Improvement of the outcome of renal transplantation, for both recipients and living donors and through: Determine the cellular and molecular mechanisms leading to (the resolution of) graft failure after transplantation.
Translation of the knowledge from basic science to personalized medicine Exploring innovative therapeutic strategies, such as cell-based treatments, tissue engineering and novel drugs, in order to recover and preserve function of the renal graft. Expanding the donor pool in both living and deceased donation. Optimizing care and support for (living) donors and recipients.
The multidimensional research in our ACE ranges from fundamental to epidemiological. All research projects are multidisciplinary by nature. Being the most prominent (and scientifically prolific) transplant center in The Netherlands, we have collaborations with many other top scientific institutes, including Aarhus, Regensburg, Oxford, London, Birmingham, Bergamo, Edmonton, Stanford, Chengdu. We want to optimize and individualize immunosuppressive therapy, using biomarkers and immune monitoring and follow the evolution of the immune system throughout life, from naïve to exhausted. We are increasingly able to predict the individual risk of both rejection and drug-related side effects.
Improving long term graft and patient survival remains a challenge and we are exploring novel approaches/strategies for the prevention and treatment of chronic allograft deterioration that at the same have an improved safety profile. In order to expand the possibilities of using suboptimal organs for transplantation we are developing tissue repair strategies.
As the pool of living donors is restricted, we focus on innovative strategies to increase the possibilities of donation. We also study the application of home-based patient-directed education on knowledge of renal disease, the likelihood of living donor kidney transplantation and the promotion of medication adherence and self-management. In addition, the optimization of psychological well-being of living donors and recipients and the long-term outcome after living kidney donation is a subject of study.
Education within the ACE Kidney Transplantation spans the entire continuum from student to specialist physician. Apart from many regular lectures and workgroups within the Bachelor and Master curricula of the Erasmus MC medical school, members of our ACE are responsible for the Minor Kidney Transplantation.
Many students do electives (keuze onderwijs of keuze onderzoek) at our facilities, including many foreign students. Teachers from our ACE are also involved with the Research Master infection and immunity and the Junior Med School. All teaching is continuously evaluated using a well-defined PDCA cycle, and has (in general) received favorable reviews from the students.
The departments represented in our ACE host a large number of PhD students, which leads to a substantial teaching effort. Moreover, we are present in the teaching committee of and the Postgraduate school Molecular Medicine. We host many PhD students with international fellowships (CES, ERA-EDTA).
Postgraduate education is delivered both on a national (NTV, Transplant Seminars) and an international level (ESOT). We are highly involved in the medical specialty training, mainly for internal medicine, nephrology, surgery and pediatrics, all of which have periodic evaluations using both SET Q and D-RECT instruments. Following registration many surgeons visit our department for courses at our skills lab (LIDO course).
Societal Relevance to Research, Education and Patient Care
Compared to dialysis, renal transplantation is considerably less expensive. Promotion of transplantation in patients with renal failure, optimization of organ quality and treatment for transplant recipients leading to better graft and patient survival, leads to a reduction in costs for the society.
ACE members contribute to public health by raising awareness in the general population of the possibility to improve daily life and life-expectancy of patients with organ failure by means of patient-specific websites, home-based education and by patient meetings (patients, relatives and friends), also in surrounding hospitals. Members of our ACE contribute to national guidelines on care for transplant recipients and donors, as well as to international educational programs (e.g. ESOT educational platform).
Our lectures and elective programs are considered a cornerstone of the medical curriculum. Members of our ACE have developed a tool and associated procedures for psychosocial screening of living kidney and liver donors, that is being implemented throughout Europe (ELPAT project) After having pioneered home-based education of patients within their social system, we currently coordinate the ZIN sponsored implementation of this strategy in 4 renal transplant centers and associated dialysis facilities, with the intention of setting a new standard of care in The Netherlands.
Viability of Research, Education and Patient Care
The ACE has a research culture that is based on multidisciplinary collaboration. The collaboration between departments that form the core of this ACE has been in place for more than twenty years and has proven exceedingly productive. An extensive bibliometric analysis (performed using Web-of-Science data and VOSviewer) did not fit the format of this application and is available upon request.
Our combined research has led to a position that is recognized internationally and that will yield favorable results in any form of benchmarking, both clinically and scientifically. As a result, this ACE will be capable of meeting its targets in research and society. Also, emphasis has been placed on the governance and leadership within the ACE's management, with the primary objective to develop talent within the group and to attract talent from elsewhere .
As a result, many of our PhD students have pursued an international scientific career and, in doing so, have strengthened our international network.
Key and relevant publications of the last five years
- Roemeling-van Rhijn M, Reinders ME, de Klein A, Douben H, Korevaar SS, Mensah FK, Dor FJ, IJzermans JN, Betjes MG, Baan CC, Weimar W, Hoogduijn MJ. (2012) Mesenchymal stem cells derived from adipose tissue are not affected by renal disease. Kidney Int. 82: 748-58.
- Hoogduijn MJ, Verstegen M, Engela AU, Korevaar SS, Roemeling-van Rhijn M, Merino A, Franquesa M, de Jonge J, IJzermans JN, Weimar W, Betjes MG, Baan CC, van der Laan LJ. (2014). No Evidence for Circulating Mesenchymal Stem Cells in Patients with Organ Injury. Stem Cells Dev. 23(19):2328-2335.
- Franquesa M, Mensah FK, Huizinga R, Strini T, Boon L, Lombardo E, DelaRosa O, Laman JD, Grinyó JM, Weimar W, Betjes MG, Baan CC, Hoogduijn MJ. (2015). Human adipose tissue-derived mesenchymal stem cells abrogate plasmablast formation and induce regulatory B cells independently of T helper cells. Stem Cells 33(3):880-891.
- NM van Besouw, K Caliskan, AMA Peeters, M Klepper, M Dieterich, APWM Maat, W Weimar, OC Manintveld, CC Baan. (2015). Interleukin-17-producing CD4+ cells home to the graft early after human heart transplantation. J Heart Lung Transplant; 24: 933-940
- Peters, F.S., Manintveld, O.C., Betjes, M.G., Baan, C.C. and Boer, K. (2016). Clinical potential of DNA methylation in organ transplantation. J Heart Lung Transplant.
- Litjens NH, Boer K, Betjes MG. Identification of circulating human antigen-reactive CD4+ FOXP3+ natural regulatory T cells. J Immunol. (2012) Feb 1;188(3):1083-90.
- Bouvy AP, Klepper M, Kho MM, Boer K, Betjes MG, Weimar W, Baan CC. (2014).The impact of induction therapy on the homeostasis and function of regulatory T cells in kidney transplant patients. Nephrol Dial Transplant. 29(8):1587-97.
- Timmerman L, Laging M, Westerhof GJ, Timman R, Zuidema WC, Beck DK, IJzermans JNM, Busschbach JJV, Weimar W, Massey EK. (2015). Mental health among living kidney donors: A prospective comparison with matched controls from the general population. Am J Transplant; 15: 508-17
- Jongbloed F, de Bruin RW, Klaassen RA, Beekhof P, van Steeg H, Dor FJ, van der Harst E, Dollé ME, IJzermans JN. (2016). Short-Term Preoperative Calorie and Protein Restriction Is Feasible in Healthy Kidney Donors and Morbidly Obese Patients Scheduled for Surgery. Nutrients. 20;8(5).
- Saat TC, van den Akker EK, IJzermans JN, Dor FJ, de Bruin RW. (2016). Improving the outcome of kidney transplantation by ameliorating renal ischemia reperfusion injury: lost in translation? J Transl Med. ;14:20.
PhD theses of the last five years
- A.P. Bouvy - Immune modulation after T-cell depletion therapy in kidney transplant patients - 2016
- M. Tielen - Psychosocial aspects of medication nonadherence after kidney transplantation - 2016
- M.W.H.J. Demmers - Human tubular epithelial cells and T-cell alloreactivity - 2015
- R.W.J Meijers - Uremia-associated T-cell ageing with regard to kidney transplantation - 2015
- L. Timmerman - Exploring the mental health of living kidney donors - 2015
- S. Ismail - Home-based education increases knowledge, communication and living donor kidney transplantations - 2015
- J. Lafranka - Shifting Paradigms in Live Kidney Donation and Transplantation - 2015
- M. Roemeling – van Rijhn - Towards mesenchymal stem cell therapy in kidney transplant recipients - 2014
- K.W. Klop - Tailor-Made Live Kidney Donation - 2014
- N. Dols - Optimizing living donor nephrectomy - 2013