Targets to retard the progression of diabetic nephropathy.

By the year 2025, the World Heath Organization estimates that over 300 million people worldwide will have diabetes [1]. Over 5% of newly diagnosed patients with type 2 diabetes will already have diabetic kidney disease and a further 30% to 40% will develop diabetic nephropathy, mostly within 10 years of diagnosis [2]. In patients with type 1 diabetes, 25% to 40% will develop diabetic nephropathy [3]. Although the proportion of patients with type 1 diabetes developing nephropathy has reduced markedly over the past 20 years in Western countries [4], the increasing incidence and survival of patients with type 1 diabetes means that the absolute numbers of patients with type 1 diabetes and diabetic nephropathy may continue to rise. By contrast, the incidence of both type 2 diabetes and diabetic nephropathy in these patients has risen steadily over the last 50 years [3]. These facts, in combination with the improved survival from cardiovascular comorbidity, mean that diabetic nephropathy has now become the single most common cause of end stage renal disease (ESRD) in the Western world, with over half of all patients on renal replacement programs now having diabetes [5]. This figure significantly underestimates the actual burden of diabetic renal disease, as the high mortality rate from cardiovascular disease limits the full expression of diabetic nephropathy. Future improvements in cardiovascular survival will see the natural history of diabetic nephropathy played out in increasing numbers of patients. This has already been seen in patients with type 1 diabetes. For example, in 1971, the median survival of patients with type 1 diabetes and overt nephropathy was 5 years, with fewer than 10% surviving more than 10 years [6]. Consequently, few patients were able to stay the course of their renal disease. By comparison, in 1996, the median survival in an equivalent population was over 17 years [5]. Not surprisingly, nearly ten times more patients with type 1 diabetes are now entering ESRD programs. In this context, this article reviews both basic and clinical