AORTIC CALCIFICATION IN ADENINE-INDUCED RAT MODELS OF CHRONIC KIDNEY DISEASE

Mr Sean A Barton¹, Miss  Ozer S¹, Miss  Hicks AJ¹, Miss  Belikoff H, A/Prof  Hildreth CM¹, Prof  Phillips JK¹

¹Department of Biomedical Sciences Macquarie University, Macquarie Park, Australia

Aim: To characterise aortic vascular calcification (VC) in adenine-induced chronic kidney disease (CKD) in two different rat strains.

Background: Aortic VC is a common complication of CKD and established independent risk factor for cardiovascular disease. VC causes arterial stiffness, placing end organs at risk of pulsatile damage. Animal models of VC are required to elucidate the pathology driving VC in CKD and develop novel therapeutic strategies.

Methods: Mixed-sex (6-week-old) Lewis (n=8) rats were given 0.4% adenine supplemented feed to age 18-weeks, while mixed-sex (6-week-old) Wistar (n=8) were treated with 0.25% adenine to age 10-weeks and then 0.4% to age 18-weeks. Control animals of each strain were given normal feed. At 18-weeks, systolic-blood-pressure (SBP) was determined (tail-cuff plethysmography) and the animals were euthanised. Plasma, aorta, and kidney were collected. Plasma urea and creatinine was assayed. Aortic calcium content (AC) was measured (o-cresolphthalein) and H&E-stained kidney sections prepared.

Results: Adenine treatment increased plasma urea (Lewis: 34.9±9.9 vs 7.2±0.1 mM; P<0.05, Wistar: 78.9±16.0 vs 7.1±0.3 mM; P<0.01), being significantly greater in the Wistar (P<0.05), and creatinine (Lewis: 160.5±39.4 µM vs. 24.0±6.3 µM; P<0.01, Wistar: 303.3±57.3 µM vs. 17.0±1.7 µM; P<0.01). AC was increased in the Wistar (11.3±1.9 vs. 5.7±0.2 µmol/g dwt; P<0.05) but not Lewis (5.3±0.4 vs. 4.6±0.3 µmol/g dwt). SBP was not changed in either strain (Lewis: 102.5±3.6 vs. 105.7±4.5 mmHg, Wistar: 127.1±11.7 vs 125.9±4.1 mmHg). H&E kidney sections of adenine-treated rats displayed substantial crystal deposits and tubular-dilations.

Conclusions: Strain is a consideration in model development as adenine induced renal function decline was substantially worse in the Wistar, and only the Wistar developed VC, noting neither strain showed an increase in SBP.

Biography:

I am a research assistant at Macquarie University, with interest and experience in basic biomedical research of chronic kidney diseases and hypertension.