Objective: CD93 is a glycoprotein that is known to enhance phagocytosis. The extracellular portion of CD93 can be enzymatically cleaved and secreted to the serum as a soluble form (sCD93). Diabetic nephropathy (DN) is a well-known inflammatory disease that commonly progresses to end stage renal disease (ESRD) in diabetes. Although albuminuria and estimated glomerular filtration rate (eGFR) is currently used for the diagnosis and the prognostication of DN, the prognostic value of the two parameters is modest at best. Here, we hypothesized that sCD93 would be a new biomarker for DN.
Methods: We registered 97 human subjects with type 2 diabetes and evaluated the association between serum sCD93 and DN. The underlying mechanism of CD93 regulation was elucidated using human umbilical cord endothelial cell (HUVEC) in vitro and diabetic db/db mice in vivo.
Results: The group with higher sCD93 has lower eGFR level and higher prevalence of CKD defined by eGFR. The log(sCD93) was significantly associated with albumin-to-creatinine ratio (ACR) (r=0.229, p=0.028) and the sCD93 level was an independent determinant of ACR and eGFR. The odds ratio of having DN was higher in the high serum sCD93 group even after adjusting for other covariates (adjusted odds ratio 7.283, 95% CI 1.255-42.268, p=0.027). In vitro, CD93 was highly expressed in HUVEC and both CD93 expression and sCD93 secretion was upregulated after LPS stimulation. In db/db mice, sCD93 level was much higher in the peritoneal fluid compared to the db/m mice. The db/db mice showed significantly higher CD93 expression in the renal glomerulus compared to that of the db/m mice suggesting that the elevated sCD93 according to the degree of DN progression might be associated with upregulated expression of CD93 in glomerulus.
Conclusion: Based on these human and rodent data, we conclude that sCD93 could be a candidate molecule associated with DN.
S. Lee: None. H. Park: None. M. Lee: None. A. Choi: None. J. Park: None. C. Ahn: None. S. Lee: None. S. Kang: None.
Korean National Research Foundation (2014R1A1A3051221)