Urinary Measurement of Transforming Growth Factor-[Beta] and Type Iv Collagen As New Markers of Renal Injury: Application in Diabetic Nephropathy (Enzymes and Protein Markers‪)‬

Measurement of total urinary protein in individuals testing positive by urinary dipstick is a typical method for assessing the presence of potentially serious glomerular disorders. In the absence of such overt proteinuria however, measurement of specific urinary proteins such as [[beta].sub.2] microglobulin or myeloma proteins may be useful in the diagnosis of tubulopathies or overflow proteinuria, whereas subclinical albumin hyperexcretion may serve as useful early predictor of diabetic nephropathy (1-5). Sequential monitoring of such markers serves as a guide to progressive renal injury or as a means of gauging the influence of intervention measures on the disease process. Recent experimental studies suggest that newer urinary markers may serve as early indicators of renal injury and may provide greater insight into the pathogenesis of progressive glomerulosclerosis. With this objective we developed methods to measure urinary transforming growth factor-[beta]1 (TGF-[beta]1) [3] and type III collagen (T3C) as markers of extracellular matrix synthesis or remodeling (6-15), and retinol-binding protein (RBP) as a sensitive and reliable indicator of tubular injury or dysfunction (1, 16,17). Because diabetic nephropathy has been characterized by different stages of albumin excretion rates (AERs), ranging from normoalbuminuria, microalbuminuria (AER 20 200 Ag/min), or macroalbuminuria (AER 200 [micro]g/min) (2-5), which correspond to increasing histopathologic severity (18), this disorder was selected to test the clinical utility of such novel urinary markers. Materials and Methods