Adipokine zinc-alpha-2-glycoprotein as a novel urinary biomarker presents earlier than microalbuminuria in diabetic nephropathy

Abstract

Objective: To investigate the role of zinc-alpha-2-glycoprotein (ZAG) in the early stage of diabetic nephropathy, in patients with type 2 diabetes mellitus (T2DM).

Methods: This cross-sectional observational study recruited patients with longstanding T2DM and healthy control subjects. Patients with T2DM were further stratified based on their urine albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Serum and urine concentrations of ZAG were determined using an enzyme-linked immunosorbent assay.

Results: Eighty patients with T2DM and 20 healthy control subjects were enrolled in the study. Mean ± SD concentrations of ZAG in serum and urine were both significantly higher in patients with T2DM (serum: 38.29 ± 22.72 mg/l; urine: 53.64 ± 29.48 mg/g) compared with concentrations in healthy control subjects (serum: 21.61 ± 8.83 mg/l; urine: 28.17 ± 10.64 mg/g). Serum ZAG concentration was positively correlated with serum creatinine and eGFR. Urine ZAG concentration was positively correlated with UACR. Urine concentration of ZAG in the higher eGFR group was higher than that in the normal eGFR group (41.26 ± 13.67 versus 32.05 ± 8.55 mg/g, respectively).

Conclusion: These preliminary findings suggest that ZAG might be a potentially useful biomarker for early diagnosis of diabetic nephropathy in patients with T2DM.

Keywords: Zinc-alpha-2-glycoprotein; albuminuria; biomarker; diabetic nephropathy.

Figure 1.

Spearman’s rank correlation coefficient analysis of the association between urine zinc-alpha-2-glycoprotein (ZAG) concentration and urine albumin–creatinine ratio (UACR) in patients with type 2 diabetes mellitus (n = 80) who participated in this study to determine the role of ZAG in the early diagnosis of diabetic nephropathy. r = 0.824, P < 0.01.

Figure 2.

Urine zinc-alpha-2-glycoprotein (ZAG) concentrations in patients with type 2 diabetes mellitus (n = 80), stratified according to urine albumin–creatinine ratio (UACR) into a normal albuminuria group (UACR < 30 mg/g, n = 40), microalbuminuria group (30 mg/g ≤ UACR < 300 mg/g, n = 20), and macroalbuminuria group (UACR ≥ 300 mg/g, n = 20), compared with healthy control subjects (n = 20). Data presented as mean ± SD. *P < 0.01 compared with healthy control group; one-way analysis of variance.

Figure 3.

Urine zinc-alpha-2-glycoprotein (ZAG) concentrations in patients with type 2 diabetes mellitus in a normal albuminuria group (n = 40), stratified according to estimated glomerular filtration rate (eGFR) into a normal eGFR group (eGFR < 120 ml/min per 1.73 m², n = 20) and a higher eGFR group (eGFR ≥ 120 ml/min per 1.73 m², n = 20) compared with healthy control subjects (n = 20). Data presented as mean ± SD. *P < 0.05 compared with normal eGFR group; one-way analysis of variance.