Diabetic nephropathy (DN) is a progressive kidney disease caused by thickening of the capillaries in the kidney glomeruli. People with both types I and type II diabetes are at risk. The risk is higher if blood-glucose levels are poorly controlled. Furthermore, once nephropathy develops, the greatest rate of progression is seen in patients with poor control of their blood pressure.
Diabetic nephropathy is the most common cause of chronic kidney failure and end-stage kidney disease in the United States and worldwide (1,2). In the U.S., diabetic nephropathy accounts for about 40% of new cases of ESRD (3). About 20–30% of patients with type I or type II diabetes develop evidence of nephropathy, but in type II diabetes, a considerably smaller fraction of these progresses to ESRD. However, because of the much greater prevalence of type II diabetes, such patients constitute over half of those diabetic patients currently starting on dialysis.
The goals of treatment of diabetic nephropathy are to slow the progression of kidney damage and control related complications. Different therapeutic strategies targeting diabetic nephropathy have been explored such as tight glycemic control (4), tight blood pressure control (5), and various inhibitors of the renin angiotensin aldosterone system (RAAS) (6-8). While these therapies appear to slow the progression of kidney disease due to diabetes, none of them are curative. Dialysis may be necessary once end-stage renal disease develops. At this stage, a kidney transplant must be considered. Another option for type 1 diabetes patients is a combined kidney-pancreas transplant.
Recent evidence has emerged in the last decade to suggest uric acid has several reported effects by which it may cause diabetic nephropathy; including endothelial dysfunction, increased activity of the renin-angiotensin system, induction of inflammatory cascades, and pro-fibrososis cytokine activation, all of which have been demonstrated to contribute to progression of micro-vascular disease and thereby renal injury in diabetic nephropathy (9). Evidence from three observational studies in patients with diabetes have generated a substantial body of evidence that serum uric acid levels are strong determinants of the development of diabetic nephropathy and the loss of kidney function among individuals with diabetes, both Type 1 and Type 2 (10,11,12). In addition, two randomized controlled trials in patients with CKD and/or diabetic nephropathy demonstrated allopurinol significantly improved kidney function (13, 14).
As the total number of people with type I and II diabetes is predicted to rise dramatically the prevalence of diabetic nephropathy is also expected to increase dramatically. Current treatments appear to slow the progression of kidney disease due to diabetes, none of them are curative. Pharmacologic therapy focused on treatment of hyperuricemia may provide a new and effective approach for the treatment of DN.