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 α (TNFα) in minimal lesion nephrotic syndrome (MLNS) patients and to assess their effect on albuminuria in rats. Serum for VPGF and TNFα was obtained during relapse and remission from 18 MLNS patients. Tumor necrosis factor α 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 TNFα 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 TNFα 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 TNFα seems to be the circulating pathogenic cytokine for proteinuria in MLNS. However, TNFα may contribute to the increased albuminuria via a paracrine effect at the glomerulus. [PUBLICATION ABSTRACT]