住院糖尿病患者尿视黄醇结合蛋白、β_(2)-微球蛋白与尿白蛋白/肌酐和肾功能的相关性

Urinary retinol binding protein and β_(2)-microglobulin were associated with urinary albumin to creatinine ratio and renal function in hospitalized diabetic patients

目的探讨住院2型糖尿病(T2DM)患者肾小管损伤指标尿视黄醇结合蛋白(RBP)和β_(2)-微球蛋白(β_(2)-MG)与尿白蛋白/肌酐比值(UACR)和肾功能的相关性。方法收集北京大学人民医院住院T2DM患者1030例,比较UACR正常组(<30 mg/g)、微量白蛋白尿组(30~300 mg/g)与大量白蛋白尿组(>300 mg/g)的尿RBP和β_(2)-MG水平;UACR正常患者根据估算的肾小球滤过率(eGFR)分为eGFR下降组(<90 ml·min^(-1)·1.73m^(-2))和eGFR正常组(≥90 ml·min^(-1)·1.73m^(-2)),比较其尿RBP和β_(2)-MG差别。通过多元线性回归分析尿RBP和β_(2)-MG的影响因素。结果(1)随着UACR的升高,3组尿RBP与β_(2)-MG依次升高,尿RBP与β_(2)-MG高于正常范围的比例分别为3.8%、8.5%、39.0%(P<0.001)和12.9%、26.7%、46.8%(P<0.001)。(2)在788例UACR正常者中有12.2%患者eGFR<90 ml·min^(-1)·1.73m^(-2);β_(2)-MG高于正常范围的比例在eGFR下降组中高于eGFR正常组(29.2%比10.7%,P<0.001)。分别以尿RBP和β_(2)-MG的自然对数为因变量,进行多元线性逐步回归分析,显示尿RBP与UACR(β=0.0005,P<0.001)、肌酐(β=0.006,P<0.001)和糖化血红蛋白(HbA1c)(β=0.050,P=0.001)独立相关,尿β_(2)-MG与UACR(β=0.0004,P<0.001)、肌酐(β=0.011,P<0.001)、收缩压(β=0.005,P=0.031)和空腹血糖(β=0.027,P=0.046)独立相关。结论尿RBP与β_(2)-MG在T2DM患者与尿蛋白及肾功能相关,在UACR和eGFR出现异常之前就可出现异常,对UACR和eGFR正常的患者应早期筛查,并积极控制糖尿病肾脏疾病的危险因素。

Objective To explore the associations of urinary retinol binding protein(RBP)andβ_(2)-microglobulin(β_(2)-MG)with urinary albumin to creatinine ratio(UACR)and renal function in hospitalized patients with type 2 diabetes mellitus(T2DM).Methods A total of 1030 Chinese patients with T2DM were included in this study.The subjects were divided into the UACR normal group(<30 mg/g),microalbuminuria group(30-300 mg/g)and macroalbuminuria group(>300 mg/g).Patients with normal UACR were further divided into two groups according to the estimated glomerular filtration rate(eGFR):the eGFR low group(<90 ml·min^(-1)·1.73m^(-2))and the normal eGFR group(≥90 ml·min^(-1)·1.73m^(-2)).Urine RBP andβ_(2)-MG levels among the groups were compared.Multiple linear regression analyses were applied to evaluate risk factors of urine RBP andβ_(2)-MG.Results In all patients(n=1030),urine RBP andβ_(2)-MG increased gradually with the increase of UACR across the three groups,the proportions of abnormal urine RBP(>0.7 mg/L)andβ_(2)-MG(>370μg/L)in these groups were 3.8%,8.5%,39.0%(P<0.001),and 12.9%,26.7%,46.8%(P<0.001),respectively.In the UACR normal group(n=788),12.2%of the patients were with eGFR<90 ml·min^(-1)·1.73m^(-2).The proportion of abnormalβ_(2)-MG(>370μg/L)was higher in the eGFR low group than that in the eGFR normal group(29.2%vs.10.7%,P<0.001).Multivariate linear stepwise regression analyses were performed using natural logarithm of urine RBP orβ_(2)-MG as dependent variable,and showed that urine RBP was independently associated with UACR(β=0.0005,P<0.001),serum creatinine(β=0.006,P<0.001)and glycosylated hemoglobin A1c(β=0.050,P=0.001),andβ_(2)-MG was independently correlated with UACR(β=0.0004,P<0.001),serum creatinine(β=0.011,P<0.001),systolic blood pressure(β=0.005,P=0.031)and fasting blood-glucose(β=0.027,P=0.046).Conclusions Urine RBP andβ_(2)-MG are positively associated with high UACR and impaired renal function in T2DM patients,and these changes could occur before UACR and eGFR turned out to be abnormal.It is recommended that urine RBP andβ_(2)-MG be detected as early as possible to identify diabetic kidney disease in patients with normal UACR and eGFR.