Oxidative stress, phosphate and creatinine levels are independently associated with vascular endothelial growth factor levels in patients with chronic renal failure

Elevated VEGF levels has been reported in patients with chronic renal failure (CRF), but the reasons for its higher level in renal insufficiency remain unknown. We assessed VEGF, SOX markers: total peroxide, Cu/Zn superoxide dismutase (Cu/Zn SOD), the levels of autoantibodies against oxidized LDL (OxLDL-Ab), and inflammation markers: high sensitivity C-reactive protein (hs CRP), interleukine-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) in 55 CRF patients and 18 controls. The patients with CRF showed a significant increase in plasma levels of VEGF, markers of inflammation, total peroxide and Cu/Zn SOD levels compared with controls. The strong positive associations were between VEGF and creatinine, urea, phosphate and CaxP product (all p<0.0001), Cu/Zn SOD (p<0.001) and hs CRP levels (p<0.01). VEGF showed a strong inverse relationship with eGFR (p<0.0001). In multiple regression analysis increased Cu/Zn SOD, phosphate and creatinine levels were found to be independent factors affecting VEGF. This study documented significant elevation in plasma values of VEGF in patients with CRF, which appears early during the progression of renal insufficiency. Increased oxidative stress, phosphate levels and impaired elimination by kidney were the main factors affecting the plasma levels of this growth factor in CRF patients.