E.R. Becker1, G.C. Wetmore1, A.D. Price1, R.R. Schuster1, J.R. Merola2, R.C. Quillin1, M.D. Goodman1 1University Of Cincinnati, Department Of Surgery, Cincinnati, OH, USA 2Cincinnati Children’s Hospital Medical Center, Department Of Surgery, Cincinnati, OH, USA
Introduction: Inflammation causing endothelial injury and coagulopathy has been described in various disease populations, but is not well understood within the field of solid organ transplantation. This study aimed to evaluate circulating biomarkers of endothelial injury acutely following renal transplantation.
Methods: Serum samples were collected from 10/2023 to 04/2024 from 20 renal transplant patients preoperatively, immediately postoperatively, and at 24 and 72 hours postoperatively. Serum was analyzed for 12 markers of endotheliopathy including angiopoietin 1, E-selectin, P-selectin, syndecan-1, thrombomodulin, and vascular endothelial growth factors. A retrospective chart review was completed to collect demographics, etiology of end stage renal disease (ESRD), perioperative creatinine and urine output.
Results: Patients were 50% male (n=10), with a median age of 50.5 years [40, 57.75], and 70% White (n=14). The most common cause of ESRD was diabetes and/or hypertension (n=12, 60%) followed by IgA nephropathy (n=3, 15%). 45% of patients were on peritoneal dialysis (n=9), 40% were on hemodialysis (n=8), and 15% were preemptive transplants (n=3), with a median of 2 years [0.625, 4] on dialysis. 80% underwent deceased donor (n=16) and 20% underwent living donor kidney transplant (n=4). Postoperatively, creatinine decreased (7.7mg/dL preoperatively to 4.6mg/dL 72 hr postoperatively, p=0.02) and urine output increased (0.45mL/kg/hr preoperatively to 1.56mL/kg/hr 72 hr postoperatively, p<0.001). 20% of transplants were complicated by delayed graft function (n=4) without an effect on biomarkers. As for markers of endotheliopathy, P-selectin decreased from preoperative (497,984±485,425 pg/mL) to 24 hr (345,870±240,763 pg/mL, p=0.003) and 72 hr (266,036±227,255 pg/mL, p=0.006) postoperative levels. MMP-1 decreased from preoperative to 24 hr postoperative levels (201±151 vs. 135±92 pg/mL, p=0.03). VEGF-A decreased between all four time points consecutively (5,472±6,795, 3,966±5,527, 3,245±5,003, and 2,841±4,952 pg/mL, p<0.001). VEGF-R2 decreased between preoperative and all post operative levels (14,512±5,386, 13,099±5,107, 11,686±4,527, and 11,936±3,606 pg/mL, p<0.006). Finally, VLA-4 demonstrated a stepwise decrease over the four timepoints (470±283, 381±164, 380±242, 291±153 pg/mL, p<0.04) (Figure).
Conclusion: Serum biomarkers of endothelial injury, including adhesion proteins and mediators of angiogenesis, decrease acutely following renal transplantation. The etiology of these beneficial changes, whether by organ implantation alone or by associated immunosuppression, merit further investigation.