The Expression of Angiopoietin-2 in Diabetic Nephropathy and Correlated with Proteinuria
|School||Huazhong University of Science and Technology|
|Keywords||diabetic nephropathy Angiopoietin-2 IL-18 urinary albumin excretion rate|
AIMS: To investigate whether angiopoietin-2 level can be clinical target for early diagnosis and therapy in diabetic nephropathy ,we tested the change of serum、urine and kidney tissue angiopoietin-2 and IL-18 level in type 2 diabetes and different phases of DN, and elucidated the correlation between angiopoietin-2 and other biochemical assays, such as IL-18、serum creatinine、proteinuria and so on.METHODS: Thirty-five Chinese patients with type 2 diabetes were enrolled. According to their UAER diabetic patients were divided into three groups randomly:①normoalbuminuric diabetic group(DM1,n=11), UAER was less than 20μg/min, mean age 52.6yrs;②microalbuminuric diabetic group(DM2,n=11), UAER was 20 to 200μg/min, mean age 51.9 yrs;③proteinuric diabetic group(DM3,n=13), UAER was more than 200μg/min, mean age 57yrs. In addition 7 healthy controls(NC) were enrolled, mean age 49 yrs. The patients’basic information were recorded, such as age、sex、BMI、serum creatinine、microalbuminuric concentration of 24 hours、urinary NAG、urinary RBP、urinary ALB、urinary IgG. UAER was calculated from the formula. Serum and urinary Angiopoietin-2 and IL-18 were measured by Enzyme-linked immunosorbent assay technology (ELISA). To observe the expression of Ang-2 in diabetic nephropathy, immunohistochemical staining was performed from renal punch biopsy compared with normal kidney tissues.RESULTS:①The level of serum Ang-2 increased in DM1 compared with NC, and serum Ang-2 levels in DM2 and DM3 were much higher. There was statistics difference among four groups (P<0.05). Urinary Ang-2 increased in DM1 compared with NC. Urinary Ang-2 levels in DM2 and DM3 were much higher. There was statistics difference among four groups (P<0.05).②Up-regulated Ang-2 protein expression was present in glomeruli alongside of the capillary loops in patients with DN compared with control.③Serum Ang-2 had significant positive correlation with urinary Ang-2、UAER、serum creatinine、urinary RBP、urinary ALB and urinary IgG. Urinary Ang-2 had significant positive correlation with serum creatinine、UAER、urinary RBP、urinary ALB and urinary IgG.④Compared with NC, the level of serum IL-18 in DM1 had the trend to ascend, but there was no statistics difference(P﹥0.05). Serum IL-18 in DM2 was much higher compared with NC and DM1 groups and there was significant difference (P<0.05). Serum IL-18 in DM3 was higher compared with DM2, but there was no statistics difference(P﹥0.05). The level of urinary IL-18 in DM2 and DM3 were much higher compared with NC and DM1 groups (P<0.05). Urinary IL-18 in DM3 had the trend to ascend compared with DM2, but there was no statistics difference(P﹥0.05).⑤Serum IL-18 had significant positive correlation with urinary IL-18、serum creatinine、UAER、urinary ALB and urinary IgG. There was weak positive correlation of serum IL-18 with urinary RBP. Urinary IL-18 had significant positive correlation with UAER、urinary ALB and urinary IgG. There was weak positive correlation of urinary IL-18 with serum creatinine and urinary RBP.⑥Serum and urinary Ang-2 had significant positive correlation with serum IL-18 and urinary IL-18.CONCLUSION: The expression of Ang-2 was up-regulated in diabetic nephropathy. Urinary Ang-2 had positive correlation with UAER and IL-18, and was significantly higher in normoalbuminuric stage. It was more sensitive than UAER and was closely related with DN. So urinary Ang-2 can be used as an indicator of early diagnosis and therapy of DN.