糖尿病肾病患者尿液基质金属蛋白酶组织抑制剂2、胰岛素样生长因子结合蛋白7的水平及其临床意义

Levels and clinical significance of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 in patients with diabetic nephropathy

  • 摘要:
    目的 探讨糖尿病肾病(DN)患者尿液基质金属蛋白酶组织抑制剂2(TIMP-2)、胰岛素样生长因子结合蛋白7(IGFBP7)水平及其临床意义。
    方法 选取254例DN患者为研究组, 另选取同期230例单纯2型糖尿病患者为对照组,比较2组患者临床资料。根据估算肾小球滤过率(eGFR)将DN患者分为Ⅰ期组32例, Ⅱ期组84例, Ⅲ期组90例, Ⅳ期组48例; 根据血清肌酐及尿量将DN患者分为AKI组19例和非AKI组235例; 比较血清肌酐、尿液TIMP-2、IGFBP7水平在不同组别患者中的差异。采用酶联免疫吸附法检测尿液TIMP-2、IGFBP7水平及尿肌酐水平; 采用Pearson检验分析尿液TIMP-2、IGFBP7与相关指标的关系; 采用受试者工作特征(ROC)曲线评价尿液TIMP-2、IGFBP7及血清肌酐诊断DN患者发生AKI的效能。
    结果 研究组血清肌酐、糖化血红蛋白(HbA1c)、血尿酸、尿素氮、尿微量白蛋白、24 h尿蛋白定量、尿β2-微球蛋白水平均高于对照组,血清白蛋白、eGFR水平均低于对照组,差异有统计学意义(P < 0.05)。Ⅲ期、Ⅳ期DN患者血清肌酐、尿TIMP-2与尿肌酐的比值(TIMP-2/尿肌酐)、尿IGFBP7与尿肌酐的比值(IGFBP7/尿肌酐)均高于Ⅰ期、Ⅱ期患者,差异有统计学意义(P < 0.05); 与非AKI组相比, AKI组患者血清肌酐、尿TIMP-2/尿肌酐、尿IGFBP7/尿肌酐均升高,差异有统计学意义(P < 0.05)。尿液TIMP-2、IGFBP7与血清肌酐、HbA1c、血尿酸、尿素氮、尿微量白蛋白、24 h尿蛋白定量、尿β2-微球蛋白均呈正相关(P < 0.05), 与血清白蛋白、eGFR均呈负相关(P < 0.05)。ROC曲线显示,尿液TIMP-2、IGFBP7、血清肌酐预测DN患者发生AKI的曲线下面积(AUC)分别为0.676(95%CI: 0.587~0.756)、0.864(95%CI: 0.792~0.918)、0.618(95%CI: 0.528~0.703), 尿液TIMP-2联合IGFBP7预测DN患者发生AKI的AUC为0.926(95%CI: 0.866~0.965)。
    结论 DN患者尿液TIMP-2、IGFBP7水平随病情加重而呈上升趋势,对DN患者发生AKI有一定的预测价值。

     

    Abstract:
    Objective To explore the levels and clinical significance of urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) in patients with diabetic nephropathy (DN).
    Methods A total of 254 DN patients were selected as study group, 230 patients with simple type 2 diabetes in the same period were selected as control group, and the clinical materials were compared between the two groups. According to the estimate glomerular filtration rate (eGFR), DN patients were divided into stage I group (n=32), stage Ⅱ group (n=84), stage Ⅲ group (n=90) and stage Ⅳ group (n=48); according to serum creatinine level and urinary volume, the DN patients were divided into AKI group (n=19) and non-AKI group (n=235); the differences in levels of serum creatinine, urinary TIMP-2 and IGFBP7 in different groups were compared. The levels of urinary TIMP-2, IGFBP7 and urinary creatinine were detected by enzyme-linked immunosorbent assay; Pearson test was used to analyze the relationships of urinary TIMP-2 and IGFBP7 with related indicators; receiver operating characteristic (ROC) curve was used to evaluate the efficiency of urinary TIMP-2, IGFBP7 and serum creatinine in diagnosing AKI in DN patients.
    Results The levels of serum creatinine, glycosylated hemoglobin (HbA1c), blood uric acid, urea nitrogen, urinary microalbumin, 24-hour urinary protein quantitation and urinary β2-microglobulin in the study group were significantly higher than those in the control group, while the levels of serum albumin and eGFR were significantly lower than those in the control group (P < 0.05). The levels of serum creatinine, urinary TIMP-2 to urinary creatinine ratio (TIMP-2/urinary creatinine) and urinary IGFBP7 to urinary creatinine ratio (IGFBP7/urinary creatinine) in DN patients in stage Ⅲ and Ⅳ were significantly higher than those in patients in stage Ⅰand Ⅱ(P < 0.05); compared with the non-AKI group, the levels of serum creatinine, urinary TIMP-2/urinary creatinine and urinary IGFBP7/urinary creatinine were significantly higher in the AKI group (P < 0.05). Urinary TIMP-2 and IGFBP7 were positively correlated with serum creatinine, HbA1c, blood uric acid, urea nitrogen, urinary microalbumin, 24-h urinary protein quantitation and urinary β2-microglobulin (P < 0.05), but were negatively correlated with serum albumin and eGFR (P < 0.05). ROC curve showed that the areas under the curve (AUC) of urinary TIMP-2, IGFBP7 and serum creatinine in predicting incidence of AKI in DN patients were 0.676 (95%CI, 0.587 to 0.756), 0.864 (95%CI, 0.792 to 0.918), 0.618 (95%CI, 0.528 to 0.703) respectively, and the AUC of urinary TIMP-2 combined with IGFBP7 in predicting incidence of AKI in DN patients was 0.926 (95%CI, 0.866 to 0.965).
    Conclusion The levels of urinary TIMP-2 and IGFBP7 in DN patients increase with the aggravation of the disease, which have a certain predictive value for AKI in DN patients.

     

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