The onset of renal damage in diabetes mellitus may be influenced by several factors which largely result from genetic predisposition, hereditary factors and the early appearance of microalbuminuria and/or systemic hypertension. Most of these factors are also implicated in the progression of nephropathy from microalbuminuria to overt proteinuria and to end-stage renal failure (ESRF). Over the last few years, the role of hyperglycaemia has emerged as critical in mediating the progressive renal damage in diabetes. However, hyperglycaemia leads to increased formation of glycated proteins which may act as promoters of progression by localizing in renal tissue. In addition, hyperglycaemia may have a synergistic effect with some other risk factors, such as growth factors and the renin angiotensin system, in accelerating renal deterioration.