title: Cardiovascular disease in an adenine-induced model of chronic kidney disease:  the temporal link between vascular calcification and haemodynamic consequences.
abstract: OBJECTIVE
  Medial vascular calcification is highly prevalent in chronic kidney disease (CKD), and it is a risk factor for mortality. This study characterizes the time course and the link between calcification of major arteries, changes in blood pressure (BP) and cardiac growth in experimental CKD.
  
  
  METHODS
  CKD (elevated serum creatinine and urea) was induced with a 0.25% adenine diet (5, 8 and 11 weeks). BP was measured by radiotelemetry in conscious rats or indwelling catheter under anaesthesia. At each time point, serum biochemistry and tissue calcification was quantified.
  
  
  RESULTS
  CKD was present in all animals by 5 weeks and the ensuing 6 weeks (11 weeks total). CKD animals developed elevated serum phosphate (5-8 weeks) and fibroblast growth factor-23 (FGF-23; 5-11 weeks) levels. There was a 100% incidence of calcification at 11 weeks, 71% at 8 weeks and 33% at 5 weeks, and distal arteries appeared more susceptible than proximal arteries. Calcification was associated with widening of pulse pressure (PP), and a higher pulse wave. Continuous radiotelemetry revealed a significant increase in SBP variability and an accelerated (<24 h) elevation in PP of at least 10 mmHg following 8 weeks of CKD. This precipitous change was driven by a drop in mean DBP rather than elevated mean SBP. PP, duration of CKD and FGF-23 levels correlated with left ventricular hypertrophy.
  
  
  CONCLUSIONS
  The unique haemodynamic consequences of medial calcification, combined with the hormonal consequences of hyperphosphatemia (i.e. FGF-23), seem to have an exacerbated risk for left ventricular hypertrophy.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Navid
authors.initials: N
authors.lastname: Shobeiri
authors.forename: Judy
authors.initials: J
authors.lastname: Pang
authors.forename: Michael A
authors.initials: MA
authors.lastname: Adams
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Holden
mesh_terms: D000225:Adenine / Q000009:adverse effects; D000818:Animals; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D006439:Hemodynamics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000150:complications*; D012307:Risk Factors; D061205:Vascular Calcification / Q000209:etiology* / Q000503:physiopathology
chemical_list: D000225:Adenine