Our ACE has three primary aims:
- To align and integrate academic patient care with research and education (for patients and professionals).
- To deliver multi-disciplinary tertiary care to pediatric and adult patients with kidney disease and/or hypertension concentrating on patient-centered outcomes.
- To focus on three well-defined groups of disorders for which tertiary care is indicated and which fit into our lines of research: (1) renal tubular & electrolyte disorders, (2) resistant hypertension, (3) renal cystic disease.
All research activities within our ACE focus on kidney and hypertension and our approach meets the requirements for both multidimensionality (all 4 levels) and multidisciplinarity (11 involved departments).
The research objectives of our ACE are as follows:
- To maintain our successful research line on hypertension and the renin-angiotensin system (prof. Danser, dr. van den Meiracker, dr. Hoorn, prof. Zietse, dr. Friesema, dr. Versmissen, dr. Visser; Currently 6 PhD-students, linked to COEUR, level: Translational & Clinical). A future aim is to further develop a research line with Clinical Pharmacology and Hospital Pharmacy on therapeutic drug monitoring and drug adherence in hypertension (dr. van den Meiracker, prof. van Gelder, dr. Versmissen).
- To maintain and further develop our emerging research line renal tubular disorders (dr. Hoorn & prof. Zietse, Currently 7 PhD-students, linked to MolMed, Erasmus MC number MM-04-39-10; level: Translational & Clinical). On a more fundamental level, we collaborate with the Departments of Cell Biology (dr. Jansen) and Developmental Biology (prof. Gribnau) on cystogenesis and kidney organoids (in collaboration with Hubrecht Institute, Utrecht, 1 shared PhD-student).
- To further increase our involvement in the Rotterdam Study with regard to population-based studies in which electrolyte disorders, hypertension or kidney disease are determinants or outcomes (collaborations prof. Stricker, dr. Dehghan, dr. Hoorn, prof. Zietse, dr. Mattace-Raso, currently 4 shared PhD-students, level: epidemiological).
- To maintain and renew participations in national consortia with regard to clinical trials and novel therapeutics in nephrology (through the Dutch Kidney Foundation consortia program). Currently involved in the national DIPAK-study (prof. Zietse & dr. Hoorn, www.nierstichting/dipak) and the RESTERN-study (drs. Dorresteijn).
- To pursue new therapeutic strategies for resistant hypertension, including renal denervation and carotid baroreceptor stimulation (collaborations vascular medicine, intervention radiology, vascular surgery: dr. van den Meiracker, dr. Versmissen, dr. Moelker, prof. Hendriks).
- Examples of national and international collaborations with other top scientific institutes include the Radboudumc (profs. Bindels & Hoenderop, dr. Deinum, dr. Schreuder), University of Aarhus (prof. Fenton), University College London (profs. Kleta & Unwin), National Institutes of Health USA (dr. Knepper), Oregon Health & Science University (prof. Ellison), University of Gent (prof. van Biesen), Max Delbrück Center for Molecular Medicine (prof. Müller), Vanderbilt University (prof. Moslehi), and the University of Zürich (prof. Devuyst, prof. Löffing, prof. Wagner).
Our ACE is actively involved in education at the following levels:
- The medical curriculum: both bachelor and master. Current participation consists of Theme Coordination (Theme Ba1B, prof. Zietse), Research Masters Infection & Immunity (prof. van Gelder) and Molecular Medicine (co-director dr. Jansen), Minor Internal Medicine (dr. van den Meiracker, dr. Hoorn, dr. Versmissen), and Clinical Reasoning (several participants). Several participants also lecture in the master phase (mainly Ma1B). Prof. Zietse and dr. Versmissen will coordinate the master phase of the Erasmus 2020 program.
- The residency program internal medicine and the fellowships in (pediatric) nephrology and vascular medicine. Prof. Zietse is a member of the Concilium Medicinae Internae. In collaboration with the Dutch Internist Society (NIV), we organize a national educational course for residents in internal medicine (COIG, twice yearly, approx. 250 participants, prof. Zietse & dr. Hoorn, since 2010), and local education to residents (dr. Versmissen, drs. Dorresteijn). Several participants are also involved in national education of fellows in nephrology (drs. Dorresteijn, dr. Hoorn, prof. Zietse) and vascular medicine (dr. van den Meiracker, dr. Versmissen).
- PhD and postgraduate education on Kidney & Hypertension. Current initiatives include the Rotterdam Course in Electrolyte and Acid-Base Disorders (since 2009, yearly, approx. 120 participants), positions in the faculty of the international course "Applied Renal Physiology" (since 2007, yearly, University College London), Erasmus Endocrinology Course (prof. Zietse, dr. Hoorn, dr. van den Meiracker, since 2009) and the Dutch Kidney Foundation Winterschool (4-day course for PhD-students in nephrology, yearly, chaired by dr. Hoorn). In addition, our PhD-students follow their courses through our participation in the research schools MolMed and COEUR. Dr. van den Meiracker organizes the COEUR-course Vascular Medicine.
- Over the last few years, our ACE welcomed 7 international PhD-students, 1 visiting postdoc, and 2 visiting physicians.
Societal Relevance to Research, Education and Patient Care
- Development of Guidelines: Several, including the European Hyponatremia Guideline in 2014 (prof. Zietse & dr. Hoorn), the Dutch NIV guideline on electrolyte disorders (prof. Zietse & dr. Hoorn), the Dutch guideline for hypertensive emergencies (dr. van den Meiracker), the Dutch guideline on contrast nephropathy (dr. van den Meiracker), the care standard nephrotic syndrome by VSOP and the NVN (Dutch Kidney Patient Society; drs. Dorresteijn, dr. Betjes). Finally, we will chair the European Renal Best Practice Guideline on potassium balance disorders, which is scheduled for 2017.
- Public Health: Our ACE participates in educational activities during the annual World Kidney Day (each 2nd Thursday in March) and World Hypertension Day (each year on 17 May). These activities are crucial to increase awareness for the public health aspects of kidney and hypertensive disease.
- Public Health/Prevention: Our ACE (dr. Hoorn) contributed to the factsheet on dietary sodium intake by the Dutch Kidney Foundation: https://www.nierstichting.nl/media/filer_public/cb/d5/cbd5f27a-1252-4918-a46d-5a65ed4e5c34/factsheet_9_zout.pdf. Reducing dietary sodium intake is an effective non-pharmacological approach to reduce cardiovascular risk. Dietary adjustments require active patient participation and therefore contributes to patient empowerment.
- Innovation in Research: Our ACE is involved in the formation of a national research network and infrastructure for Dutch nephrology studies (NOVO-network and Nephron). • Innovation in Education: Several e-learning modules have been developed by the PIs of this ACE, including several YouTube tutorials by prof. Zietse and accredited e-learning modules on electrolyte disorders by dr. Hoorn and prof. Zietse (http://lms.medschool.nl)
Viability of Research, Education and Patient Care
We believe the viability of our ACE can be increased by collaborations with local hospitals to optimize tertiary referrals. On a national level we will pursue collaboration with centers involved in patient care of similar diseases (as is currently already in place for renal tubular disorders). On a European level we aim to connect to the European Reference Networks. Below we give a number of specific examples that illustrate the viability of our ACE:
- Balanced advanced knowledge sharing: Several multidisciplinary meetings are integrated within our ACE, including the research meetings of the Danser lab (weekly) and Hoorn-Zietse lab (weekly), MDO of vascular specialties (weekly), renal pathology meeting (weekly), MDO between adult nephrology, pediatric nephrology and clinical genetics (monthly), MDO between nephrology and urology (bi-monthly)
- Talent Identification: The laboratories in our ACE have hosted several Research Master students (each 1 year), of which three have continued into a PhD-program.
- International Exposure: In our ACE, seven international PhD-students completed their PhD. Several of our ACE-participants have international working experience (prof. Danser, prof. Gribnau, prof. Van Gelder, dr. Hoorn, dr. Versmissen, dr. Betjes), resulting in a large international network. Several ACE-participants have been or are currently involved in the development of international guidelines.
- Bibliometric Network Analysis: The visual outputs of the bibliometric network analysis of our ACE is available upon request (using VOSviewer). The PIs of our ACE have the following metrics: prof. Zietse (H-index 34, 164 publications), dr. van den Meiracker (H-index 33, 222 publications), dr. Hoorn (H-index 25, 117 publications), dr. Cransberg (H-index 15, 63 publications).
Key and relevant publications of the last five years
- Hoorn EJ, Monserez DA, Fenton RA, Overdevest I, Apperloo AJ, Zietse R, Hardillo JA. Olfactory Neuroblastoma With Hyponatremia. J Clin Oncol 2015; 33: e88-92.
- Zwiers AJ, IJsselstijn H, van Rosmalen J, Gischler SJ, de Wildt SN, Tibboel D, Cransberg K. CKD and hypertension during long-term follow-up in children and adolescents previously treated with extracorporeal membrane oxygenation. Clin J Am Soc Nephrol. 2014; 9: 2070-8.
- Danser AH, Anand P. The angiotensin II type 2 receptor for pain control. Cell. 2014; 157: 1504-6.
- Kidney Function and Cerebral Blood Flow: The Rotterdam Study. Sedaghat S, Vernooij MW, Loehrer E, Mattace-Raso FU, Hofman A, van der Lugt A, Franco OH, Dehghan A, Ikram MA. J Am Soc Nephrol. 2016; 27: 715-21.
- Atiq F, van den Bemt PM, Leebeek FW, van Gelder T, Versmissen J. A systematic review on the accumulation of prophylactic dosages of low-molecular-weight heparins (LMWHs) in patients with renal insufficiency. Eur J Clin Pharmacol. 2015; 71: 921-9.
- Van der Lubbe N, Lim CM, Fenton RA, Meima M, Danser AH, Zietse R, Hoorn EJ. Angotensin II induces phosphorylation of the thiazide-sensitive sodium chloride cotransporter independent of aldosterone. Kidney Int 2011; 79: 66-76.
- te Riet L, van Esch JHM, Roks AJM, van den Meiracker AH, Danser AHJ. Hypertension: renin-angiotensin-aldosterone system alterations. Circ Res 116: 960-975, 2015.
- Sevá Pessôa B, van der Lubbe N, Verdonk K, Roks AJ, Hoorn EJ, Danser AH. Key developments in renin-angiotensin-aldosterone system inhibition. Nat Rev Nephrol 2013; 9: 26-36.
- Salih M, Demmers JA, Bezstarosti K, Leonhard WN, Losekoot M, van Kooten C, Gansevoort RT, Peters DJ, Zietse R, Hoorn EJ; DIPAK Consortium. Proteomics of Urinary Vesicles Links Plakins and Complement to Polycystic Kidney Disease. J Am Soc Nephrol 2016 Mar 3 (epub).
- Hoorn EJ, Walsh SB, McCormick JA, Fürstenberg A, Yang CL, Roeschel T, Paliege A, Howie AJ, Conley J, Bachmann S, Unwin RJ, Ellison DH. The calcineurin inhibitor tacrolimus activates the renal sodium chloride cotransporter to cause hypertension. Nat Med. 2011; 17: 1304-9.
PhD theses of the last five years
- Van der Lubbe N, 29 October 2014: The aldosterone paradox: differential regulation of the sodium chloride cotransporter. Zietse R (promotor), Hoorn EJ (co-promotor).
- Verdonk K, 3 June 2015: Preeclampsia, the renin-angiotensin-aldosterone system and beyond. AHJ Danser, EAP Steegers (promotores), AH van den Meiracker, W Visser (co-promotores)
- Lankhorst S, 27 January 2016: Hypertension and renal toxicity during angiogenesis inhibition: salt dependency and treatment options. AHJ Danser (promotor), AH van den Meiracker (co-promotor)
- Zwiers AJM, 17 June 2015: Do not squeeze the kidneys: acute kidney injury in critically ill children. Tibboel D (promotor), Cransberg K, de Wildt SN (co-promotores).
- Jansen PM, 12 June 2013: The role of aldosterone and aldosterone blockade in hypertension. AHJ Danser (promotor), AH van den Meiracker (co-promotor).
- Sedaghat S, 23 September 2015: The kidney and the brain: role of vascular dysfunction. OH Franco Duran (promotor), A Dehghan, MA Ikram (co-promotores).
- Van Blijderveen N, 9 December 2014: Drug-related kidney injury and safe pharmacotherapy in the elderly. BHCh Stricker, Sturkenboom MCJM (promotores), KMC Verhamme, SMJM Straus (co-promotores).
- Tripepi GL, 12 September 2012: Age-related and prognostic risk factors in dialysis patients. EJ Sijbrands (promotor), FUS Mattace-Raso (co-promotor).
- Oluwatoroti Umuerri, 12 September 2012: Caenorhabditis elegans response to NaCl. FG Grosveld (promotor), G Jansen (co-promotor).
- Xifeng Lu, 8 January 2014: The (Pro)renin Receptor: Moving away from Prorenin? AH Danser (promotor), ME Meima (co-promotor)
Non-scientific publications related to the ACE
- M.G.H. Betjes
- A.S. Brooks
- M.C. Clahsen-van Groningen
- K. Cransberg
- A.H.J. Danser
- H. de Jong
- A. Dehghan
- E.M. Dorresteijn
- R.A. Feelders
- E.C.H. Friesema
- J. Gribnau
- J.M. Hendriks
- M.J. Hoogduijn
- G. Jansen
- F.U.S. Mattace Raso
- A. Moelker
- C.R.B. Ramakers
- S. Sedaghat
- B.H.C. Stricker
- M. van Agteren
- P.L.A. van Daele
- M.W.F. van den Hoogen
- A.H. van den Meiracker
- A.J. van der Heijden
- T. van Gelder
- P.C.M.S. Verhagen
- W. Visser
- W.E. Visser
- M.C. Zillikens
- Register as investigator