关键词: 糖尿病肾病, 肾小管标志物, α1-微球蛋白, 肾有效血浆流量, ROC曲线下面积

Abstract: 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.

Key words: renal tubular biomarkers, diabetes nephropathy, α1-microglobulin, renal effective plasma flow, area under the receiver operating characteristic curve