Physiopathogenic Mechanisms Involved in Diabetic Nephropathy, Looking for Prevention and Treatment Solutions
试验速览
- 阶段
- 不适用
- 入组人数
- 10,064
- 试验地点
- 2
- 主要终点
- House localization
研究概览
简要总结
The prevalence of diabetes mellitus (DM) is increasing worldwide, suggesting that 45% of diabetics are undiagnosed. DM induces a kidney disease called diabetic nephropathy (DN) which is the largest single cause of end-stage renal disease and dialysis requirement. In South America the prevalence of DM and chronic kidney disease has increased, and great disparity exists among countries in regards to access to the dialysis treatment. It has been considerate that Hispanic origin increases the risk for DM. The South Americans have distinctive habits, culture, environment, behavior and genetic background and the factors involved in DN have not been defined yet. The early kidney lesions such as neoangiogenesis (pathologic generation of the new blood vessels) and extracellular matrix expansion have been described. The vascular endothelial growth factor A (VEGF) has been linked to angiogenesis, but the role of VEGF in DN has not been elucidated yet. VEGF signals mainly through VEGF receptor 2 (VEGFR2). VEGFR2 interacts with alphaV beta3 integrin (AVB3) in kidney. Additionally tenascin C is expressed in the extracellular matrix. Tenascin C and the tenascin C/AVB3 complex have also been linked to angiogenesis, however their roles have not been unveiled yet in the DN. Investigators hypothesize that VEGF signaling and tenascin C play an important role in DN and that VEGFR2, AVB3 and tenascin C interact. The purposes of this study is to characterize social, environmental and biological factors implicated in the DN in Ecuador and define the role of VEGF signaling and tenascin C in the pathogenesis of the DN. Investigators propose to study factors involved in DN in diabetic and non-diabetic adults from general population, with and without DN. In a single time investigators will evaluate demographics data, habits, personal and family history through a survey. Investigators will measure anthropometrics parameters and blood pressure; investigators will quantify blood glucose, glycosylated hemoglobin A1c and proteinuria. In addition investigators will examine the role of tenascin C and VEGF signaling by analyzing paraffin embedded kidney tissue, plasma and urine samples. Characterizing the factors involved in the DN from Hispanic people is key to establish adequate strategies of prevention, diagnosis and treatment in this population. Furthermore elucidating the role of proteins involved in DN may offer valuable tools for the development of new treatments.
详细描述
- Determinations of social, environmental and biological factor implicated in diabetic nephropathy in Ecuador Investigators will study subjects from the general population. Investigators will contact community and religious leaders in order to invite adult subjects from the general population to participate in this study and 10000 persons will be enrolled.
After teaching basic concepts about prevention of diabetic nephropathy in all subjects, investigators will collect demographics data, house conditions and localization (rural, urban or around the cities), number of people that share a home, education level, employment and economical condition, personal health insurance, medical checkup history, toxic habits (alcohol, cigarette abuse of addictive substances) and physical exercises habits. Investigators will collect personal and family antecedent of diabetes mellitus, diabetic nephropathy, hypertension, kidney diseases, diabetes gestational, current treatments and other chronic diseases. Investigators will measure body weight (Kg), height (m) and investigators will calculate body mass index. Investigators will also measure blood pressure, blood glucose, glycosylated hemoglobin, microalbuminuria and proteinuria. Trained personnel will fill out the person's survey. Investigators will supervise and collect data from 2% of the sample. 2. Role of extracellular matrix proteins and growth factors signaling in diabetic nephropathy
- Systemic and urine studies: proteins involved in diabetic nephropathy pathogenesis as vascular endothelial factor A (VEGF) and extracellular matrix protein as tenascin C (tenascin) concentration will be measured by a commercially available kits in plasma and urine (respectively). Samples will be obtained from diabetics with (n: 20) and without diabetic nephropathy (n: 20) and from non-diabetic subjects (controls) from the general population (n: 2000). Determinations of social, environmental and biological factor will be completed as in aim 1.
- Kidney tissue studies: investigators will determine the role of protein involved in diabetic nephropathy, VEGF signaling and tenascin in:
I) Paraffin embedded kidney tissue obtained from the sample libraries of pathology laboratories will be studied. Slides from non-diabetics (n: 10) and diabetics with diabetic nephropathy (n: 20) and without diabetic nephropathy (n: 10) will be collected. The role of proteins involved in diabetic nephropathy as VEGF signaling and tenascin will be studied by immunohistochemistry and proximity link assay.
II) Paraffin embedded kidney slides from diabetics with diabetic nephropathy (n: 12), non-diabetic control (n: 6) with primary glomerulopathy as minimal change disease, and diabetic controls without diabetic nephropathy (n: 6), will be studied. Investigators will recruit patients with kidney biopsy indicated, and scheduled to be performed, by their medical doctors. After pathology diagnosis completion, some of the remnant paraffin embedded tissue will be used for this study. The role of proteins involved in diabetic nephropathy, VEGF signaling and tenascin will be studied by immunohistochemistry and proximity link assay. Urine and plasma will be collected prior to the kidney biopsy in order to measure protein concentration of potentially useful biomarkers of diabetic nephropathy; VEGF and tenascin levels will be quantified. Patients will be informed and signed consent will be required.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 21 Years 至 70 Years(Adult, Older Adult)
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •age between 21 and 70 years old,
- •persons able to sign informed consent,
- •diabetics without diabetic nephropathy,
- •diabetic with diabetic nephropathy,
- •not hospitalized,
- •not suffering acute disease,
- •living in their home for at least 6 months before to be contacted.
排除标准
- •subjects with acute diseases,
- •subjects with not metabolic compensation,
- •persons temporarily residing in the place of contact,
- •younger than 21 years old,
- •older than 70 years old.
结局指标
主要结局
House localization
时间窗: up to 12 month
House localization (rural, urban or around the cities) in 2000 persons
次要结局
- Protein expression(up to 24 month)
