and are thus deprived of the potential advantages of PD.

Goals and Objectives
The main challenge for the ITN project European Training and Research in Peritoneal Dialysis (EuTRiPD) was to identify diagnostic and therapeutic tools to improve PD outcomes by identifying mechanisms and interventions that promote survival and function of the peritoneal membrane and prevent infectious complications. This will lead to the improvement of the therapy in terms of allowing patients to remain on PD for longer, patient survival and the quality of the patients’ lives. Hence, EuTRiPD aimed to address the issue of underutilization of PD by training young multidisciplinary researchers who are specifically qualified to understand and work within and beyond all the disciplines, sectors and audiences of PD, in order to improve PD outcomes by developing future specific therapies in PD patients, a group of patients with a high risk of complication and comorbidity. The specific aim of the program was to develop a minimum of 5 biomarkers that allow the prediction of outcome in PD and 3 therapeutic treatments to improve outcome in PD. Both the treatments and biomarkers will have specific targets, be rigorously tested in lab based experiments and will be checked with clinical data from databases.

Indeed the programme has developed a minimum of 5 Biomarkers and 3 therapeutic treatments to improve PD. Biomarkers first defined are IL6, IL8, ex-vivo stimulated IL-6 release as well as IL-8 release, CA-125 and AOPP. Furthermore completely new we identified IL-17, M1/M2, Treg/Th17, miR 21 and miR 31.
Trials are the alanyl-glutamine (Ala-Gln) trial by MUW and Zytoprotec, the vitamin D trial by VUMC and Baxter and the fingerprints analysis in EMT trial by CSIC. In the paper attached to the report an elaborate description of the work can be read.

Collaboration between the academic and industrial EuTRiPD partners ensured these results were maximised to their full potential by large multi-centre clinical trials for testing of these new diagnostic and therapeutic tools. All the private sector partners have a keen interest to develop such new tools for PD patients and achieve marketing authorisation.
In addition the academic partners did expect improvements in healthcare in their respective clinical practice, increased knowledge and visibility of their expertise through publications and training experience. The active involvement of patient groups as associate partners did effectively increase knowledge of PD therapy and improve its accessibility for more patients and reduce health inequalities in EU member states.

EuTRiPD research has been structured into three work packages (WP), each using a multitude of different techniques to work towards finding biomarkers and therapeutic interventions. WP 1 focused on investigating cellular workings and the relationships between cell types relative to PD by looking at the cell signalling pathways. WP2 centred on in vivo modelling of the inflammation mechanisms in cutting edge rat and mouse models. WP3 targeted the Biobanks (clinical databases and biological samples) from PD patients in order to establish outcome data related to targets identified in WPs1 and 2.

Rationale of the training programme
To train a new generation of knowledgeable and well equipped PD specialists the EuTRiPD scheme provided a broad training program that included, in addition to core clinical skills and state-of-the-art PD research exposure, also commercial experience and public awareness. This programme did have a clear emphasis on providing translational training that integrated these different aspects and, by including academic, private and public sector partners, ESRs were exposed to the different sectors relevant in this field which helped develop the next generation of PD thought leaders .

Content and structure of the training programme
EuTRiPD provided the training of twelve Early Stage Researchers (ESRs) that primarily consisted of Training Through Research within their individual projects carried out mainly at the host institution, but also taking advantage of the knowledge and expertise of other network partners through secondments. In addition to the individual projects the ESRs attended the semi-annual EuTRiPD academy. These academies lasting of 3-5 days included intensive lectures, workshops and networking covering a wide variety of areas in PD research. These areas were not limited to purely research topics but also covered socio-economic, patient reported outcomes, and private sector interests. Complimenting these intensive lectures were Core-Day-Conferences (CDCs) during the academy. These featured guest speakers from different aspects of PD research; each CDC had a central theme, for example Encapsulating Peritoneal Sclerosis, a rare but particularly devastating complication of PD therapy. In addition the ESRs also attended Associate Training Modules provided by partners of EuTRiPD: Kidney Research UK, The Dutch Kidney Foundation and EuroPD. As part of their specific training ESRs attended local training courses at the institution in which they worked, or still work. ESRs also undertook short term stays with EuTRiPD partners to provide a broad knowledge of industry and academic work.
Furthermore complementary skills, like entrepreneurship, international networking, communication skills, and assessment of patient needs were taught in order to broaden the experience of ESRs and enhance their own networking and collaborative abilities.

EuTRiPD provides an interdisciplinary and cross sector long lasting training programme in PD research, addressing the need for skilled researchers, clinicians and nurses in renal disease. By carrying out focused bench to bedside research, and in turn developing therapeutics and identifying biomarkers, the project improved clinical out-comes and quality of life for CKD patients. As the Partners of the project agreed to carry on the work after the four years of EU support, the training programme will stay available for young researchers in the field of PD.
By keeping the EuTRiPD website intact, including the collaboration with EuroPD as well as the commitment and agreement of all present partners, the continuation of remaining this training and research programme is ensured.

Impact It was and still is EuTRiPD’s belief and mission to supply Europe with young, well trained professionals in renal research and PD with excellent intersectoral career options in the general medical research field, in order to improve patient outcomes and to address the general underutilization of PD across EU member states. EuTRiPD will make a committed contribution to booster currently hampered diagnostic and therapeutic developments in RRT in a unique long-lasting combined effort to structure existing high quality public and private sector PD related research across Europe. The impact of EuTRiPD on clinical (better survival) social (better quality of life of patients), economic (money-saving) and scientific aspects (coordinated, long-lasting and intersectoral research and training) therefore was and still can and will be enormous and sustainable.

Up to date information can be found on our project website