The presence of microalbuminuria in patients with diabetes mellitus is associated with a marked increased risk of cardiovascular mortality and progression to end-stage kidney disease. Currently, there are no markers that predict which patients with diabetes will develop microalbuminuria. Based on our work examining the mechanisms of glomerular and tubular injury we have postulated that a urinary marker will precede the onset of diabetic microalbuminuria and will thus provide a very early indication of those patients who are at risk of developing diabetic nephropathy and cardiovascular events. The specific goals for the phase 1 studies are as follows: I) To establish a semi-automated assay to process a larger number of samples than is possible to do manually. II) Human studies: A) to establish normal values of the urinary marker in the general population without renal disease. B) 1. to determine the point prevalence of type 2 diabetic patients without microalbuminuria but positive urinary marker, and 2. to measure the urinary marker in type 2 diabetic patients without microalbuminuria and prospectively determining the risk of developing microalbuminuria in these patients. These phase 1 proof of concept and feasibility studies will also lay the groundwork for more definitive studies related to predictive value as well as future preventive therapies with agents targeted toward a causative mechanism. ? ?
