MEDICINA	Patogénesis de la nefropatía diabética
	© M. Carmen Iglesias-de la Cruz, Sheldon Chen, Fuad N. Ziyadeh y Miguel A. Pancorbo-Alonso, 2003  mccruz@iib.uam.es

[RESUMEN]ABSTRACT

Genetic, hemodynamic, and metabolic factors are important in the pathogenesis of diabetic nephropathy. Various mediator factors and signal transduction pathways interact in an intricate circuitry of autocrine, paracrine, or even endocrine mechanisms when the kidney is chronically exposed to high ambient glucose concentrations. The effects of high glucose on renal cells may arise because of increased metabolism of glucose through the polyol pathway, increased de novo synthesis of diacylglycerol with activation of protein kinase C, activation of the hexosamine pathway, or increased nonenzymatic glycation of proteins. Increases in blood pressure, first within glolmerular capillaries and later systemically, and the metabolic consequences of abnormally high glucose levels in renal cells are the components of the most widely accepted concept of how diabetic nephropathy develops and progresses. Both abnormalities induce a maladaptive response in which Transforming Growth Factor-beta (TGF-b) is overproduced and in turn stimulates excessive synthesis of extracellular matrix molecules. Expansion of the glomerular mesangium and tubulointerstitial fibrosis, which are the pathological features of diabetic nephropathy, result from an accumulation of excess matrix.