Polycystic Kidneys Have Decreased Vascular Density: A Micro‐CT Study

Abstract

Objective Polycystic kidney disease (PKD) is a common cause of end stage renal failure and many of these patients suffer vascular dysfunction and hypertension. It remains unclear whether PKD is associated with abnormal microvascular structure. Thus, this study examined the renovascular structure in PKD. Methods PKD rats (PCK model) and controls were studied at 10 weeks of age, and mean arterial pressure (MAP), renal blood flow and creatinine clearance were measured. Microvascular architecture and cyst number and volume were assessed using micro-computed tomography, and angiogenic pathways evaluated. Results Compared to controls, PKD animals had an increase in MAP (126.4±4.0 vs. 126.2±2.7mmHg) and decreased clearance of creatinine (0.39±0.09 vs. 0.30±0.05ml/min), associated with a decrease in microvascular density, both in the cortex (256±22 vs. 136±20 vessels per cm2) and medullar (114±14 vs. 50±9 vessels/cm2) and an increase in the average diameter of glomeruli (104.14±2.94 vs. 125.76±9.06 mm). PKD animals had increased fibrosis (2.2±0.2 fold vs. control) and a decrease in the cortical expression in hypoxia inducible factor 1-α and vascular endothelial growth factor. Conclusion PKD animals have impaired renal vascular architecture, which can have significant functional consequences. The PKD microvasculature could represent a therapeutic target to decrease the impact of this disease.

Determinants of renal tissue hypoxia in a rat model of polycystic kidney disease

“…This finding might seem surprising, since oxygen that diffuses into the cyst fluid must come from the wall itself. However, corrosion casts of the renal vasculature of humans with autosomal dominant PKD revealed the presence of a dense network of (albeit abnormal) capillaries surrounding the cyst wall (3, 52) despite a decreased total density of blood vessels within the polycystic kidney (54). The presence of these "vascular capsules" may even be an important mechanism facilitating the growth and proliferation of cysts (52).…”

Mesenchymal Stromal Cells Improve Renovascular Function in Polycystic Kidney Disease

“…Creatinine levels in blood and urine as well as proteinuria was measured as previously described (48). …”

“…As previously described, the cortex was divided into outer and inner regions, and the outer medulla into an outer and inner strip (23,48). The spatial density of cortical microvessels (diameters <200 µm) was calculated in each cross-section.…”

Image-based modelling of skeletal muscle oxygenation

“…In order to enhance X-ray absorption, it can be coated with a material of high atomic number, such as osmium tetroxide [79]. Microfil (Flow Tech Inc., USA) is a frequently used silicone rubber; a polymer that is fluid during perfusion and hardens within 30 min [71,82,[92][93][94][95][96][97]. A problem often encountered with this agent is that it does not always perfuse all of the microvasculature [96].…”

“…mCT has been used in many studies on vascular networks; some examples include imaging of the ocular and renal microvasculature [69][70][71], imaging of scaffold -bone interaction [72], phenotyping of cardiovascular development in mouse embryos [73], imaging of remodelled bioactive glass foam scaffolds [74], functional imaging of rat hearts [75], studying cavernous haemangioma of the liver [76], examining neovascularization in tissue-engineered bone constructs [77] or computer-aided design of microvasculature [78,79]. Heinzer et al [80] used a combination of both mCT and SR CT to perform a multi-scale analysis of vascular networks.…”