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.
Subject(s)
Diabetic Nephropathies/metabolism , Vascular Endothelial Growth Factor A/physiology , Angiopoietins/physiology , Diabetic Nephropathies/epidemiology , Diabetic Nephropathies/pathology , Diabetic Nephropathies/physiopathology , Global Health , Humans , Insulin Resistance , Kidney Glomerulus/metabolism , Kidney Glomerulus/pathology , Membrane Proteins/physiology , Nitric Oxide/physiology , Nitric Oxide Synthase Type III/physiology , Receptor, Insulin/physiology , Receptors, Vascular Endothelial Growth Factor/physiology , Signal TransductionABSTRACT
La prevalencia de diabetes mellitus aumentó en el último siglo y se estima que el 45%de los pacientes, no estarían diagnosticados. En Sudamérica la prevalencia de diabetes y de enfermedad renal crónica (ERC) incrementó, existiendo gran disparidad entre los países respecto al acceso a diálisis. En Ecuador es una de las principales causas de mortalidad, principalmente en las provincias ubicadas en la costa del océano Pacífico. La mayor causa aislada de ingreso a diálisis es la nefropatía diabética (ND). Aun utilizando las mejores opciones terapéuticas para la ND, el riesgo residual de proteinuria y de ERC terminal permanece elevado. En esta revisión describimos la importancia del problema en el mundo y en nuestra región Analizamos estudios moleculares y celulares relevantes que indican la crucial importancia de eventos glomerulares en el desarrollo y en la evolución de la ND y en la insulinorresistencia. Incluimos conceptos anatómicos, fisiopatológicos y clínicos básicos, desarrollando especial énfasis en el rol de factores angiogénicos como el factor de crecimiento vascular endotelial(VEGF-A) y su relación con el receptor de insulina, la sintasa endotelial de óxido nítrico-óxidonítrico (eNOS) y las angiopoietinas. En el transcurso del texto proponemos diversas vías, que a nuestro entender tienen potencial terapéutico. Profundizar en el estudio del VEGF-A y la sangiopoietinas, el estado de VEGF resistencia glomerular, la relación del receptor 2 de VEGF/nefrina, VEGF/receptores de insulina/nefrina, la relación VEGF/eNOS-ON a nivel glomerular podría aportar soluciones al acuciante problema de la ND en el mundo y generar nuevas alternativas de tratamiento (AU)
The prevalence of diabetes mellitus increased during the last century and it is estimated that45% 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 (AU)
