尿铁调素与2型糖尿病肾病的关系及其临床意义
Relationship between urinary hepcidin and type 2 diabetic nephropathy and its clinical significance
目的:分析尿液中铁调素在不同分期2型糖尿病肾病(diabetic kidney disease,DKD)患者中的表达水平及其与DKD及相关指标的关系。方法:选择上海健康医学院附属周浦医院2022年6月至2023年12月内分泌科住院2型糖尿病患者139例为研究对象。DKD分期通过尿微量白蛋白/尿肌酐比值(urinary albumin/creatinine ratio,UACR)判定:A1期为UACR<30 mg/g,A2期DKD为UACR≥30 mg/g~≤300 mg/g,A3期DKD为UACR>300 mg/g。按照DKD分期进行分组,其中A1期患者50例(A1组),A2期DKD患者47例(A2组),A3期DKD患者42例(A3组)。采用酶联免疫吸附测定法测定尿铁调素,同时检测空腹血糖、总胆固醇、甘油三酯、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、血肌酐及糖化血红蛋白(hemoglobin A1c,HbA1c)并进行比较,分析尿铁调素与其他指标的相关性、DKD风险因素及诊断价值的评价。呈正态分布的计量资料以 xˉ± s表示,3组间均数比较,若方差齐性,采用方差分析检验;若方差不齐,采用韦尔奇检验;计数资料组间构成比或率采用 χ2检验;相关性分析采用Pearson相关性分析;多因素分析采用二元Logistic回归模型;采用受试者特征曲线分析尿铁调素在诊断DKD中的价值。 结果:A1组尿铁调素为(5.3±1.0)μg/L,A2组为(7.7±2.5)μg/L,A3组为(10.1±2.7)μg/L,3组间差异有统计学意义( F=58.92, P<0.001),并且随DKD严重程度增加而增高;尿铁调素与UACR( r=0.684, P<0.001)、血肌酐( r=0.590, P<0.001)、病程( r=0.485, P<0.001)、甘油三酯( r=0.264, P=0.002)、年龄( r=0.235, P=0.005)、总胆固醇( r=0.224, P=0.008)及收缩压( r=0.194, P=0.022)呈正相关,与肾小球滤过率( r=-0.540, P<0.001)、BMI( r=-0.175, P=0.040)呈负相关;与空腹血糖、HbA1c、ALT及舒张压无相关性(均 P>0.05)。其次,通过二元Logistic回归分析提示尿铁调素水平的升高是DKD发生的风险因素( OR=4.147,95% CI:2.154~7.984, P<0.001)。通过受试者特征曲线分析显示尿铁调素最佳诊断切点为6.35 μg/L,此时敏感度为0.831,特异度为0.880。 结论:尿铁调素随DKD严重程度而升高,可能成为DKD早期诊断的生物学标志物。
更多Objective:To analyze the expression level of hepcidin in urine of patients with type 2 diabetic kidney disease (DKD) in different stages and its relationship with DKD and related indicators.Methods:From June 2022 to December 2023, 139 inpatients with type 2 diabetes mellitus in the Department of Endocrinology, Zhoupu Hospital Affiliated to Shanghai Health Medical College were selected as the research objects. The stage of DKD was judged by urinary albumin/creatinine ratio (UACR): UACR <30 mg/g in stage A1, UACR ≥30 mg/g~≤300 mg/g in stage A2. DKD in stage A3 was UACR >300 mg/g. According to the stage of DKD, there were 50 patients with stage A1 (group A1), 47 patients with stage A2 (group A2), and 42 patients with stage A3 (group A3). Urinary hepcidin was determined by enzyme-linked immunosorbent assay, and fasting blood glucose, total cholesterol, triglyceride, alanine aminotransferase (ALT), serum creatinine and hemoglobin A1c (HbA1c) were measured and compared. The correlation between urinary hepcidin and other markers, the risk factors of DKD and the evaluation of diagnostic value were analyzed. Measurement data with normal distribution were expressed as xˉ± s, mean comparison among the three groups, if the variance was homogeneous, the analysis of variance test was used; if the variance was not homogeneous, the Welch test was used; the proportion or rate of enumeration data among the groups was tested by χ2 test; Pearson correlation analysis was used for correlation analysis; binary Logistic regression model was used for multivariate analysis; The value of urinary hepcidin in the diagnosis of DKD was analyzed by receiver operating characteristic curve. Results:Urinary hepcidin was (5.3±1.0) μg/L in group A1, (7.7±2.5) μg/L in group A2, and (10.1±2.7) μg/L in group A3. There was significant difference among the three groups ( F=58.92, P<0.001), and urinary hepcidin increased with the severity of DKD; Urinary Hepcidin was related to UACR ( R=0.684, P<0.001), serum creatinine ( R=0.590, P<0.001), course of disease ( R=0.485, P<0.001), triglyceride ( R=0.264, P=0.002), age ( R=0.235, P<0.001), P=0.005), total cholesterol ( R=0.224, P=0.008), systolic pressure ( R=0.194, P=0.022), glomerular filtration rate ( R=-0.540, P<0.001) and BMI ( R=-0.175, P=0.040); There was no correlation with fasting blood glucose, HbA1c, ALT and diastolic blood pressure (all P>0.05). Secondly, the increase of urinary hepcidin level was a risk factor for DKD by binary Logistic regression analysis ( OR=4.147,95% CI: 2.154-7.984, P<0.001). Finally, receiver operating characteristic curve analysis showed that the optimal cut-off point of urinary hepcidin was 6.35 μg/L, with a sensitivity of 0.831 and a specificity of 0.880. Conclusion:Urinary hepcidin increases with the severity of DKD, which may be a biomarker for early diagnosis of DKD.
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