Urinary excretion of vascular endothelial growth factor is increased in children with reflux nephropathy

Background: We determined the urinary levels of vascular endothelial growth factor (VEGF) in patients with reflux nephropathy to elucidate its clinical significance as a predictor of the development of renal damage. Patients and Methods: Seventy-two patients (47 boys and 25 girls) aged 10-18 years with reflux nephropathy were studied. Vesicoureteral reflux was resolved surgically in all cases at least 2 years before enrollment. Urinary VEGF, α₁-microglobulin and albumin levels were determined using morning spot urine samples. Plasma VEGF, serum creatinine and β₂-microglobulin levels were measured simultaneously. The severity of renal scarring and right and left kidney function were assessed by ^99mTc dimercaptosuccinic acid renal scan. Results: No significant correlation was found between the plasma and urinary VEGF levels. Urinary VEGF increased significantly with the increase in severity of renal scarring (p < 0.0001). Urinary VEGF levels correlated significantly with serum β₂-microglobulin (p < 0.002) and urinary α₁- microglobulin (p < 0.03). No significant correlation of urinary VEGF levels with serum creatinine and urinary albumin levels was found. Nearly 60% of the patients with elevated urinary VEGF had normal levels of serum β₂-microglobulin and/or urinary α₁- miocroglobulin. Conclusions: Urinary VEGF level appears to reflect its production in the kidney. Since urinary VEGF shows a propensity to elevate before the increase in serum β₂-microglobulin and/or urinary α₁-microglobulin, urinary VEGF may serve as an early indicator of the development of reflux nephropathy.