In this study, the correlation between serum sCD93 concentration and the prevalence of DN was explored, and the results had shown that serum sCD93 concentration was negatively correlated with eGFR and positively correlated with ACR. Furthermore, the risk assessment of renal complications indicated that the H-sCD93 group had a higher risk of DN compared with the L-sCD93 group. The reason could be attributed to the infiltration of inflammatory cells and the release of inflammatory cytokines in DM patients, which was an important pathogenesis mechanism of DN. In fact, CD93 participated in the multistage inflammatory cascade and played an essential role in maintaining the plasma cell production of antibodies. Previous studies had shown that sCD93 was produced under inflammatory conditions and could in turn regulate the inflammatory function of monocytes and macrophages, inducing the differentiation of monocytes into macrophage-like cells. Then, these cells exhibited cell adhesion activation and enhanced phagocytic activity, thereby producing more reactive oxygen species, inflammatory cytokines and profibrotic cytokines, which leaded to a series of related complications.
Considering ACR was the first detectable change in DN, this investigation did the first to explore the relationship between serum sCD93 concentration and the level of microalbuminuria in T2DM patients. The results indicated that the serum sCD93 concentration in T2DM patients was significantly higher than that in the control group, and the serum sCD93 concentration in the L-ACR group was significantly higher than that in the N-ACR and M-ACR groups. The reason might be that sCD93 induced the differentiation of monocytes into macrophage-like cells, enhancing the stimulation of Toll-like receptors and producing proinflammatory cytokines, in particular, transforming growth factor β1 (TGF-β1, increased expression). TGF-β1 played an important role in inflammation and fibrosis together with connective tissue growth factor, platelet-derived growth factor and fibroblast growth factor-2. In addition, sCD93 was also involved in the activation of fibroblasts, leading to increased deposition of extracellular matrix in the interstitium and thicken of the glomerular basement membrane, which might promote podocyte apoptosis and increase glomerular vascular permeability. The above analysis indicated that sCD93 might play an important role in the development of DN. In a word, exploration of the relationship between serum sCD93 concentration and the degree of microalbuminuria provided further evidence of the relationship between sCD93 and the progression of DN, indicating that sCD93 had potential value for monitoring the severity of DN for early intervention and corresponding treatments.
Cr was a traditional clinical indicator for evaluating renal function recommended by Kidney Disease: Improving Global Outcomes (KDIGO). NGAL was a newly discovered small molecular weight secreted protein that was highly expressed in various pathological tissues and cells with abnormal metabolism. The current studies had confirmed that the serum NGAL concentration increased rapidly during acute kidney injury. This study had demonstrated that sCD93 was associated with DN and could reflect DN progression. Based on the analysis of the differences in renal function indicators between the DM and DN groups, the diagnostic efficacy of serum sCD93, NGAL, and Cr alone and in various combinations was further evaluated. The serum sCD93, NGAL, and Cr concentrations in the DN group were higher than those in the DM group, indicating the possibility of using combinations of the 3 indicators as a new diagnostic method for DN. The ROC curve analysis indicated that the serum Cr + NGAL + sCD93 triple test had the highest diagnostic efficiency (AUC = 0.942). On the basis of above data, the combination of 3 indicators provides a new biological means for the diagnosis and treatment of DN.
In summary, this study demonstrated that there was a good correlation between serum sCD93 and traditional markers of DN (eGFR and ACR), and sCD93 could reflect disease progression. Therefore, the inclusion of serum sCD93 as a supplementary diagnostic indicator for DN could improve the diagnostic efficacy for DN and played a role in guiding diagnosis, treatment and early intervention. However, this study had the following limitations. (1) The number of study subjects needed further increase. (2) Only the role of serum sCD93 concentration in DN was explored, but it might also play a role in other CKD models. (3) The eGFR and ACR were used to define DN, but these criteria also had their own limitations in the detection of DN. Therefore, more multicenter, large-sample studies were needed to further reveal the clinical application value of sCD93.