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 with controls, PKD animals had an increase in MAP (126.4 ± 4.0 vs. 126.2 ± 2.7 mmHg) and decreased clearance of creatinine (0.39 ± 0.09 vs. 0.30 ± 0.05 mL/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.

Conclusions: 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.

Figure 1

General characteristics of control and PCK animals. Compared to controls, 10 weeks old PCK rats had increased renal volume (A), with 9.7±1.6% of the entire kidney occupied by cysts (B). PCK animals had a small but significant increase in mean arterial pressure (C) and a decrease in renal perfusion (D), with impaired glomerular function, as assessed by clearance of creatinine (E) and proteinuria (F). *p<0.05 vs. control.

Figure 2

Top, representative 3D images of kidneys from control (A) and PCK (B) animals, showing a decreased density of cortical microvessels in PCK animals. Samples were scanned with micro-CT, reconstructed and displayed at a resolution of 17 μm cubic voxel resolution. Bottom, representative 3D images of cortical renal vasculature of control (C) and PCK (D) animals displayed at 17 μm resolution, demonstrating segmental irregularities in PKD vasculature.

Figure 3

Histological and protein expression analysis of kidneys from controls and PCK animals. A and B showed Hematoxolin & Eosin staining of kidneys from control and PCK rats showing cystic structures in PCK (3B) and not in control (3A). Furthermore, Picrosirius red staining for fibrosis demonstrates increased fibrosis in both the cortex and medulla in PCK rats (3D and 3F, respectively) compared to control (3C and 3E, respectively), quantified in 3G. H–K shows cortical protein expression, densitometry and quantitation normalized to β-actin, of angiogenic factors, showing decreased expression of hypoxia inducible factor (HIF) 1-α and vascular endothelial growth factor (VEGF) pathways. * p<0.05 compared to control. VEGFR-1: VEGF receptor-1.