Mechanisms of Diabetic Nephropathy in Ecuador

Plain-language summary

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.

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