title: Does statins promote vascular calcification in chronic kidney disease?
abstract: BACKGROUND
  In end-stage renal disease (ESRD), coronary artery calcification (CAC) and inflammation contribute to cardiovascular disease (CVD). Statins do not improve survival in patients with ESRD, and their effect on vascular calcification is unclear. We explored associations between CAC, inflammatory biomarkers, statins and mortality in ESRD.
  
  
  METHODS
  In 240 patients with ESRD (63% males; median age 56 years) from cohorts including 86 recipients of living donor kidney transplant (LD-Rtx), 96 incident dialysis patients and 58 prevalent peritoneal dialysis patients, associations of CAC score (Agatston Units, AUs), interleukin-6 (IL-6) with high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor (TNF), use of statins and all-cause mortality were analysed. Cardiac CT was repeated in 35 patients after 1·5 years of renal replacement therapy. In vitro, human vascular smooth muscle cells (hVSMCs) were used to measure vitamin K metabolism.
  
  
  RESULTS
  Among 240 patients, 129 (53%) had a CAC score > 100 AUs. Multivariate analysis revealed that independent predictors of 1-SD higher CAC score were age, male gender, diabetes and use of statins. The association between CAC score and mortality remained significant after adjustment for age, gender, diabetes, CVD, use of statins, protein-energy wasting and inflammation. Repeated CAC imaging in 35 patients showed that statin therapy was associated with greater progression of CAC. In vitro synthesis of menaquinone-4 by hVSMCs was significantly impaired by statins.
  
  
  CONCLUSIONS
  Elevated CAC score is a mortality risk factor in ESRD independent of inflammation. Future studies should resolve if statins promote vascular calcification and inhibition of vitamin K synthesis in the uremic milieu.
authors.affiliation: Kidney Disease Center, First Affiliated Hospital College of Medicine, Zhejiang University, Hangzhou, China.|Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Abdul Rashid
authors.initials: AR
authors.lastname: Qureshi
authors.affiliation: Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.|Metabolism Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Paolo
authors.initials: P
authors.lastname: Parini
authors.affiliation: Translational Science, CVMD iMed, AstraZeneca R&D, Gothenburg, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Hurt-Camejo
authors.affiliation: Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.|Department of Radiology, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Jonaz
authors.initials: J
authors.lastname: Ripsweden
authors.affiliation: Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.|Department of Radiology, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Torkel B
authors.initials: TB
authors.lastname: Brismar
authors.affiliation: Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Barany
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
authors.forename: Armand M
authors.initials: AM
authors.lastname: Jaminon
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Schurgers
authors.affiliation: Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Heimbürger
authors.affiliation: Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
authors.affiliation: Division of Renal Medicine and Baxter Novum, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D003324:Coronary Artery Disease / Q000139:chemically induced* / Q000401:mortality; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D061205:Vascular Calcification / Q000139:chemically induced* / Q000401:mortality; D014812:Vitamin K / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014812:Vitamin K
keywords: Chronic kidney disease; inflammation; statin; vascular calcification; vitamin K