Abstract:

Objective To investigate the correlation between serum cathepsin S（Cat S），beta 2-microglobulin（β2-MG），soluble urokinase-type plasminogen activator receptor（suPAR） and the severity of diabetic nephropathy（DN）. Methods A total of 140 patients with DN（DN group），162 patients with simple type 2 diabetes mellitus（T2DM）（T2DM group）and 140 healthy subjects（healthy control group）in Shijiazhuang Maternal and Child Health Hospital from November 2020 to November 2023 were enrolled. The clinical data and laboratory determination results were collected. According to the scores of interstitial fibrosis and tubular atrophy（IFTA），DN patients were classified into mild group（43 cases，with an IFTA score of 0），moderate group（35 cases，with an IFTA score of 1），slightly severe group（31 cases，with an IFTA score of 2）and severe group（31 cases，with an IFTA score of 3）. Logistic regression analysis was used to evaluate the influencing factors of severe DN incidence，and Spearman correlation analysis was applied to analyze the correlation between each index and the severity of DN. The efficacy of each index in diagnosing DN was evaluated by receiver operating characteristic（ROC）curve. Results The serum levels of Cat S，β2-MG and suPAR in DN group，T2DM group and healthy control group were decreased sequentially（P<0.001）. There was no statistical significance in various clinical data among the 3 groups（P>0.05）. Course of T2DM disease and the serum levels of glycated hemoglobin A1c（HbA1c），Cat S，β2-MG and suPAR in mild group，moderate group，slightly severe group and severe group were all increased sequentially（P<0.001）. The number of hypertension patients in severe group was higher than those in mild group，moderate group and slightly severe group（P<0.05）. There was no statistical significance in the other indicators among the 3 groups（P>0.05）. The levels of serum Cat S，β2-MG，suPAR，HbA1c，disease course and hypertension were all positively correlated with the severity of DN（r=0.656，0.782，0.849，0.751，0.705 and 0.817，P<0.001）. Course of T2DM disease，hypertension and elevated HbA1c，serum Cat S，β2-MG and suPAR levels were risk factors for severe DN（P<0.05）. The areas under curves（AUC）of serum Cat S，β2-MG and suPAR single and combined determinations for the diagnosis of severe DN were 0.815，0.851，0.878 and 0.979，respectively. Conclusions The serum levels of Cat S，β2-MG and suPAR in DN patients are positively correlated with DN severity，which can be used as indicators for judging the condition of DN.

Key words: Cathepsin S, Beta 2-microglobulin, Soluble urokinase-type plasminogen activator receptor, Diabetic nephropathy