BACKGROUND: Urinary albumin is a kind of urinary protein that leaks out when the glomerular structure is destroyed. It is also an important index for clinical diagnosis of diabetic kidney disease (DKD). However, its diagnostic efficacy has been questioned. The changes of glomerular filtration rate (GFR) and Urinary albumin/creatinine（ACR）are not parallel. Pathological changes of DKD include glomerular and tubular damage, and ACR is not sensitive to changes in tubular function. In the very early stage of DKD, there may be only changes in reabsorption function of renal tubular, glomerular structure has not changed, ACR is still in the normal range. At this stage there is no indication of renal puncture. However, diabetic retinopathy (DR) and diabetic nephropathy have a common pathological basis, and DR can be detected early by non-invasive fundus examination. Although urinary albumin excretion is normal, specific diabetic retinopathy has emerged, suggesting that micro vascular damage caused by diabetes already exists and the earliest DKD changes may have occurred.                      
AIM: To evaluate the diagnostic efficacy of glomerular and tubular function indices in different stages of DKD in patients with type 2 diabetes mellitus. 
MEDTHOD: 1246 patients with type 2 diabetes mellitus (2-DM) admitted to our department from April 1st, 2018 to June 31st, 2019 were selected to integrat the clinical biochemical indexes, urinary albumin/creatinine (ACR), urinary alpha-1 micro globulin/creatinine (A1CR), urinary immunoglobulin G/creatinine (IGUCR), urinary transferrin/creatinine (TRUCR) and fundus examination. Among them, 428 patients underwent 99mTc-EC nuclear medicine to detect effective renal plasma flow (ERPF) and 99mTc-DTPA glomerular filtration rate (GFR). According to ACR level, they were divided into （ACR≤30mg/ gCr）normal albuminuria group (n=266), （30<ACR≤300mg/gCr）micro-albuminuria group (n=114) and (ACR>300mg/gCr)macro-albuminuria group (n=48). The normal group of urinary protein was divided into the control group according to the results of the fundus examination: non-DR with normal albuminuria group (n=210) and DR with normal albuminuria group (n=56). The levels of ACR, A1CR, IGUCR, TRUCR, ERPF, and GFR were compared among groups, and the diagnostic value of the above indexes at different DKD stages was evaluated by ROC curve.  
RESULT: The levels of ACR, A1CR, IGUCR, TRUCR, ERPF, and GFR were significantly different among DKD groups (P < 0.001). ACR, A1CR, IGUCR, and TRUCR increased with the development of clinical stages of nephropathy, while ERPF and GFR decreased with the development of clinical stages of nephropathy. In the normal albuminuria with DR group, the indicators of renal tubular function: A1CR [12.32 (6.88-16.85) mg/gCr], IGUCR [5.70 (4.86-4.86-7.69) mg/gCr] were significantly increased (P < 0.01) compared with the control group wihout DR [6.60 (4.38-10.33) mg/gCr], [3.86 (2.76-6.63) mg/gCr]. However, ERPF [266.79.79 (212.37-306.14) ml/min] in DR group was lower than that of the control group [271.78 (233.25-310.73) ml/min] (P < 0.05).The results of this study are as follows: The indicators of glomerular function: ACR and GFR had no significant difference between the two groups (P > 0.05). The receiver operating characteristic ROC curve analysis showed that the area under the ROC (AUC) of A1CR in type 2 diabetes mellitus with DR and normal urinary protein excretion was 68.2% (P < 0.01) and that of IGUCR, TRUCR and ERPF were 68.1% (P < 0.01), 61.8% (P < 0.01) and 60.5% (P < 0.05). The AUC of ACR and GFR had less than 60% (P > 0.05). ACR, A1CR, IGUCR, TRUCR, ERPF and GFR were all more than 60% in the macroalbuminuria group (P < 0.01).
CONCLUSION: Pathological injuries of DKD include glomerulus and tubules. ACR and GFR representing glomerular functions. There are no significant differences between those normal urinary protein excretion in type 2 DM with DR and that of  the control group without DR, but A1CR, TRUCR and ERPF representing renal tubular functions have changed compared with the control group. The indexes of glomerular and tubular function in macroalbuminuria group were significantly changed compared with those in the control group. It is suggested that the change of renal tubular function maybe earlier in DKD than glomerulus.

Diagnostic value of renal tubular and glomerular function tests in patients with 2-DM at different DKD stages