糖尿病肾病患者血清HMGA2蛋白表达及其与肾功能进展的关系

目的 探讨糖尿病肾病（DN）患者血清高迁移率族蛋白A2 (HMGA2)的表达及其与肾功能进展的关系。方法 选取2016年10月-2017年8月内分泌科经肾脏穿刺活检确诊的DN患者159例，根据肾功能进展的终点将DN患者分为肾功能进展组(n=61)和肾功能未进展组(n=98)。检测患者血清HMGA2蛋白的表达水平，分析其与临床病理资料的相关性，Logistic回归分析探讨DN患者肾功能进展的危险因素。受试者工作特征曲线（ROC）评价血清HMGA2水平对DN患者肾功能进展的评估价值。 结果 肾功能进展组收缩压、血肌酐、尿素氮、24小时尿蛋白定量、血尿酸、HMGA2水平、间质小管及血管评分高于非肾功能进展组，肾小球滤过率（eGFR）、血清白蛋白水平低于非肾功能进展组，差异具有统计学意义（P<0.05）。DN患者的血清HMGA2水平与血肌酐、尿素氮、间质小管及血管评分呈正相关（P<0.05），与eGFR呈负相关（P<0.05）。高龄、高水平的基线血肌酐、24小时尿蛋白定量、HMGA2以及低水平的基线eGFR和血清白蛋白是DN患者肾功能进展的独立危险因素(OR>1, P<0.05) 。HMGA2具有较高的对肾功能进展的评估价值，ROC-AUC为0.760(0.663～0.872)。 结论 DN肾功能进展的患者血清HMGA2表达水平升高，且与患者基线肾功能以及肾小管间质和血管病变程度密切相关。血清HMGA2表达水平较高的DN患者肾功能进展较快，肾脏预后较差。

The relationship between the expression of serum HMGA2 protein and the progression of renal function in diabetic nephropathy

Abstract: Objective　To investigate the relationship between the serum expression of high mobility group protein A2 (HMGA2) and the decreased renal function in patient with diabetic nephropathy (DN). Methods　A total of 159 DN patients who were diagnosed by renal biopsy in our hospital were selected. According to the decline in renal function, DN patients were divided into rapid renal function decline group (61 cases) and non-rapid renal function decline group (98 cases). The results of laboratory examination and the expression level of serum HMGA2 were compared between the two groups, and its correlation with clinicopathological data was analyzed. Logistic regression analysis was used to explore the risk factors of renal function decline in DN patients. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of serum HMGA2 level in the renal function decline of DN. Results　The systolic blood pressure, serum creatinine, urea nitrogen, 24 h urinary protein, serum uric acid, HMGA2 levels, interstitial tubule scores and vascular scores were higher in the rapid renal function decline group than those in the non-rapid renal function decline group. The glomerular filtration rate (eGFR) and serum albumin level were lower in the rapid renal function decline group than those of non-rapid renal function decline group (all P＜0.05). The serum HMGA2 levels were positively correlated with serum creatinine (r=0.464) in DN patients, urea nitrogen (r=0.323), 24 h urinary protein (r=0.261), interstitial tubule score and vascular score (r=0.497), and negatively correlated with EGFR (r=-0.344) and hemoglobin (r=-0.199), (P＜0.05). The advanced age, high level of serum creatinine, 24 h urinary protein, HMGA2, low level of eGFR and serum albumin were independent risk factors for renal function decline in DN patients. HMGA2 showed a high evaluation value for renal function decline, and ROC-curve AUC was 0.760 (95% CI:0.663-0.872). The cutoff value was 1.5 μg/L, the sensitivity and specificity were 0.772 and 0.745 respectively. Conclusion　The level of serum HMGA2 expressionis increased in DN patients with renal function decline, which is closely related to the baseline renal function and the degree of tubulointerstitial and vascular lesions.