Research On The Correlation Between Diabetic Nephropathy And The Levels Of Urinary Alpha-actinin-4in Type2Diabeties Mellitus Patients

Objective:This study was done to evaluate the expression of a-actinin-4in the type2diabetes mellitus (T2DM) patients urine, and analyze the association between the renal injury and the levels of urinary α-actinin-4.Method:Type2diabetic patients (n=124) with normoalbuminuria group (urinary albumin<30mg/24h,n=60), microalbuminuria group ((30≤urinary albumin <300)mg/24h,n=32)、macroalbuminuria group (urinary albumin≥300mg/24h,n=32)、normal control group (n=30) were enrolled. All objects are collected the general information such as sex, age, course of disease, etc; measuring blood pressure, weight, height, body mass index. The levels of urinary a-actinin-4were measured by using ELISA kits, and serum/urine creatinine, serum urea nitrogen, cystatin C, blood glucose, glycated hemoglobin, C-peptide and other clinical indicators were measured by conventional methods.The eGFR level was calculated using the formula proposed by Hojs R。 Data analysis by the statistics software SPSS13.0, and comparison of the rate were analysed by the chi-square,Comparisons among three or more parameters were analysed by one-way analysis of variance, eliminate confounding factors use covariance analysis; comparisons between two parameters were analysed by Student’s unpaired t-test. The relationships between a-actinin-4expression and clinical parameters were analysed by spearman correlation analysis、partial correlation analysis and multiple regression analysis. The relationships between urinary a-actinin-4and the kidney function in the in the type2diabetes mellitus patients were analysed by the binary logistic regression analyses. P value<0.05was considered statistically significant.Results:The levels of urinary a-actinin-4in the T2DM group were significantly higher than those in the normal control group and increased gradually with albuminuric levels. The a-actinin-4level in the T2DM macroalbuminuria group was highest, the T2DM microalbuminuria group was the second, while the T2DM microalbuminuria group was lowest, the difference was statistically significant (P<0.05). According to the course of diabetes mellitus, the patients in the normoalbuminuria group are divided into two groups:the course of diabetes mellitus less than5years and more than5years group. We found that the levels of urinary a-actinin-4in the the course of more than5years group is higher than that in less than five years group despite a similar degree of albuminuria, the difference was statistically significant (P<0.05). The α-actinin-4level in urine was found to statistically positive correlate with the course of diabetes mellitus(r=0.433, P<0.05)、serum urea nitrogen(r=0.419, P<0.05), creatinine (r=0.316, P<0.05), cystatin C (r=0.472, P<0.05),24h-urinary albumin (r=0.553, P<0.05)、fasting plasma glucose (FPG)(r=0.304, P<0.05) and2-hour postchallenge glucose (PG2h)(r=0.373, P<0.05),and negative correlate with eGFR (r=-0.456, P<0.05). Eliminating the the impact of blood glucose and the course of diabetes mellitus, there was a statistically significant positive correlation between urinary a-actinin-4and serum urea nitrogen (r=0.394, P<0.05). creatinine (r=0.243, P<0.05), cystatin C (r=0.343, P<0.05),24h-urinary albumin (r=0.437,P<0.05). and a significant negative correlation between urinary a-actinin-4and eGFR (r=-0.372, P<0.05). Multiple regression analysis showed that both the course of diabetes mellitus and fasting plasma glucose are risk factors of the high urinary level of a-actinin-4(Adjusted R2=0.347, P<0.05).Logistic regression analysis shows an association between urinary a-actinin-4and renal dysfunction (OR=1.481;95%CI,1.187-1.847)Conclusion:Urine level of α-actinin-4is closely related to with diabetic nephropathy,and α-actinin-4may participates in the progress of diabetic nephropathy; urinary α-actinin-4can reflect the early renal injury and be associated with renal function. Both the course of diabetes mellitus and fasting plasma glucose are risk factors of the high urinary level of α-actinin-4. The high urinary level of α-actinin-4was identified as one of high-risk factors associated with T2DM patients with renal dysfunction.Urinary α-actinin-4needs to be investigated as a potential marker for diabetic nephropathy early diagnosis and indicator of curative effect.