BackgroundDiabetic nephropathy (DN) is one of the most common chronic complications of diabetes mellitus (DM). The changes of α2-macroglobulin (α2-MG), podocalysin (PCX), α-L-fucosidase (AFU), retinol binding protein-4 (RBP-4), cystatin C(CysC) and clinical indicators in patients with or without DN.To explore their role and significance in type 2 diabetes (T2DM) and DN.MethodsA total of 203 T2DM patients admitted to hospital from December 2018 to December 2020 were collected and divided into DN group (115 cases) and NDN group (88 cases). Urine α2-MG, PCX and AFU levels, serum RBP-4 and CysC levels were determined, and other clinical indicators were collected.Results1.Comparison of general data between groups: the levels of CysC, RBP-4, α2-MG/UCr,PCX/UCr and AFU/UCr in DN group were higher than those in NDN group (P<0.05). 2. Comparison of ACR stage and renal function stage of CKD: ①ACR stage: CysC, RBP-4, α2-MG/UCr,PCX/UCr,AFU/UCr increased with the increase of ACR stage(P<0.05). ② Renal function stage of CKD: CysC, RBP-4,α2-MG/UCr, PCX/UCr, AFU/UCr increased with the increase of renal function stage of CKD(P<0.05). 3. Partial correlation analysis after adjusting gender and age: CysC, RBP-4,α2-MG/UCr,PCX/UCr, AFU/UCr were positively correlated with UACR, Scr, Urea, UTP/24h, NLR, but negatively correlated with eGFR(P<0.05). 2.ROC curve: (1) Analysis of single index on DN diagnosis: AUCROC of UACR, eGFR, CysC,RBP-4, α2-MG/UCr,PCX/UCr and AFU/UCr were 0.97, 0.77, 0.80, 0.76, 0.83, 0.86, 0.79, respectively. (2) Analysis of combined indicators for DN diagnosis:AUCROC of α2-MG/UCr+PCX/UCr,α2-MG/UCr+AFU/UCr,α2-MG/UCr+PCX/UCr+AFU/UCr,α2-MG/UCr+PCX/UCr+AFU/UCr were 0.88, 0.88, 0.86, 0.89.Conclusion: 1.α2-MG, PCX and AFU are related to the occurrence and development of DN. 2. RBP-4, CysC, PCX, AFU and α2-MG have better diagnostic value,but UACR has the best diagnostic value. 3.PCX can reflect early renal damage.