尿铜蓝蛋白、肾损伤因子1与糖尿病肾病患者肾功能的关系及对预后不良的预测价值研究

摘要 目的：探讨尿铜蓝蛋白（CP）、肾损伤因子1（KIM-1）与糖尿病肾病（DKD）患者肾功能的关系及对预后不良的预测价值。方法：回顾性分析2017年1月～2019年1月陆军第八十二集团军医院肾内科收治的160例DKD患者（DKD组）的临床资料，随访3年，根据是否发展为终末期肾脏疾病（ESRD）分为预后不良组42例和预后良好组118例，另选取同期56例单纯2型糖尿病（T2DM）患者作为T2DM组和47例体检健康者作为对照组。采用微量法和酶联免疫吸附试验法检测尿CP、KIM-1水平，并计算尿白蛋白/肌酐比值（UACR）和估算肾小球滤过率（eGFR）。通过Spearman相关性分析DKD患者尿CP、KIM-1与UACR、eGFR的相关性，单因素和多因素Logistic回归分析DKD患者预后不良的影响因素，受试者工作特征（ROC）曲线分析尿CP、KIM-1对DKD患者预后不良的预测价值。结果：随访3年，160例DKD患者有42例发展为ESRD，预后不良发生率为26.25％（42/160）。DKD组尿CP、KIM-1、UACR高于T2DM组、对照组，eGFR低于T2DM组、对照组（P＜0.05）；T2DM组尿CP、KIM-1、UACR高于对照组，eGFR低于对照组（P＜0.05）。Spearman相关性分析显示，DKD患者尿CP、KIM-1与UACR呈正相关（P均＜0.001），与eGFR呈负相关（P均＜0.001）。多因素Logistic回归分析显示，高血压、DKD分期4期和糖化血红蛋白（HbA1c）（较高）、低密度脂蛋白胆固醇（LDL-C）（较高）、UACR（较高）、尿CP（较高）、尿KIM-1（较高）为DKD患者预后不良的独立危险因素（P＜0.05），eGFR（较高）为独立保护因素（P＜0.05）。ROC曲线分析显示，尿CP、KIM-1联合预测DKD患者预后不良的曲线下面积大于各指标单独预测。结论：DKD患者尿CP、KIM-1升高与肾功能降低和预后不良密切相关，尿CP、KIM-1联合预测DKD患者预后不良的价值较高。

Injury Molecule-1 and Renal Function in Patients with Diabetic Kidney Disease and Their Predictive Value for Poor Prognosis

ABSTRACT Objective: To investigate the relationship between urinary ceruloplasmin (CP) and kidney injury molecule-1 (KIM-1) and renal function in patients with diabetic kidney disease (DKD) and their predictive value for poor prognosis. Methods: The clinical data of 160 patients with DKD who were admitted to Department of Nephrology, Army 82nd Group Military Hospital from January 2017 to January 2019(DKD group) were retrospectively analyzed, and they were followed up for 3 years, according to whether they developed end-stage renal disease(ESRD), they were divided into poor prognosis group with 42 cases and good prognosis group with 118 cases. And another 56 patients with pure type 2 diabetes mellitus(T2DM) in the same period were selected as the T2DM group and 47 healthy individuals on physical examination as the control group. Urinary CP and KIM-1 levels were measured by microscopic method and enzyme-linked immunosorbent assay, and urinary albumin to creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were calculated. Spearman correlation was used to analyze the correlation between urinary CP and KIM-1 and UACR and eGFR in patients with DKD. Univariate and multivariate Logistic regression were used to analyze the influencing factors of poor prognosis in patients with DKD. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of urinary CP and KIM-1 for poor prognosis in patients with DKD. Results: After 3 years of follow-up, 42 cases of 160 patients with DKD developed ESRD, and the incidence of poor prognosis was 26.25% (42/160). Urinary CP, KIM-1 and UACR in the DKD group were higher than those in the T2DM group and control group, and eGFR was lower than that in the T2DM group and control group(P<0.05). Urinary CP, KIM-1 and UACR in the T2DM group were higher than those in the control group, and eGFR was lower than that in the control group (P<0.05). Spearman correlation analysis showed that urinary CP and KIM-1 were positively correlated with UACR(all P<0.001), and negatively correlated with eGFR (all P<0.001). Multivariate Logistic regression analysis showed that hypertension, DKD stage 4, glycosylated hemoglobin (HbA1c) (higher), low-density lipoprotein cholesterol (LDL-C) (higher), UACR (higher), CP (higher), KIM-1 (higher) were independent risk factors for poor prognosis in patients with DKD(P<0.05), the eGFR (higher) was an independent protective factor(P<0.05). ROC curve analysis showed that the area under curve of urinary CP and KIM-1 in predicting poor prognosis of patients with DKD was greater than that of each indicator alone. Conclusion: Elevated urinary CP and KIM-1 in patients with DKD are closely associated with reduced renal function and poor prognosis, and the combination of urinary CP and KIM-1 has a high value in predicting the poor prognosis of patients with DKD.