Aspectos celulares y moleculares de la nefropatía diabética, rol del VEGF-A

Abstract

The prevalence of diabetes mellitus increased during the last century and it is estimated that 45% of the patients are not diagnosed. In South America the prevalence of diabetes and chronic kidney disease (CKD) increased, with a great disparity among the countries with respect to access to dialysis. In Ecuador it is one of the main causes of mortality, principally in the provinces located on the coast of the Pacific Ocean. The greatest single cause of beginning dialysis is diabetic nephropathy (DN). Even using the best therapeutic options for DN, the residual risk of proteinuria and of terminal CKD remains high. In this review we indicate the importance of the problem globally and in our region. We analyse relevant cellular and molecular studies that illustrate the crucial significance of glomerular events in DN development and evolution and in insulin resistance. We include basic anatomical, pathophysiological and clinical concepts, with special attention to the role of angiogenic factors such as the vascular endothelial growth factor (VEGF-A) and their relationship to the insulin receptor, endothelial isoform of nitric oxide synthase (eNOS) and angiopoietins. We also propose various pathways that have therapeutic potential in our opinion. Greater in-depth study of VEGF-A and angiopoietins, the state of glomerular VEGF resistance, the relationship of VEGF receptor 2/nephrin, VEGF/insulin receptors/nephrin and the relationship of VEGF/eNOS-NO at glomerular level could provide solutions to the pressing world problem of DN and generate new treatment alternatives.

Identification of miRNAs-genes regulatory network in diabetic nephropathy based on bioinformatics analysis

“…The up- and downregulation of the podocyte VEGFA levels during renal development led to glomerular disease. [34] This study identified that VEGFA was a key gene that was downregulated in DN, consistent with previous studies. Sivaskandarajah et al [35] found that selective knockout of VEGFA in glomerular podocytes of diabetic mice resulted in a significant increase in proteinuria with severe glomerular scar formation and increased apoptosis.…”

Association of Chemerin and Vascular Endothelial Growth Factor (VEGF) with Diabetic Nephropathy

“…Chemerin participates in inflammation, obesity, and insulin resistance by regulating glucolipid metabolism and promoting adipocyte differentiation [ 12 ]. Vascular endothelial growth factor (VEGF) can stimulate vascular endothelial cell division and enhance vascular endothelial cell permeability, thus promoting vascular endothelial cell proliferation, differentiation, and angiogenesis [ 13 , 14 ]. However, the correlation of Chemerin and VEGF with DN has not been fully elucidated.…”

Comportamiento diferencial del paciente diabético en relación al no diabético en Hemodiálisis, en el hospital provincial de Camagüey, Cuba

“…Quienes la padecen presentan un alto riesgo de desarrollar nefropatía diabética y entre el 20 y el 50 % de ellos tiene riesgo de sufrir insuficiencia renal crónica terminal (IRCT) y necesitar de diálisis o trasplante de riñones [1][2][3] . Se sabe que cerca del 40 % de los casos nuevos de IRCT se debe a esta patología.…”

“…En consecuencia, se estima que la prevalencia mundial de DM tipo 2 aumentará, de los 171 millones que había en el año 2000, a una cifra de, al menos, 366 millones para el año 2030. Por tanto, un mayor número de personas llegará a padecer IRCT y requerir terapia renal sustitutiva 6,8 . Las así llamadas "complicaciones microvasculares" (retinopatía y nefropatía) son responsables directas de la morbilidad más frecuentemente asociada a la DM.…”

“…Si, además de lo anterior, consideramos que la esperanza de vida del diabético es, en promedio, ocho años menor que la de personas no diabéticas en edades de 55 a 64 años y cuatro años menor en los de 65 a 74 7 , podemos ratificar que esta afección constituye, cada vez más, un importante problema de salud 7,8 . Por causa del envejecimiento de la población mundial, hacia el 2025, padecerán diabetes 146 millones de personas entre los 40 y los 59 años y 147 millones de personas con 60 años o más 11 .…”