肾小管及肾小球标志物在2型糖尿病患者不同肾损伤阶段诊断价值的研究

Diagnostic value of renal tubular and glomerular markers in different stages of renal injury in patients with type 2 diabetes

目的探讨肾小管及肾小球相关标志物在2型糖尿病(type 2 diabetes mellitus,T2DM)患者不同肾损伤阶段的诊断价值。方法选取于2018年4月1日至2019年10月31日入住首都医科大学附属北京同仁医院内分泌科的T2DM患者272例,完善临床生化指标及尿蛋白四项:尿微量白蛋白/肌酐(urinary albumin to creatinine ratio,ACR)、α1-微球蛋白/肌酐(urinary α1-microglobulin to creatinine ratio,UA1CR)、免疫球蛋白G/肌酐(urinary immunoglobulin G to creatinine ratio,UIGG)、转铁蛋白/肌酐(urinary transferrin to creatinine ratio,UTRF);进行眼底照相、核医学99mTc-EC检测肾有效血浆流量(effective renal plasma flow,ERPF)和99mTc-DTPA检测肾小球滤过率(glomerular filtration rate,GFR)。根据ACR和眼底检查结果分为4组:正常蛋白尿无糖尿病视网膜病变(diabetic retinopathy,DR)132例,即对照组(ACR≤30 mg/g);正常蛋白尿合并DR 32例,为糖尿病肾病(diabetic kidney disease,DKD)前期组;微量蛋白尿组78例(30<ACR≤300 mg/g)和大量蛋白尿组30例(ACR>300 mg/g)。比较四组间尿蛋白四项和ERPF、GFR的水平,通过受试者工作特征(receiver operating characteristic,ROC)曲线评价上述各指标在不同肾损伤阶段的诊断价值。结果尿蛋白四项和ERPF、GFR的水平在不同组间差异有统计学意义(P<0.05)。在尿蛋白正常组中,DR组中肾小管功能标志物UA1CR较对照组明显升高(P<0.01);肾小球功能标志物ACR、UTRF和GFR在两组间差异无统计学意义(P>0.05),DR组UIGG较对照组升高(P<0.01)。在微量蛋白尿组和大量蛋白尿组,尿蛋白四项随肾损伤程度增加而增加,而ERPF和GFR随肾损伤程度增加而降低。ROC曲线分析显示,在尿蛋白排出正常的T2DM患者中合并DR组中肾小管功能标志物UA1CR和ERPF的曲线下面积(area under the curve,AUC)分别为68.2%(P<0.01)和60.5%(P<0.05),而肾小球功能标志物ACR和GFR的AUC均小于60%,差异无统计学意义(P>0.05)。尿蛋白四项及GFR在微量和大量蛋白尿组的AUC均大于60%(P<0.05),ERPF在大量蛋白尿组AUC为67.2%(P<0.05)。结论T2DM极早期微血管改变即ACR正常仅有DR时,肾小管标志物UA1CR先于肾小球标志物ACR和GFR发生变化。肾损伤早期,肾小管标志物诊断效能优于肾小球;肾损伤后期,肾小球标志物诊断效能优于肾小管。提示DKD肾小管功能的改变可能早于肾小球。

Objective To investigate the diagnostic value of renal tubular and glomerular markers in type 2 diabetes patients at different stages of renal injury.Methods Totally 272 patients with type 2 diabetes mellitus(T2DM)admitted to the Department of Endocrinology,Beijing Tongren Hospital,Capital Medical University,from April 1,2018 to October 31,2019 were enrolled,to improve the clinical biochemical indicators and four items of urine protein:urinary microalbumin/creatinine(ACR),α1-microglobulin/creatinine(UA1CR),urinary immunoglobulin G to creatinine ratio(UIGG),transferrin/creatinine(UTRF);Perform fundus photography,nuclear medicine 99mTc-EC to measure renal effective plasma flow(ERPF),and 99mTc-DTPA to measure glomerular filtration rate(GFR).According to ACR,there were 164 cases in the normal proteinuria group,78 cases in the microalbuminuria group,and 30 cases in the macroproteinuria group.The normal proteinuria group was divided into control group[132 cases without diabetes retinopathy(DR)]and diabetic kidney disease(DKD)early stage group(32 cases with DR)according to fundus examination.Compare the levels of urinary protein,ERPF,and GFR among four groups,and evaluate the diagnostic value of the above indicators in different stages of renal injury through ROC curves.Results There were statistical differences(P<0.05)in the levels of urinary protein,ERPF,and GFR among different groups.In the normal urine protein group,the markers representing renal tubular function in the DR group were significantly higher in UA1CR compared to the control group(P<0.01);The markers representing glomerular function,ACR,UTRF,and GFR,showed no significant statistical difference between the two groups(P>0.05),while UIGG increased compared to the control group(P<0.01).In the group of microalbuminuria and the group of macroproteinuria,the four urinary protein levels increased with the degree of renal injury,while ERPF and GFR decreased with the degree of renal injury.ROC curve analysis showed that the area under curve(AUC)of UA1CR and ERPF,the markers reflecting renal tubular function,in type 2 diabetes patients with DR who had normal urinary protein excretion,were 68.2%(P<0.01)and 60.5%(P<0.05),respectively,while the AUC of classic ACR and GFR reflecting glomerular function were less than 60%(P>0.05)without statistical significance.The AUC of urinary protein and GFR in both trace and high proteinuria groups was greater than 60%(P<0.05),while the AUC of ERPF in high proteinuria group was 67.2%(P<0.05).Conclusion In the very early stage of T2DM,when ACR is normal and only DR is present,renal tubular markers UA1CR and ERPF undergo changes before glomerular markers ACR and GFR.In the early stage of renal injury,the diagnostic efficacy of renal tubular markers is superior to that of glomeruli;In the later stage of renal injury,the diagnostic efficacy of glomerular markers is due to the renal tubules.The changes in renal tubular function in DKD may occur earlier than in the glomerulus.