Arterial Function In Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease(ADPKD) is one of the most common human hereditary kidney diseases with a prevalence of 1/400-1/1000, estimated to affect more than 1.5 million people and account for about 5% of end stage renal disease patients requiring renal replacement therapy in China. The disease is characterized by the progressive formation of multiple renal cysts affecting all segments of the renal tubules and about 50% patients develop renal insufficiency in the fifth and sixth decades of life. However, at present the unclearness of pathogenesis and pathophysiology of ADPKD results in no effective treatment to this disease. Therefore, the development of ADPKD and its complications remains the focus.Cardiovascular diseases are one of the earlier and more common complications of ADPKD, and also one of its main causes of death. Renin-angiotensin-aldosterone system (RAAS) plays a role in target organ injuries such as atherosclerosis, left ventricular hypertrophy, heart failure and renal failure. RAAS activation starts at early stage of ADPKD, so arteries injury may occur before clinical menifestation appearance. Early diagnosis and intervention may be benefit to postpone the development of cardiovascular complications.The purpose of our research is observing the arterial changes in animal model and patients of ADPKD, in order to offerring evidence to assess the risk factor of cardiovascular disease in ADPKD.This study consists of 2 sections:1. We observed the pathology of thoracic aorta in Han:SPRD rat with difference phenotype and age. The subject included 45 male heterozygous, female heterozygous (Cy / +) and normal (+ / +) SPRD rats ( 4, 8, 12 weeks old). The blood pressure and renal function were measured, and then the rats were killed , descending aorta was obmined to observe the pathomorphological changes with haematine-eosin staining , and the distribution of the expression of intercellular adhesion molecule-1(ICAM-1) was observed with immunohistochemical staining.It was found that there were distinct changes in male heterozygous rats of 8 and 12 weeks old under light microscope, and the expression of ICAM-1 increased in endothelial cell of male heterozygous rats. The extent of damage in endothelium related to severity of disease. With the aggravation of endothelium injury, the renal function damage and hypertension gradually developed. whereas the endothelial injury in female rats whose diseases were not serious. Moreover, the expression of ICAM-1 in 4-week-old male rats increased significantly when its renal function and blood pressure still remained normal.2. We observed the morphologic, mechanical and functional sonographic parameters of arteties in ADPKD patients with normal renal function. Thirty-two hypertensive and 28 normotensive patients with ADPKD with preserved renal function, 25 patients with essential hypertension, and 30 healthy subjects were included in the study. By means of high-resolution vascular ultrasound, brachial artery endothelial dependent vasodilation (EDV), carotid intima-media thickness (IMT) and distensibility were measured. It is founded that EDV was significant worse in hypertensive patients with ADPKD compared with patients with essential hypertension and normotensive patients with ADPKD, and even in normotensive patients with ADPKD compared with healthy subjects. Carotid IMT was significant greater in both hypertensive and normotensive patients with ADPKD compared with healthy subjects. Moreover, carotid cross-sectional distensibility (CD) and incremental elastic modulus (Einc) differed significantly between both hypertensive and normotensive patients with ADPKD and healthy subjects.It proved that The endothelium injury of Han:SPRD rat might occurred when renal function and blood pressure were nomal. Both hypertensive and normotensive patients with ADPKD show significant endothelial dysfunction, increased IMT and decreased distensibility, which are predictors of artery injury The endothelium injury might occurred when renal function and blood pressure were nomal. Therefore, it is important for prevention cardiovascular disease in ADPKD to monitor arterial function and control it development and advancement.