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

Abstract

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. Urinary concentration of VEGF was determined by an enzyme-linked immunosorbent assay technique in 215 renal allograft recipients and 80 healthy controls. 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/mumol 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/micromol 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/micromol 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/micromol creatinine, P=0.001). Using a urinary VEGF/creatinine ratio of 22.48 pg/micromol 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). 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.