URINARY MEASUREMENT OF TRANSFORMING-GROWTH-FACTOR-BETA AND TYPE-IV COLLAGEN AS NEW MARKERS OF RENAL INJURY - APPLICATION IN DIABETIC NEPHROPATHY

Urinary samples were concentrated rapidly and efficiently and were use d to develop several protein assays that may be of value in monitoring individuals with progressive renal disorders. Transforming growth fac tor-beta 1 (TGF-beta 1) and retinol binding protein (RBP) were measure d with modification of commercially available methods used to assay se rum specimens; type 3 collagen (T3C) was measured with a new immunonep helometric assay. The precision characteristics of these assays are co mparable with those reported for microalbuminuria. The clinical utilit y of measuring a panel of these markers was demonstrated in urine samp les from 16 control subjects and from 46 individuals with insulin-depe ndent diabetes mellitus (IDDM) with various albumin excretion rates (A ERs). TGF-beta 1 and T3C were used as markers of cytokine expression a nd of the renal fibrogenic process, whereas REP excretion served as a marker of tubular injury or dysfunction. Compared with controls, T3C e xcretion was significantly increased in 18 normoalbuminuric and furthe r increased in 13 microalbuminuric (AER 20 less than or equal to 200 m u g/min) IDDM subjects. REP excretion was increased in macroalbuminuri c IDDM subjects (AER >200 mu g/min, overt nephropathy). Significant co rrelations were also found between AER and REP in all but macroalbumin uric individuals, whereas TGF-beta 1 correlated with T3C excretion in controls and in normoalbuminuric diabetic subjects. Urinary REP but no t AER was an excellent predictor of diabetic nephropathy as defined by serum creatinine (P = 0.0001). This underscores the importance of an early tubulopathy in the subsequent development of glomerulopathy and overt nephropathy. The data suggest that longitudinal monitoring of a panel of urinary markers such as that used in the current study may be tter define their relevance in progressive glomerulosclerosis and may also provide greater insight into the mechanisms underlying such proce ss.