Abstract 1123 Poster Session IV, Tuesday, 5/4 (poster 255)

Background. The angiogenic cytokine vascular endothelial growth factor (VEGF) is elevated in the vitreous during proliferative retinopathies (PR), including retinopathy of prematurity (ROP). Angiogenic factors such as VEGF are often elevated in the urine of subjects with active cancers, even if the malignancy is distant from the genitourinary tract. If increases in vitreal VEGF were mirrored in the urine of patients with ROP or other PR, urinary VEGF determinations might be useful for the better targeting of eye examinations in such patients.

Methods. In preliminary investigations, fullterm infants <24 hours old (n=3), preterm infants (<35 weeks gestation at birth) with respiratory distress syndrome (n=3), normal 4-week-old preterm infants without ROP (n=3), preterm infants with ≥12 clock hours of Stage 2-3 ROP (n=3), preterm infants with nephrocalcinosis (NC)(n=3) and one preterm infant with ROP and NC had urine specimens collected. In order to obtain a population lacking the complicating factors of gestational and postnatal age, adults with absent (n=16), moderate (n=8) or severe (requiring laser photocoagulation, n=18) PR were also assessed. VEGF was measured in urine by enzyme linked immunosorbent assay and normalized to urinary creatinine concentration.

Results. Among infants, both ROP and NC were associated with elevated urinary VEGF. Infants with ROP had higher urinary VEGF than control preterm infants without ROP or NC (1748 ± 183 vs. 1164 ± 464 pg VEGF/mg Cr, p=0.046), but the differing gestational and postnatal ages and the confounding effect of NC made interpretation of the results unclear. Among the adults, controls were younger (45 ± 10 vs. 59 ± 13 years) than subjects with PR. Seven of 16 adult controls and 15/26 adults with PR were male. Six of 16 adult controls and 24/26 adults with PR had diabetes mellitus. None of the 16 adult controls, but 11/26 adults with PR had >200 mg VEGF/mg Cr in the urine (p=0.003). This cut-off made elevated urinary VEGF 100% specific for PR, but only 42% sensitive (area under ROC curve 66%). Among adults, urinary VEGF was also moderately correlated with urinary protein excretion (r2=0.24). Correction of VEGF values for urinary protein abrogated any correlation of urinary VEGF with PR.

Conclusions. Urinary levels of VEGF are associated with the presence of PR in both infants and adults, but this relationship is confounded by concurrent renal diseases that may cause proteinuria in patients most at risk for PR. In addition, the insensitivity of the test precludes its use as a screening tool to avoid eye examinations, since many patients with active retinopathy would be missed by a negative test.