Vascular Permeability Factor (VPF) in Children with Proteinuric Renal Disease. † 1691

VPF, also known as vascular endothelial growth factor, profoundly enhances microvascular permeability. VPF protein (pro) and mRNA have been localized to glomerular epithelial cells and VPF has been hypothesized to play a role in pathologic proteinuria. Using a sensitive and specific non-competitive immunoassay (Yeo, Clin Chem, 1992), we quantitated urine (U) VPF and the degree of proteinuria (U_pro/cr) in 270 pediatric pts. Pts were divided into 4 groups (grps): 1) Well children with no known chronic medical problems (n=22); 2) Pts with isolated microhematuria or urinary tract infections unassociated with proteinuria (n=72); 3) Pts with persistent proteinuric renal disease (U_pro/cr >0.2) exclusive of minimal change disease (MCD) or focal glomerulosclerosis (FSGS) (n=97); 4) Pts with nephrotic syndrome (NS) secondary to MCD or FSGS (n=79). Mean ± SEM U_pro/cr was normal (≤ 0.2) in grps 1 (0.08 ± 0.01) and 2(0.20 ± 0.05) but significantly elevated in grps 3 (0.90 ± 0.12) and 4 (5.20 ± 1.26). Despite these differences, U VPF levels did not differ among the grps (3.21 ± 0.30, 4.26 ± 0.82, 5.59 ± 1.25, and 4.96 ± 0.63 picomoles/L in grps 1, 2, 3 and 4 respectively; p=0.33). A significant correlation did exist, however, between U VPF and the degree of proteinuria in grp 4 pts with MCD or FSGS and U_pro/cr >1(R²=0.40; p<0.001). In comparison, in grp 3 pts with a U_pro/cr > 1, U VPF and degree of proteinuria were unrelated(R²<0.001; p=0.98). Moreover, in 39 pts from grp 3 with biopsy documented proliferative glomerulonephritis (prolif GN) such as lupus, IgA, or membranoproliferative disease, U VPF and U_pro/cr >1 were similarly unrelated (R²=0.07; p=0.4) In 44 pts (21 from grp 2 and 23 from grps 3 and 4), concomitant serum VPF assays were performed. There was no difference in mean serum VPF levels (3.4 ± 1.2 vs. 3.1 ± 1.0 picomoles/L; p=0.84) and serum and U VPF levels were unrelated (R²=0.003; p=0.7). We conclude that: 1) U VPF levels correlate with the degree of proteinuria in children with NS; 2) U VPF levels do not simply vary coordinately with proteinuria in other pediatric proteinuric renal diseases including prolif GN; and 3) Serum and U VPF levels vary independently. We speculate that VPF plays a role in the proteinuria of MCD and FSGS in children. In contrast to these diseases of epithelial cells, VPF does not play a role in renal diseases with evidence of immune complex deposition.