Cardiovascular disease in an adenine-induced model of chronic kidney disease: the temporal link between vascular calcification and haemodynamic consequences

J Hypertens. 2013 Jan;31(1):160-8. doi: 10.1097/HJH.0b013e32835b15bb.


Objectives: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / adverse effects
  • Animals
  • Blood Pressure
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / physiopathology
  • Disease Models, Animal
  • Hemodynamics
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Renal Insufficiency, Chronic / chemically induced
  • Renal Insufficiency, Chronic / complications*
  • Risk Factors
  • Vascular Calcification / etiology*
  • Vascular Calcification / physiopathology


  • Adenine