Urinary dipeptidyl aminopeptidase IV as a marker of early tubular damage in diabetic nephropathy

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The aim of this study was to assess the role of urin ary dipeptidyl aminopeptidase N (DAP IV) in early diabetic nephropathy and impaired glucose tolerance (IGT). We compared urinary DAP N activity, N-acetyl-b-D-glucosaminidase (NAG) activity, and albumin levels between healthy subjects, non-insulin-dependent diabetic (NIDDM) subjects that did not show clinical proteinuria, and IGT subjects. In healthy subjects, a significant difference in the excretion of urinary DAP IV occurred with age. Therefore, we focused mainly on the results of the forties of each group. Urinary DAP IV activity in NIDDM subjects, and IGT subjects was significantly higher than that in controls (1 1.8 ± 5.3,7.2 ±1.4,5.7 ± 0.8 U/g creatinine (Cr), respectively, p <0.0 0 1). No statistically significant difference in urinary NAG activity was observed compared with controls (NIDDM; 4.5 ± 2.7, IGT; 3.7 ± 1.7, control; 2.9 ± 1.2 U/g Cr). A significant correlation was observed between urinary DAP N and urinary NAG in NIDDM and IGT groups. In both groups, some subjects showed elevated DAP N activity despite normal NAG activity, while no subjects showed both normal DAP IV activity and higher NAG activity. Urinary albumin levels in NIDDM subjects also were higher than those in controls (p < 0.0 1), but this difference was less pronounced than that for DAP IV activity (p < 0.0 0 1). We conclude that measurement of urinary DAP N activity is a useful tool for detecting early diabetic nephropathy.