Renal function and structure in a rat model of arterial calcification and increased pulse pressure.

Abstract

Clinical studies suggest a strong link between tissue calcification and pressure hyperpulsatility in end stage renal disease patients. Using a Wistar rat model of arterial elastocalcinosis and hyperpulsatility [vitamin D and nicotine (VDN) treatment], we evaluated the relative importance of tissue calcification and hyperpulsatility in the etiology of renal failure. VDN rats showed significant increases in aortic wall calcium content (50 times; 992+/-171 vs. control 19+/-1 micromol/g dry wt) and pulse pressure (1.5 times; 61+/-4 vs. control 40+/-2 mmHg). Significant renal calcification (16 times; 124+/-27 vs. control 8.1+/-0.7 micromol/g dry wt) occurred mainly within the media of the preglomerular vasculature and in the areas of interstitial fibrosis in VDN. Extensive renal damages (5 times; 26+/-5% of collapsed-atrophic or sclerotic glomeruli, or glomerular cysts vs. control 5.2+/-0.3%; 28 times; 61+/-12% areas of focal, cortical areas exhibiting interstitial fibrosis per section vs. control 2.2+/-0.6%) were observed histologically. The glomerular filtration rate significantly decreased (880+/-40 vs. control 1,058+/-44 microl.min(-1).g kidney wt(-1)). Albuminuria increased six times (1.6+/-0.4 vs. control 0.27+/-0.04 mg/24 h). There were significant linear relationships between albuminuria and pulse pressure (r2=0.408; n=24) or renal calcium content (r2=0.328; n=24; P<0.05) and between glomerular filtration rate and pulse pressure (r2=0.168; n=27). To our knowledge, this study provides the first evidence of links between both 1) hyperpulsatility and renal dysfunction, and 2) renal calcification and renal dysfunction. Given the increasing frequency of end-stage renal disease, this model could prove useful for preclinical evaluation of drugs that prevent or attenuate hyperpulsatility and/or tissue calcification.

• Authors: Virginie Gaillard, Bernard Jover, Daniel Casellas, Magali Cordaillat, Jeffrey Atkinson, Isabelle Lartaud
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 295 Issue 4 Pg. F1222-9 (Oct 2008) ISSN: 1931-857X [Print] United States
• PMID: 18715942 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium

Topics

• Albuminuria (pathology, physiopathology)
• Animals
• Animals, Outbred Strains
• Aorta (pathology)
• Atrophy
• Blood Pressure (physiology)
• Body Weight
• Calcinosis (pathology, physiopathology)
• Calcium (blood)
• Disease Models, Animal
• Fibrosis
• Glomerulosclerosis, Focal Segmental (pathology, physiopathology)
• Kidney (pathology, physiology)
• Kidney Failure, Chronic (pathology, physiopathology)
• Kidney Glomerulus (pathology, physiopathology)
• Male
• Rats
• Rats, Wistar