title: Urinary enzyme measurements as early indicators of renal insult in type 2 diabetes.
abstract: The association between urine microalbumin, alpha1-microglobulin concentration (alpha1MG) and the urinary enzyme activities of alanine aminopeptidase (AAP), N-acetyl-beta-D-glucosaminidase (NAG), alpha-glutathione-S-transferase (alphaGST) and pi-glutathione-S-transferase (piGST) is investigated in 36 type 2 diabetic and 15 age- and sex-matched non-diabetic subjects. Diabetic subjects were grouped into those with microalbuminuria <3 mg/L (group A: 7M/5F), 3-30 mg/L (group B: 5M/7F) and 30-300 mg/L (group C: 6M/6F). While serum creatinine concentration remained within the laboratory reference range (<115 mmol/L) in all experimental groups, alpha1MG excretion increased with the severity of microalbuminuria (control group and groups A, B and C mean [SD] values were 1.3 [0.21], 1.6 [0.11], 2.18 [0.42] and 2.8 [0.51] mg/mmol urinary creatinine, respectively). Activities of NAG (U/mmol creatinine) were significantly elevated in groups A, B and C at 98.7 (8.6), 112.8 (12.9) and 147.4(16.2), respectively, compared with the reference range <35 U/mmol creatinine (group C vs. groups A and B: P < 0.01). Activity of AAP (U/mmol creatinine) was significantly elevated in groups B and C at 7.6 (0.5) and 7.9 (0.6), respectively (both P < 0.001), compared to the control and group A values (2.5 [0.2]). Activity of piGST (U/mmol creatinine) was elevated in groups B and C at 2.6 (0.4) and 2.8 (0.5), respectively (both P < 0.001), compared to the control and group A values (1.1 [0.1]). Similarly, urine piGST activity was also elevated in groups B and C at 2.9 (0.6) and 3.1 (0.5), respectively (both P < 0.001), compared to control and group A values (1.3 [0.1] and 1.4 [0.2]). These results suggests that site-specific urinary biochemical markers provide valuable information about early renal proximal and distal tubular insult that ultimately may precede enhanced glomerular permeability in subjects with type 2 diabetes.
authors.affiliation: School of Allied Health Sciences, De Montfort University, Leicester LE1 9BH, UK.
authors.forename: A
authors.initials: A
authors.lastname: Kalansooriya
authors.forename: P
authors.initials: P
authors.lastname: Jennings
authors.forename: F
authors.initials: F
authors.lastname: Haddad
authors.forename: I
authors.initials: I
authors.lastname: Holbrook
authors.forename: P H
authors.initials: PH
authors.lastname: Whiting
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000652:urine*; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000652:urine; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests
chemical_list: D015415:Biomarkers; D005982:Glutathione Transferase