Clinical implications of the cross-talk between renin-angiotensin-aldosterone system and vitamin D-FGF23-klotho axis Keyzer, Charlotte

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University of Groningen Clinical implications of the cross-talk between renin-angiotensin-aldosterone system and vitamin D-FGF23-klotho axis Keyzer, Charlotte IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2015 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Keyzer, C. (2015). Clinical implications of the cross-talk between renin-angiotensin-aldosterone system and vitamin D-FGF23-klotho axis [Groningen]: University of Groningen Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 09-11-2018

Clinical implications of the cross-talk between renin-angiotensin-aldosterone system and vitamin D-FGF23-klotho axis Charlotte A. Keyzer

Keyzer, CA Clinical implications of the cross-talk between renin-angiotensin-aldosterone system and vitamin D-FGF23-klotho axis Dissertation University of Groningen, with summary in Dutch ISBN: 978-90-367-8264-7 (printed version) ISBN: 978-90-367-8263-0 (digital version) C.A. (Charlotte) Keyzer 2015 All rights reserved. No part of this publication may be reproduced, copied, modified, stored in a retrieval system or transmitted in any form without explicit prior permission of the author. Financial support by the University Medical Center Groningen, Research Institute GUIDE, University of Groningen, Dutch Heart Foundation, ZGT Academy and Dutch Kidney Foundation for the publication of this thesis is gratefully acknowledged. Financial support for the printing of this thesis was also kindly provided by: ABBVIE ABN AMRO ALEXION PHARMA B.V. AMGEN B.V. ASTELLAS PHARMA B.V. BIO-CONNECT DIAGNOSTICS B.V. CHIPSOFT B.V. NIERNIEUWS SHIRE Cover: Sensit_@rt_Studio and Douwe Oppewal Lay-out: Douwe Oppewal Printing: Michal Slawinsky, thesisprint.eu in Poland

Clinical implications of the cross-talk between renin-angiotensin-aldosterone system and vitamin D-FGF23-klotho axis Proefschrift ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen op gezag van de rector magnificus prof. dr. E. Sterken en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op maandag 16 november 2015 om 16:15 uur door Charlotte Antoinette Keyzer geboren op 8 juni 1987 te Eindhoven

Promotores Prof. dr. G.J. Navis Prof. dr. S.J.L. Bakker Copromotor Dr. M.H. de Borst Beoordelingscommissie Prof. dr. C.A.J.M. Gaillard Prof. dr. H.A.H. Kaasjager Prof. dr. P. de Vos

Paranimfen Mw. drs. L.V. de Vries Dhr. drs. L.H.J. Keyzer 5

CONTENTS Introduction 9 Part I - Clinical impact of targeting cross-talk: albuminuria and 27 renoprotective treatment Chapter 1 Plasma vitamin D level and change in albuminuria and egfr 29 according to sodium intake Clinical Journal of the American Society of Nephrology - accepted Chapter 2a Vitamin D receptor activator and dietary sodium restriction to reduce 45 residual urinary albumin excretion in chronic kidney disease (ViRTUE study): rationale and study protocol Nephrology Dialysis Transplantation - published online March 16, 2015 Chapter 2b Vitamin D receptor activation and dietary sodium restriction to reduce 59 residual albuminuria in chronic kidney disease: the ViRTUE randomised controlled trial Submitted Chapter 3 Serum soluble α-klotho during intensified renin-angiotensin-aldosterone 79 system blockade in non-diabetic chronic kidney disease In preparation Part II - Clinical impact of cross-talk: novel clinical readouts 93 and downstream factors Chapter 4 Calcification propensity and survival among renal transplant recipients 95 Journal of the American Society of Nephrology - published online April 29, 2015 Chapter 5 Vitamin K status and mortality after kidney transplantation: a cohort study 119 American Journal of Kidney Disease 2015; 65(3):474-483 Chapter 6 Associations of 25(OH) and 1,25(OH) 2 vitamin D with long-term outcomes 137 in stable renal transplant recipients The Journal of Clinical Endocrinology & Metabolism 2015; 100(1):81-89 Chapter 7 Serum Dickkopf-1, renal fibrosis and risk of graft failure after 155 kidney transplantation Submitted Summary, discussion and future perspectives 173 Nederlandse samenvatting / Dutch summary 189 Dankwoord / Acknowledgements 197 About the author 203 List of publications 205 7