Diabetic Nephropathy: An Inherited Disease or Just a Diabetic Complication?

Type 2 diabetic nephropathy is the most common cause of end-stage renal disease in western Europe and the United States. Although patients with overt nephropathy generally experience greater cumulative glycemic exposure, the difference in glycemic control between patients developing nephropathy and to those who did not could not be demonstrated. This observation is consistent with the finding that factors other than glycemic control are involved in the development of nephropathy. Genetic factors which specifically increase the susceptibility to nephropathy in patients with diabetes have been proposed. A range of linkage, association, and gene expression studies have been performed for revealing the genetic background of diabetic nephropathy but were not yet successful in identifying mutations which could explain the development of diabetic nephropathy in the majority of diabetic patients. Because of relatively small case numbers of all studies being performed so far, conclusions from those studies are limited. With the development of better technologies for an affordable genomewide association study using thousands of markers, it might become possible to unravel the genetic susceptibility factors for diabetic nephropathy. Comparing the expression levels of thousands of genes in patients and controls may identify key players in the pathogenesis of diabetic nephropathy and targets for pharmacologic intervention in the future.