Effect of tumor necrosis factor alpha and vascular permeability growth factor on albuminuria in rats

The purposes of this study were to measure the serum levels of vascular permeability growth factor (VPGF) and tumor necrosis factor alpha (TNFalpha) in minimal lesion nephrotic syndrome (MLNS) patients and to assess their effect on albuminuria in rats. Serum for VPGF and TNFalpha was obtained during relapse and remission from 18 MLNS patients. Tumor necrosis factor alpha was infused at the rate of 10 and 20 ng/h and VPGF at the rate of 20 and 40 ng/h for 5 days into the left renal artery of rats. Urinary albumin (24-h collection) was measured prior to infusion and on days 2, 4 and 5. Rats infused with 1% bovine serum albumin served as controls. Serum VPGF and TNFalpha levels in MLNS patients in relapse were not different from those seen during remission. A significant increase in albuminuria was observed on day 4 and 5 only when rats were infused with TNFalpha at the rate of 20 ng/h as compared to the excretion seen in same animals prior to the infusion of cytokine and on days 4 and 5 of normal controls. Neither VPGF nor TNFalpha seems to be the circulating pathogenic cytokine for proteinuria in MLNS. However, TNFalpha may contribute to the increased albuminuria via a paracrine effect at the glomerulus.