title: The Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study: objectives, design, and methodology.
abstract: OBJECTIVE
  Children and adolescents with chronic kidney disease (CKD) are at high risk for cardiovascular morbidity and mortality. A systemic arteriopathy and cardiomyopathy has been characterized in pediatric dialysis patients by the presence of morphologic and functional abnormalities.
  
  
  METHODS
  The Cardiovascular Comorbidity in Children with CKD (4C) Study is a multicenter, prospective, observational study aiming to recruit more than 600 children, aged 6 to 17 years, with initial GFR of 10 to 45 ml/min per 1.73 m(2). The prevalence, degree, and progression of cardiovascular comorbidity as well as its association with CKD progression will be explored through longitudinal follow-up. The morphology and function of the heart and large arteries will be monitored by sensitive noninvasive methods and compared with aged-matched healthy controls. Multiple clinical, anthropometric, biochemical, and pharmacologic risk factors will be monitored prospectively and related to the cardiovascular status. A whole-genome association study will be performed to identify common genetic variants associated with progression of cardiovascular alterations and/or renal failure. Monitoring will be continued as patients reach end-stage renal disease and undergo different renal replacement therapies.
  
  
  RESULTS
  While cardiovascular morbidity in adults is related to older age and additional risk factor load (e.g., diabetes), the role of CKD-specific factors in the initiation and progression of cardiac and vascular disease are likely to be characterized with greater sensitivity in the pediatric age group.
  
  
  CONCLUSIONS
  The 4C study is expected to provide innovative insight into cardiovascular and renal disease progression in CKD.
authors.affiliation: Department of Pediatric Nephrology, Charité Universitätsmedizin Berlin CVK, Augustenburger Platz 1, 13353 Berlin, Germany. uwe.querfeld@charite.de
authors.forename: Uwe
authors.initials: U
authors.lastname: Querfeld
authors.forename: Ali
authors.initials: A
authors.lastname: Anarat
authors.forename: Aysun K
authors.initials: AK
authors.lastname: Bayazit
authors.forename: Aysin S
authors.initials: AS
authors.lastname: Bakkaloglu
authors.forename: Yelda
authors.initials: Y
authors.lastname: Bilginer
authors.forename: Salim
authors.initials: S
authors.lastname: Caliskan
authors.forename: Mahmut
authors.initials: M
authors.lastname: Civilibal
authors.forename: Anke
authors.initials: A
authors.lastname: Doyon
authors.forename: Ali
authors.initials: A
authors.lastname: Duzova
authors.forename: Daniela
authors.initials: D
authors.lastname: Kracht
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Litwin
authors.forename: Anette
authors.initials: A
authors.lastname: Melk
authors.forename: Sevgi
authors.initials: S
authors.lastname: Mir
authors.forename: Betül
authors.initials: B
authors.lastname: Sözeri
authors.forename: Rukshana
authors.initials: R
authors.lastname: Shroff
authors.forename: René
authors.initials: R
authors.lastname: Zeller
authors.forename: Elke
authors.initials: E
authors.lastname: Wühl
authors.forename: Franz
authors.initials: F
authors.lastname: Schaefer
mesh_terms: D000293:Adolescent; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002908:Chronic Disease; D015897:Comorbidity; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology; D011379:Prognosis; D011446:Prospective Studies; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors