| Objective:To analyze the changes of α2-macroglobulin(α2-MG),podocalysin(PCX),α-L-fucosidase(AFU),retinol binding protein-4(RBP-4),cystatin C(CysC)and some clinical indexes in patients with type 2 diabetes mellitus(T2DM)with and without diabetic kidney disease(DKD),and to explore their impact and significance in T2DM and DKD.Methods:The clinical data and serum and urine samples of T2DM patients admitted to our hospital from December 2018 to December 2020 were collected.The 239 T2DM patients with serum samples were divided into DKD group(n=124)and NDKD group(n=115).The 203 T2DM patients with urine samples were divided into DKD group(n=115)and NDKD group(n=88).Serum samples and urine samples were both retained in some patients.The 107 patients in this part are divided into DKD group(n=84)and NDKD group(n=23).Enzyme linked immunosorbent assay(ELISA)was used to determine the levels of α2-MG and PCX in serum,α2-MG,PCX and AFU in urine,chemiluminescence method to determine serum AFU(serum α2-MG,PCX,AFU levels were expressed by B-,urine was expressed by U-),serum RBP-4 and CysC levels were determined by immunoturbidimetry,and relevant clinical indexes were collected and determined.Compare the general clinical data between groups and the stages of ACR and the renal function stages of CKD,analyze the variables,do ROC curve to determine the diagnostic cut-off point,sensitivity and specificity of each index in DKD,and clarify the diagnostic value of these indexes in DKD.Results:1.Comparison of general information between groups:1.1 Serum group:The age,proportion of hypertension,course of disease,FPG,NLR,hs-CRP,TG,Urea,CysC,RBP-4,Scr,UACR,UTP/24h,B-α2-MG and B-AFU in DKD group were higher than those in NDKD group,while HDL-C,eGFR and B-PCX were lower than those in NDKD group,the difference were statistically significant(P<0.05).1.2 Urine group:The age,proportion of hypertension,course of disease,NLR,hs-CRP,TC,Urea,CysC,RBP-4,Scr,UACR,UTP/24h,U-α2-MG/UCr,U-PCX/UCr,U-AFU/UCr in DKD group were higher than those in NDKD group,while eGFR was lower than those in NDKD group,the difference were statistically significant(P<0.05).2.Comparison of ACR stage and the renal function stage of CKD:2.1Serum group:①ACR stage:B-α2-MG,B-PCX and B-AFU in stage A3 were higher than those in stage A1,and CysC and RBP-4 in stage A3 were higher than those in stage A1 and A2,the difference were statistically significant(P<0.05).②The renal function stage of CKD:there was no significant difference in B-α2-MG,B-PCX and B-AFU among the three groups(P>0.05);CysC in stage G4-5 and stage G3 was higher than that in stage G1 and stage G2,and RBP-4 was higher than that of the other three groups in stage G4-5,followed by stage G3,the difference were statistically significant(P<0.05).2.2 Urine group:①ACR stage:the levels of U-α2-MG/UCr,U-AFU/UCr and CysC in stage A3 were higher than those in stage A1 and stage A2,and the levels of U-PCX/UCr and RBP-4 were the highest in stage A3,the second in stage A2 and the lowest in stage Al,the difference were statistically significant(P<0.05)(2)The renal function stage of CKD:the levels of U-α2-MG/UCr,U-PCX/UCr and U-AFU/UCr were the highest in stage G4-5,followed by stage G3.The level of CysC in stage G4-5 was the highest,stage G3 was the second,and stage 1 was the lowest.The level of RBP-4 in stage G4-5 was significantly higher than that in the other three groups,the difference were statistically significant(P<0.05).3.Partial correlation analyswas after adjusting gender and age:3.1 Serum group:①CysC was positively correlated with UACR,RBP-4,B-α2-MG,B-PCX,Scr,Urea,UTP/24h,NLR,hs-CRP and negatively correlated with eGFR(P<0.05);②RBP-4 was positively correlated with UACR,CysC,B-α2-MG,B-PCX,B-AFU,Scr,Urea,UTP/24h,NLR and negatively correlated with eGFR(P<0.05);③B-α2-MG was positively correlated with UACR,RBP-4,CysC,B-AFU,Scr,Urea,UTP/24h,hs-CRP and negatively correlated with eGFR(P<0.05);④B-PCX was positively correlated with UACR,RBP-4,CysC,Scr,UTP/24h and negatively correlated with eGFR(P<0.05);⑤B-AFU was positively correlated with UACR、RBP-4 and B-α2-MG(P<0.05).3.2 Urine group:①CysC was positively correlated with UACR,RBP-4,U-α2-MG/UCr,U-PCX/UCr,U-AFU/UCr,Scr,Urea,UTP/24h,NLR and negatively correlated with eGFR(P<0.05);②RBP-4 was positively correlated with UACR,CysC,U-α2-MG/UCr,U-PCX/UCr,U-AFU/UCr,Scr,Urea,UTP/24h,NLR and negatively correlated with eGFR(P<0.05);③U-α2-MG/UCr was positively correlated with UACR,CysC,RBP-4,U-PCX/UCr,U-AFU/UCr,Scr,Urea,UTP/24h,NLR and negatively correlated with eGFR(P<0.05);④U-PCX/UCr was positively correlated with UACR,CysC,RBP-4,U-α2-MG/UCr,U-AFU/UCr,Scr,Urea,UTP/24h、NLR and negatively correlated with eGFR(P<0.05);⑤U-AFU/UCr was positively correlated with UACR,CysC,RBP-4,U-α2-MG/UCr,U-PCX/UCr,Scr,Urea,UTP/24h and NLR,but negatively correlated with eGFR(P<0.05).4.ROC curve:4.1 Serum group:Taking eGFR<60ml·min-1·1.73m-2 or UACR≥30mg/g as the diagnostic cutoff value of DKD,the results of ROC curve show that:(1)Analysis of single index for DKD diagnosis:①The diagnostic cutoff value of UACR was 30.4mg/g.When UACR>30.4mg/g,the sensitivity and specificity of diagnosing DKD were 94%and 100%,respectively.The AUCROC was 0.97;②The diagnostic cutoff value of eGFR was 72.58ml·min-1·1.73m-2.When eGFR<72.58 ml·min-1·1.73m-2,the sensitivity and specificity of diagnosing DKD were 98%and 57%,respectively.The AUCROC was 0.75;③The diagnostic cutoff value of CysC was 0.91mg/L.When CysC>0.91mg/L,the sensitivity and specificity of diagnosing DKD were 60%and 93%,respectively.The AUCROC was 0.78;④The diagnostic cutoff value of RBP-4 was 50.9 mg/L.When RBP-4>50.9mg/L,the sensitivity and specificity of diagnosing DKD were 51%and 87%,respectively.The AUCROC was 0.70;⑤The diagnostic cutoff value of B-α2-MG was 1.38mg/L.When B-α2-MG>1.38 mg/L,the sensitivity and specificity of diagnosing DKD were 46%and 72%,respectively.The AUCROC was 0.60;⑥The diagnostic cutoff value of B-PCX was 3.59ng/mL.When B-PCX<3.59ng/mL,the sensitivity and specificity of diagnosing DKD were 73%and 34%,respectively.The AUCROC was 0.59;⑦The diagnostic cutoff value of B-AFU was 19U/L.When B-AFU>19U/L,the sensitivity and specificity of diagnosing DKD were 73%and 44%,respectively.The AUCROC was 0.58;(2)Analysis of combined indicators for the diagnosis of DKD:①The sensitivity and specificity of B-α2-MG+B-PCX+B-AFU in the diagnosis of DKD were 73%and 56%,respectively.The AUCROC was 0.67;②The sensitivity and specificity of B-α2-MG+B-PCX+B-AFU+RBP-4 in the diagnosis of DKD were 49%and 96%,respectively.The AUCROC was 0.74;③The sensitivity and specificity of B-α2-MG+B-PCX+B-AFU+CysC in the diagnosis of DKD were 60%and 95%,respectively.The AUCROC was 0.82;④The sensitivity and specificity of B-α2-MG+B-PCX+B-AFU+RBP-4+CysC in the diagnosis of DKD were 67%and 90%,resp-ectively.The AUCROC was 0.83;⑤The sensitivity and specificity of CysC+UACR in the diagnosis of DKD were 91%and 99%,respectively.The AUCROC was 0.99.4.2Urine group:Taking eGFR<60ml·min-1·1.73m-2 or UACR≥30mg/g as the diagnostic cutoff value of DKD,the results of ROC curve show that:(1)Analysis of single index for DKD diagnosis:①The diagnostic cutoff value of UACR was 29.5mg/g.When UACR>29.5mg/g,the sensitivity and specificity of diagnosing DKD were 95%and 98%,respectively.The AUCROC was 0.97;②The diagnostic cutoff value of eGFR was 74.41ml·min-1·1.73m-2.When eGFR<74.41 ml·min-1·1.73m-2,the sensitivity and specificity of diagnosing DKD were 96%and 58%,respectively.The AUCROC was 0.77;③The diagnostic cutoff value of CysC was 1.1lmg/L.When CysC>1.11mg/L,the sensitivity and specificity of diagnosing DKD were 54%and 99%,respectively.The AUCROC was 0.80;④The diagnostic cutoff value of RBP-4 was 56.90 mg/L.When RBP-4>56.90mg/L,the sensitivity and specificity of diagnosing DKD were 45%and 98%,respectively.The AUCROC was 0.76;⑤The diagnostic cutoff value of U-α2-MG/UCr was 3.90 mg/g.When U-α2-MG/UCr>3.90 mg/g,the sensitivity and specificity of diagnosing DKD were 55%and 99%,respectively.The AUCROC was 0.83;⑥The diagnostic cutoff value of U-PCX/UCr was 4.81ug/g.When U-PCX/UCr>4.81ug/g,the sensitivity and specificity of diagnosing DKD were 84%and 75%,respectively.The AUCROC was 0.86;⑦The diagnostic cut-off value of U-AFU/UCr was 0.18nmol/g.When U-AFU/UCr>0.18nmol/g,the sensitivity and specificity of diagnosing DKD were 63%and 92%,respectively.The AUCROC was 0.79;(2)Analysis of combined indicators for the diagnosis of DKD:①The sensitivity and specificity of U-α2-MG/UCr+U-PCX/UCr in the diagnosis of DKD were 86%and 76%,respectively.The AUCROC was 0.88;②The sensitivity and specificity of U-PCX/UCr+U-AFU/UCr in the diagnosis of DKD were 75%and 86%,respectively.The AUCROC was 0.88;③The sensitivity and specificity of U-α2-MG/UCr+U-AFU/UCr in the diagnosis of DKD were 68%and 90%,respectively.The AUCROC was 0.86;④The sensitivity and specificity of U-α2-MG/UCr+U-PCX/UCr+U-AFU/UCr in the diagnosis of DKD were 89%and 75%,respectively.The AUCROC was 0.89;5.Correlation of α2-MG,PCX and AFU in serum and urine:U-α2-MG/UCr and B-α2-MG in the DKD group were positively correlated(P<0.05),and the remaining indicators were wirelessly correlated(P>0.05).Conclusions:1.The levels of α2-MG,PCX and AFU in serum and urine in DKD group were higher than those in NDKD group,which were related to renal function indexes such as UACR,eGFR,RBP-4,CysC,Scr,Urea and UTP/24h.Like the traditional risk factors such as age,course of disease,hypertension and lipid metabolism disorder,they were involved in the occurrence and development of DKD,and inflammation was also involved in the pathological process of DKD.2.RBP-4,CysC in serum and PCX,AFU,α2-MG in urine have better diagnostic value,but the value of PCX,AFU and α2-MG in blood in the diagnosis of DKD is limited.3.Theα2-MG in serum was positively correlated with α2-MG in urine,which was related to the progress of renal function.4.PCX in urine can reflect early renal damage.5.The diagnostic value of PCX,AFU,α2-MG,RBP-4 and CysC is lower than that of UACR. |
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