Mechanisms of Renal Microvascular Dysfunction in Type 1 Diabetes: Potential Contribution to End Organ Damage

The mechanisms underlying initiation and progression of diabetic nephropathy are not well understood, despite the fact that diabetes represents the chief underlying cause of end-stage renal disease. The onset of diabetic hyperglycemia is now known to evoke functional alterations in the renal microvasculature, glomeruli and tubular epithelium. Although the scope of these effects is not yet fully recognized, the renal vascular dysfunction evident early after onset of T1D likely encompasses impaired electromechanical coupling in preglomerular vascular smooth muscle and altered interactions between tubular transport and vascular function. These changes, which arise in environment conducive to oxidative stress and inflammation, are thought to either initiate or facilitate the eventual development of diabetic nephropathy in susceptible individuals.