Acute renal allograft rejection is associated with increased levels of vascular endothelial growth factor in the urine

Aim: The purpose of this study was to assess whether measurement of urinary vascular endothelial growth factor (VEGF) could be adopted as a new non-invasive diagnostic tool for acute rejection following renal transplantation. Methods: Urinary concentration of VEGF was determined by an enzyme-linked immunosorbent assay technique in 215 renal allograft recipients and 80 healthy controls. Results: Subjects with acute rejection (n=67) excreted urinary VEGF at a significantly higher level (28.57 +/- 6.21, 95% CI: 16.18-40.97 pg/mu mol creatinine) than those without acute rejection. This included subjects with stable renal function and no abnormal histological findings (n = 119), acute tubular necrosis (n = 15), chronic allograft nephropathy (n = 14) and healthy controls (n = 80). Using a urinary VEGF/creatinine ratio of 3.64 pg/mu mol as the cut-off point, the sensitivity and specificity for diagnosing acute rejection were 85.1 and 74.8%, respectively (P < 0.001). Patients with steroid-resistant acute rejection had significantly greater urinary VEGF concentration than patients with steroid-sensitive acute rejection (42.09 +/- 10.00 vs 9.74 +/- 2.63 pg/mu mol creatinine, P < 0.001). Patients with graft loss after acute rejection had significantly greater urinary VEGF concentration than patients with reversible acute rejection (106.66 +/- 38.60 vs 19.46 +/- 4.13 pg/mu mol creatinine, P = 0.001). Using a urinary VEGF/creatinine ratio of 22.48 pg/mu mol as the cut-off point, the sensitivity and specificity of the prediction to graft loss after acute rejection were 85.7% and 78.3%, respectively (P = 0.001). Conclusion: This study demonstrates that the monitoring of urinary VEGF may be a useful non-invasive approach for the detection of acute rejection. Additionally, urinary VEGF levels were shown to predict the response to anti-rejection therapy and to predict a poor outcome after acute rejection.