Urinary excretion of n-acetyl-β-d-glucosaminidase and retinol binding protein as alternative indicators of nephropathy in patients with type 1 diabetes mellitus

Diabetic nephropathy (DN) is usually characterized by glomerular dysfunction, with microalbuminuria as an early indicator. Urinary excretion of smaller molecular weight proteins such as n-acetyl-beta-glucosaminidase (beta-NAG) and retinol binding protein (RBP) indicate proximal tubular dysfunction, and may identify diabetic patients at risk of developing diabetic nephropathy. In a trial to assess renal tubular function, urinary excretion of beta-NAG (by colorimetric assay) and RBP (by ELISA) were determined in 59 type 1 diabetic patients (mean age 15 +/- 3.2 yr). Of the 59 patients, 11 were microalbuminuric while 48 had normal urinary albumin excretion (UAE). Patients were compared with 40 matched healthy subjects. Diabetic patients with microalbuminuria (n = 11) had concomitant renal tubular disorder indicated by high urinary beta-NAG in all (100%) and RBP in 10 (90.9%) of them. Meanwhile, patients without microalbuminuria (n = 48) had both tubular markers excreted in urine in significantly higher amounts than controls (mean beta-NAG = 6.88 vs. 3.76 U/g Cr, p < 0.001; RBP = 386.6 vs. 151.8 microg/dL, p < 0.001). Among those patients, 29 (61%) had raised urinary beta-NAG activity, and 39 (82%) had increased loss of RBP in urine. A significant correlation was found between urinary beta-NAG and RBP in normoalbuminuric patients (r = 0.66, p < 0.001), as well as between each of the two tubular markers and HbA1c (r = 0.83, p < 0.001). At 30 and 36 months of follow-up, two out of 48 (4.2%) diabetic patients developed persistent microalbuminuria. Both had elevated baseline HbA1C, and urinary beta-NAG. In conclusion, proximal tubular dysfunction may occur independent of glomerular alteration. Whether tubular markers precede the development of microalbuminuria needs further study.