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 μmol/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 μmol/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 μl·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.