Serum calcification propensity is associated with renal tissue oxygenation and resistive index in patients with arterial hypertension or chronic kidney disease Menno Pruijm a , Yimin Lu a , Fatma Megdiche a , Maciej Piskunowicz a,c , Bastien Milani a,e , Matthias Stuber e , Matthias Bachtler b , Bruno Vogt d , Michel Burnier a , and Andreas Pasch b,f Background: Arterial calcifications increase arterial stiffness and are associated with a faster decline of kidney function in patients with arterial hypertension (AH) and/or chronic kidney disease (CKD). Yet the underlying mechanisms linking arterial calcifications, vascular stiffness and renal function decline are incompletely understood. A novel in-vitro blood test evaluates the propensity of patient’s serum to prevent the formation of calcifications by measuring the maturation time of calciprotein particles (CPP) [transformation time of amorphous calcium phosphate-containing primary CPP to crystalline hydroxyapatite-containing secondary CPP (T 50 )]. We hypothesized that a high arterial stiffness and a high propensity to calcify may be associated with high renal vascular resistance and low renal tissue oxygenation. Methods: T 50 was measured in patients with AH and a preserved renal function, in CKD patients and in healthy controls, a lower T 50 indicating a higher risk of calcification. Pulse wave velocity (PWV) was assessed as a measure of arterial stiffness, and renal resistive index was measured by renal Doppler ultrasound. Renal tissue oxygenation was measured by blood oxygenation level- dependent MRI using the mean R2  values of the cortex, the medulla and layers of renal parenchyma. A high R2  value corresponds to a low tissue oxygenation. Results: Mean T 50 was 246  129 min in 58 CKD patients, 275  111 min in 48 AH patients and 324  96 min in 39 healthy controls (P anova ¼ 0.008). In multivariable adjusted linear regression analysis, serum T 50 correlated negatively with circulating calcium and phosphate levels, mean cortical and medullary R2  , PWV, renal resistive index and being hypertensive. PWV was positively associated with R2  levels of outer and inner layers of renal parenchyma. Conclusion: The current study shows that hypertensive patients with preserved renal function as well as CKD patients have a higher risk of calcification than controls. High arterial stiffness and calcification propensity are linked to low renal tissue oxygenation and perfusion in hypertensive and CKD patients. These results provide new insights on the relationships among arterial stiffness, renal tissue oxygenation and the risk of developing CKD. Keywords: arterial stiffness, blood oxygenation level- dependent MRI, calcification propensity, chronic kidney disease, pulse wave velocity, transformation time of amorphous calcium phosphate-containing primary calciprotein particles to crystalline hydroxyapatite- containing secondary calciprotein particles test Abbreviations: AH, arterial hypertension; Aix, augmentation index; BOLD-MRI, blood oxygenation level- dependent MRI; CKD, chronic kidney disease; PWV, pulse wave velocity; RRI, renal resistive index; T 50 , transformation time of amorphous calcium phosphate-containing primary calciprotein particles (CPP) to crystalline hydroxyapatite- containing secondary CPP INTRODUCTION A rterial hypertension (AH) is a global health problem with a high cardiovascular morbidity and mortality. AH is also a well known risk factor for the develop- ment and progression of chronic kidney disease (CKD) [1]. The prevalence of CKD and AH are rising, largely because of the aging of the population [2]. Both disease states are closely entangled. Indeed, the majority of CKD patients suffer from AH, and AH is held responsible for 30% of the patients that develop end stage renal disease [3]. In addition, an optimal control of blood pressure (BP) will retard the decline of renal function in proteinuric CKD patients [4]. Accelerated atherosclerosis is mainly present in AH, whereas atherosclerosis and arteriosclerosis (media calci- fication) are both present in CKD. Arterial stiffening is a key feature of atherosclerosis and arteriosclerosis [5]. Clinical Journal of Hypertension 2017, 35:000–000 a Service of Nephrology and Hypertension, CHUV, Lausanne, b Department of Clinical Research, University of Bern, Bern, Switzerland, c Department of Radiology, Medical University of Gdansk, Gdansk, Poland, d Department of Nephrology, Hypertension and Clinical Pharmacology, Bern University Hospital, Bern, e CIBM & Department of Radiology, CHUV, Lausanne and f National Centre for Competence in Research (NCCR) Kidney.ch, Zu¨ rich, Switzerland Correspondence to Dr Menno Pruijm, MD, Service of Nephrology and Hypertension, University Hospital Lausanne (CHUV), Rue du Bugnon 17, 1011 Lausanne, Switzer- land. E-mail: menno.pruijm@chuv.ch Received 10 January 2017 Revised 17 March 2017 Accepted 7 April 2017 J Hypertens 35:000–000 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved. DOI:10.1097/HJH.0000000000001406 Journal of Hypertension www.jhypertension.com 1 Original Article Copyright © 2017 Wolters Kluwer Health, Inc. 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