Dynamics of Circulating Endothelial Injury Markers Following Kidney Transplantation

Endotheliopathy is well studied in chronic kidney disease, brought on by the chronic stressors of proinflammatory cytokines and reactive oxygen species. However, the endothelial response to renal transplantation has not been well investigated. This study aimed to evaluate circulating biomarkers of endothelial injury acutely after renal transplantation.

Serum samples were collected from 51 renal transplant patients preoperatively, immediately postoperatively, and at 24 and 72 h postoperatively. Serum was then analyzed for biomarkers of endotheliopathy, including E-selectin, P-selectin, syndecan-1, thrombomodulin, and vascular endothelial growth factors.

Patients were 51% male with a median age of 58 [45, 64] years, and 65% Caucasian. Eighty percent of patients underwent deceased donor kidney transplant (DDKT), and 20% underwent living donor kidney transplant (LDKT). Twenty percent of transplants were complicated by delayed graft function (DGF). Most endothelial biomarkers were highest preoperatively, including P-selectin, matrix metalloproteinase-1, vascular endothelial growth factor (VEGF)-A, VEGF-D, VEGF-R2, and very late antigen (VLA)-4 (P < 0.05). In contrast, platelet endothelial cell adhesion molecule-1 increased, peaking at 72 h postoperatively (P < 0.001). Furthermore, DDKT recipients had higher levels of postoperative thrombomodulin compared with LDKT recipients (P = 0.03), and patients with DGF were more likely to have higher perioperative levels of VEGF-A (P < 0.05).

Most biomarkers of endothelial injury, including adhesion proteins and mediators of endothelial cell migration and survival, decrease acutely after renal transplantation, with a rise in platelet endothelial cell adhesion molecule-1 being the exception. In subgroup analyses, thrombomodulin was elevated in DDKT compared to LDKT recipients, and perioperative VEGF-A elevation was correlated with DGF diagnosis. The etiology of these changes, whether by organ implantation alone or by associated immunosuppression, merits further investigation.