Effects of uric acid on endothelial dysfunction in early chronic kidney disease and its mechanisms

Yu Wang, Xiaorong Bao, Yu Wang, Xiaorong Bao

Abstract

Background: An increase in serum uric acid (UA) occurs during the early and middle stages of chronic kidney disease (CKD) and aggravates the deterioration of kidney function. This study aims to explore the relation between UA and endothelial dysfunction in early CKD and its mechanisms in a murine model.

Methods: The experimental animals were randomly divided into three groups (n = 10): sham-operation group (control group), right nephrectomy only group (CKD group) and right nephrectomy with oxonic potassium group (CKD with hyperuricemia group). Furthermore, we analyzed the relation between UA and endothelial dysfunction indices in early CKD as well as its mechanisms.

Results: Linear regression analysis showed that the level of serum UA had a significant positive correlation with serum endothelin-1 and the percentage of collagen I positive area, but a negative correlation with serum nitric oxide (NO) and NO/endothelin-1 ratio. In addition, the level of serum UA had significant positive correlations with serum malonaldehyde, serum C-reactive protein, serum oxidatively-modified low-density lipoprotein and serum low-density lipoprotein, but a negative correlation with serum superoxide dismutase.

Conclusions: Endothelial dysfunction in the CKD group was significant and had a positive correlation with the level of serum UA. Endothelial dysfunction in early CKD with hyperuricemia is perhaps related to oxidative stress, micro-inflammation and lipid oxidation.

Figures

Figure 1
Figure 1
Pathological pictures of rat kidneys from groups A, B, and C. (A) The normal renal glomerulus of group A (×400). (B) No obvious pathological change in renal tubules of group A (×400). (C, E) Mild glomerular mesangial proliferation in renal glomerulus of groups B and C (×400). (D, F) There were no obvious pathological changes in renal tubules in groups B and C (×400).
Figure 2
Figure 2
Pathological images of rat arteries from groups A, B, and C. (A) Endothelial cells arranged in order under the vascular intima of group A (×400). (B) There was no obvious proliferation of medial smooth muscle cells in the vascular wall of group A (×200). (C) The morphology of endothelial cells of group B was slightly abnormal (×400). (D) There was no obvious proliferation of medial smooth muscle cells in the vascular wall of group B (×200). (E) Endothelial cells of group C had a foam-like change (×400). (F) Endothelial cells of group C shed from the vessel wall (×400). (G, H) Inflammatory cells accumulated in the vascular intima of group C (×400). (I) Neutrophil granulocytes were seen around the endothelial cells of group C (×400). (J) Mononuclear cells were seen around the endothelial cells of group C (×400). (K) Smooth muscle cells of group C proliferated, thickened, and had no order (×200).
Figure 3
Figure 3
Collagen I staining of the vascular wall in groups A, B, and C. (A,B) A small amount of collagen I deposition was seen in the vascular wall of group A (×400). (C) Collagen I component was significantly increased in group C (×400).

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