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Identification and Management of Patients at Risk – Outcome and Vascular Events in Peritoneal Dialysis

Periodic Reporting for period 1 - IMPROVE-PD (Identification and Management of Patients at Risk – Outcome and Vascular Events inPeritoneal Dialysis)

Reporting period: 2019-01-01 to 2020-12-31

Peritoneal dialysis (PD) is a life-saving renal replacement therapy (RRT), for the increasing number of Europeans suffering end-stage kidney disease, from infants to geriatrics. Although PD offers socio-economic and performance benefits over haemodialysis (HD), both RRTs severely accelerate atherosclerotic disease progression and cardiovascular outcomes, when compared with pre-dialysis renal patients. Most notably, in PD patients there is an excessive risk of inflammation-driven cardiovascular disease, which is strongly linked to mortality2. Improved understanding of the molecular mechanisms involved in PD-related local and systemic inflammation, and their connection with cardiovascular outcomes will help in the design of interventions that substantially reduce the risk of these PD-related complications. There is an urgent need within Europe for inter-sectoral research in this area and for well-trained researchers with appropriate expertise and multidisciplinary skills to drive improvements in PD therapy.

In addition, there is an unmet need for a risk-adjusted individualized PD approach to tackle current limitations in PD therapy and to transform understanding of how local inflammation may drive cardiovascular pathology. In this context, PD offers the unique opportunity of a direct route to the peritoneal immune system and to tissue-resident cells, facilitating the study of pathophysiological mechanisms and the exploration of novel approaches to local fibrosis/inflammatory-modulatory therapies. Only close collaboration between industrial and academic sectors, and working in partnership with patients and public, will achieve these ambitious scientific and clinical targets.

The IMPROVE PD consortium connects leading academic and industrial researchers in this field internationally, who will cooperate in the shared goal of understanding the mechanisms of inflammation-driven cardiovascular disease in PD patients, developing individualized approaches to identify those at risk, and testing new therapies in them. IMPROVE-PD will offer 15 young scientists who will work in close partnership in 11 institutions located in 7 different countries in an excellent, multidisciplinary and intersectoral pan-European PhD-level training programme delivered by leading academic, clinical and industrial stakeholders. Network-wide and local training activities including academies and satellite modules associated with large nephrology conferences, combined with individual research projects, intersectoral secondments and short laboratory visits, will provide key generic skills including valorisation, entrepreneurship and intellectual property management and will prepare early stage researchers for future roles as highly skilled research leaders in Europe.
The following activities were carried out so far:

• Coordinated recruitment process implemented: The IMPROVE-PD recruitment strategy was designed to recruit excellent earsy stage researchers through coordinated activity across beneficiaries, partner organisations, and their other external collaborators. Researchers were selected through an open, informed, efficient and transparent recruitment and evaluation process.

• High quality supervision scheme established: The supervisory team of each, chosen on the basis of its complementary skills and expertise, ensures the intellectual enrichment of each early stage researchers' individual project by allocating academic and industrial mentors.

• Individual and Personalised Career Development Plan are developed and being updated as needed: Besides skills requirements for carrying out the research projects, the PCDP contain training aspects in the academic, industrial and clinical sectors intended for intersectoral preparation of the early stage researchers for their future career in any of these fields.

• Network-wide intensive training programme was established and is being implemented: 3 Academies and 2 online webinars-masterclasses were organised to provide interdisciplinary and intersectoral training across all aspects required by the early stage researchers.
With the ageing European demographic, the number of people affected by chronic diseases, and eventually organ failure is growing. PD represents an efficient and cost-effective treatment option that can be performed as a home therapy without constant assistance, representing a potential for relief of patients and the European health care systems. Kidney damage is a major risk factor for cardiovascular disease, which is poorly addressed by current therapies. PD enables study of a subgroup of patients at especially high risk of disabling cardiovascular disease and death, allowing for an extreme of phenotype approach to understanding pathology. Europe needs well-trained researchers able to address these challenges and opportunities, but relevant training is scarce.

IMPROVE-PD provides excellent training through research in leading laboratories across Europe, together with enrolment in established and highly regarded local PhD training programmes. Each early stage researcher is placed in a local environment that nurture their talents as a researcher. The personal development and creativity of the fellows is further stimulated in network-wide meetings, where the early stage researchers present and discuss their work in review meetings led by active and productive senior researchers in the field. Twinning of training events with relevant conferences gives all early stage researchers the experience of presenting to large international meetings, and the opportunity to interact and network with scientific, clinical and industrial experts.

Network-wide meetings provide a dedicated programme of training for the early stage researchers. Six core skills modules are expected to ensure that all early stage researchers understand the whole research programme of IMPROVE-PD. Six complementary skills courses are to help the early stage researchers develop the additional skillsets such as managing one’s own personal development, team working, entrepreneurship, good clinical practise in translational research, and making funding and job applications. Seven intersectoral courses led by experts introduce to them the best approaches to patient needs and public awareness, working with and in SMEs and large industrial entities, the translational pipeline from the industrial perspective, and marketing.

The intense co-operation with industrial partners adds a key dimension to the early stage researchers’ training and makes the early stage researchers well aware of the real processes (and challenges) by which basic experimental and clinical data is translated into patient care and newly developed therapies. 4 early stage researchers are primarily based with an industrial partner, and all other early stage researchers are expected to spend 2 or more months based at an industrial partner on secondment during their project. There is in addition a prominent contribution of the intersectoral partners to the IMPROVE-PD academies, which stimulate the early stage researchers’ entrepreneurship and equip them with a unique transferable skillset to improve employability and open private sector career opportunities. Moreover, the direct involvement of public partners Kidney Research UK, EuroPD and the DKF in the IMPROVE-PD training programme adds another aspect to the early stage researchers' employability.
IMPROVE-PD consortium, Academy in Madrid