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

Abstract

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.

Poly (ADP-Ribose) Polymerase as a Potential Target for the Treatment of Acute Renal Injury Caused by Lipopolysaccharide

“…[30] Increased urinary NAG excretion is one of the most sensitive markers of renal disease and suggests that the cell injury is in the renal proximal tubules. [30][31][32] This was also supported by renal histological changes in LPS-treated animals.…”

Urinary biomarkers of diabetic nephropathy

“…43,44 Increased urinary levels of retinol-binding protein have been found in a pediatric population of type 1 DM patients with and without microalbuminuria, signifying that this marker may be used to detect early tubular damage. 45 In a recent prospective study that followed type 2 DM patients for an average of 30 months, urinary retinol-binding protein appeared to be an independent predictor of disease progression (risk of dialysis, doubling of serum creatinine or death) after adjusting for confounding factors such as creatinine clearance, proteinuria, and blood pressure. 12 Monocyte chemoattractant protein-1 is a secreted chemokine that is thought to play an important role in the pathogenesis of tubulointerstitial disease by activating macrophage recruitment in diabetic nephropathy.…”

The use of lysosomal enzymuria in the early detection and monitoring of the progression of diabetic nephropathy

“…Urinary excretion of smaller molecular weight proteins such as N-acetyl-E-D-glucosaminidase (NAG) and retinol binding protein (RBP) indicate proximal tubular dysfunction, and may identify diabetic patients at risk of developing diabetic nephropathy (29). In a trial to assess renal tubular function, Salema et al (29) found that diabetic patients with microalbuminuria had concomitant renal tubular disorder indicated by high urinary NAG and RBP.…”

“…In a trial to assess renal tubular function, Salema et al (29) found that diabetic patients with microalbuminuria had concomitant renal tubular disorder indicated by high urinary NAG and RBP. Meanwhile, patients without microalbuminuria had both tubular markers excreted in urine in significantly higher amounts than controls.…”