Prognosis of diabetic nephropathy: how to improve the outcome.

Chronic renal diseases, including diabetic nephropathy, evolve to terminal renal failure by a process leading to progressive parenchimal damage which appears relatively independent of the initial insult. When glomerular permselectivity is lost, proteins filtered through the glomerular capillary, through proximal tubular cell activation and up-regulation of genes of inflammatory and vasoactive mediators, may give rise to an inflammatory reaction that in the long-term can contribute to renal scarring. If this interpretation is correct, the best approach to try to retard the progression of several renal diseases would be to limit the excessive traffic of macromolecules throughout the glomerular capillary by molecules, as the angiotensin-converting-enzyme (ACE) inhibitors, that may help restore perm-selective properties to normal. Thus, the present review addresses the mechanism(s) of the renal protective effect of ACE inhibitors and analyzes the evidence so far available of their salutary effect in human nephropathies, with particular focus on diabetic nephropathy. The issue of whether ACE inhibitors alone or in combination with other antihypertensives (namely non-dihydropyridinic calcium channel blockers) may even prevent the onset of nephropathy at the stage of normoalbuminuria is discussed.