Cyclosporine Toxicity and Vascular Endothelial Growth Factor (VEGF).

Abstract

Vascular endothelial growth factor (VEGF) is a potent angiogenic and endothelial cell-specific mitogen. Expression of VEGF mRNA is increased under hypoxia/ischemia conditions. Its role in the setting of clinical kidney transplantation (Tx) is currently under investigation. Majority of works are dealing with gene polymorphisms and/or renal tissue expression. The aim of the study was to evaluate serum VEGF concentrations after kidney Tx and its relationship to graft outcome. Thirty-five adult patients (17 male, 18 female) treated with cyclosporine A or tacrolimus, at least 1 month after Tx and 22 healthy control (17 male, 5 female). Patients with acute rejection or infection were excluded. Serum VEGF (S-VEGF) concentrations were measured by Quantikine Immunoassay, RD Systems. S-VEGF concentrations were significantly higher after Tx than in healthy control (556 ± 463 pg/ml, vs 145 ± 74 pg/ml, p< 0.0001). No correlation was found with age, gender, time after Tx or type of calcineurin inhibitor. However, a significant correlation was found between basaline S-VEGF and S-creatinine (p< 0.05), S-VEGF and S-creatinine six months after Tx (p< 0.01) and between S-VEGF and cyclosporine toxicity defined as a gingival hyperplasia or biopsy proven nephrotoxicity (202 ± 121 pg/ml in stable patients vs 741 ± 436 pg/ml in cyclosporine toxicity group, p< 0.001). During six months of follow up, the kidney graft function was stable in 100% of patients with S-VEGF concentration ≤ 145 pg/ml but only in 50% of patients with S-VEGF concentration > 145 pg/ml (p < 0,05). We conclude that the S-VEGF concentration seems to be a marker of cyclosporine toxicity and prospective graft function deterioration. S-VEGF could be helpful to select patients who would have benefit from an early switch of immunosuppression.